MXPA99000453A - Active compounds receivers of cal - Google Patents

Abstract

Novel active calcium receptor compounds represented by the following general formula: AR1- [CR1R2] pX [CR3R4] q- [CR5R6] -NR7- [CR8R9] Ar2, wherein Ar1 is selected from the group consisting of aryl, heteroaryl, bis (arylmethyl) amino, bis (heteroaryl-methyl) amino and arylmethyl (heteroarylmethyl) amino; X is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl and amino: R1, R2, R3, R4, R5, R6 , R7, R8 and R9 represents, for example, each hydrogen or alkyl, Ar2 is selected from the group consisting of aryl or heteroaryl, p is an integer from 0 to 6, and q is an integer from 0 to

Description

ACTIVE COMPOUNDS CALCIUM RECEPTORS FIELD OF THE INVENTION This invention relates to the design, development, composition and use of novel molecules, capable of modulating the activity of the inorganic ion receptor.

BACKGROUND OF THE INVENTION Certain body cells respond not only to chemical signals, but also to ions such as extracellular calcium ions (Ca). Changes in the concentration of extracellular Ca (hereafter "[Ca]") alter the functional responses of these cells. One of these specialized cells is the parathyroid cell that secretes the parathyroid hormone (HPT). The HPT is the main endocrine factor that regulates the homeostasis of Ca in the blood and extracellular fluids. The HPT, acting on bone and kidney cells increases the level * of Ca2 + in the blood. This increase in [Ca2 +] then acts as a negative feedback signal, which depresses the secretion of PTH. The reciprocal relationship between [Ca] and the secretion of HPT forms the essential mechanism that maintains the homeostasis of Ca in the body. The extracellular Ca 2 acts directly on the parathyroid cells to regulate the secretion of PTH. The existence of a protein on the surface of parathyroid cells, which detects changes in [Ca2 +], has been confirmed. Brown and co-authors, 366 Nature 574, 1993. In parathyroid cells, this protein acts as a receptor for Ca + ("the calcium receptor") and detects changes in [Ca2 +], and to initiate a functional cellular response, secretion of HPT. The extracellular Ca can exert effects on diverse cellular functions, summarized in Nemeth and coauthors, 11 Cell Calcium 319, 1990. The role of extracellular Ca2 + in parafollicular cells (C cells) and in parathyroid cells is discussed in Nemeth, 11 Cell Calcium 323, 1990. It has been shown that these cells express a similar Ca receptor. Brown and co-authors, 366 Nature 574, 1993; Mithal and coauthors, 9 supplement 1 J. Bone and Mineral Res. S282, 1994; Rogers and co-authors, 9 supplement 1, J. Bone and Mineral Res. S409, 1994; Garret and co-authors, 9 supplement 1 J. Bone and Mineral Res. S 409, 1994. The role of extracellular Ca2 + on bone osteoclasts is discussed by Zaidi 10 Bioscience Reports 493, 1990. In addition to keratinocytes, juxtaglomerular cells, trophoblasts, beta-pancreatic cells and fat / fat cells all respond to increases in extracellular calcium, which probably reflects the activation of calcium receptors on these cells.

The ability of various compounds to reproduce extracellular in vitro is discussed by Nemeth and co-authors (spermine and spermidine) in "Calcium-Binding Proteins in Health and Disease," 1987, Academic Press Inc., pages 33-35; Brown and co-authors (e.g., neomycin) 128 Endocrinology 3047, 1991; Chen and co-authors (diltiazem and its analog, TA-3090) 5J Bone and Mineral Res. 581, 1990; and Zaidi and co-authors (verapamil) 167 Biochem. Biophys. Res. Commun. 807, 1990. 'Nemeth and co-inventors PCT / US93 / 01642, international publication number WO 94/18959; Nemeth and co-inventors, PCT / US92 / 07175, international publication number WO93 / 04373; Nemeth and co-inventors, PCT / US94 / 12117, International Publication Number WO 95/11221 and Nemeth and co-Inventors, PCT / US95 / 13704 International Publication Number WO 96/12697, describe various compounds that can modulate the effect of an inorganic ion on a cell having an inorganic ion receptor, preferably modulating the effects of calcium on a calcium receptor. It is the object of the present invention to provide a novel inorganic ion receptor active compound having a structure different from that of the compounds described above.

DESCRIPTION OF THE INVENTION The present invention incorporates molecules that can modulate one or more activities of an inorganic ion receptor. Preferably, the molecule can reproduce or mimic, or block the effect of extracellular Ca2 + on the calcium receptor. The preferable use of said molecules is for treating diseases or disorders by altering the activity of the inorganic ion receptor, preferably the activity of the calcium ion. The present invention provides a novel calcium receptor active compound of the formula: Ar [CR1R2] pX- [CR3R4] q [CR5R6] -NR7- [CR8R9] -Ar2 (1) wherein: rt_ is selected from the group which consists of aryl, heteroaryl, bis (arylmethyl) amino, bis (heteroarylmethyl) amino and arylmethyl (heteroarylmethyl) amino; X is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl and amino; R1, R2, R3, R4, R5, R6, R8 and R9 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, trihalogenomethyl, aryl, heteroaryl, heteroalicyclic, halogen, hydroxy, alkoxy, thioalkoxy, aryloxy , thioaryloxy, carbonyl, thiocarbonyl, C-carboxyl, O-carboxyl, C-amido, N-amido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, cyano, nitro, amino and NR10R11; wherein: R 10 and R 11 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, carbonyl, trihalogenoacetyl, sulfonyl, trihalogenomethanesulfonyl and, in combination, a five or six membered heteroalicyclic ring containing at least a nitrogen; any two adjacent "R" groups can be combined to form five or six membered fused cycloalkyl groups; R7 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, halogen, cyano, hydroxy, alkoxy, O-carbonyl, trihalogenoacetyl and trihalogenomethanesulfonyl; Ar2 is selected from the group consisting of aryl and heteroaryl; p is an integer from 0 to 6, inclusive; and q is an integer from 0 to 14, inclusive; or a pharmaceutically acceptable salt or a hydrate of said compound. As used herein, the term "aryl" refers to a monocyclic or polycyclic ring-fused group, wholly carbon (i.e., rings that share adjacent pairs of carbon atoms) in which one or more rings have a fully conjugated pi electron system. Examples, without limitation, of the aryl groups are: phenyl, naphthyl, anthracenyl, phenanthrenyl, fluorenyl and indanyl. The aryl group may be substituted or unsubstituted. When substituted, the substituted group or groups are preferably selected from one or more of halogen, trihalogenomethyl, alkyl, alkenyl, alkynyl, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, carbonyl, thiocarbonyl, C- carboxy, O-carboxy, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, sulfinyl, sulfonyl, S-sulfonamido, N-sulfonamido, trihalogenomethanesulfonamido, amino and NR10R11, wherein : R? and R are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, sulfonyl, trihalogenomethanesulfonyl and, combined, a five or six membered heteroalicyclic ring, and said heteroalicyclic ring may be unsubstituted or substituted with one or more halogens. A "heteroaryl" group refers to a monocyclic or fused ring group (i.e., rings that share an adjacent pair of atoms) having in the ring or rings one or more atoms selected from the group consisting of nitrogen, oxygen and sulfur and, in addition, at least one of the rings has a completely conjugated pi electron system. Examples are, without limitation, heteroaryl groups: furan, dibenzofuran, carbazole, acridine, thiophene, imidazole, benzimidazole, oxazole, thiazole, phenothiazine, triazole, thiadiazole, pyrazole, benzoxazole, benzthiazole, indole, benzofuran, indazole, pyridine, pyrimidine, quinoline, isoquinoline, quinazoline, purine, phthalazine and flavone. The heteroaryl group can be substituted or unsubstituted.

When substituted, the group or groups substituted is preferably selected from one or more of: alkyl, cycloalkyl, halogen, trihalogenomethyl, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, carbonyl, thiocarbonyl, sulfonamido, C-carboxy, O-carboxy, sulfinyl, sulfonyl, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, trihalogenometansulfamido, amino and NR 0R ^ -, where R and R are as previously defined here. As used herein, the term "alkyl" refers to a saturated aliphatic hydrocarbon that includes straight chain and branched chain groups. Preferably, the alkyl group has from 1 to 20 carbon atoms. More preferable is an alkyl of average size having from 1 to 10 carbon atoms. Most preferably, it is a lower alkyl having from 1 to 4 carbon atoms. The alkyl group may be substituted or unsubstituted. When substituted, preferably the substituent group or groups is / are one or more individually selected from cycloalkyl, aryl, heteroaryl, heterarolycyclic, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, halogen, carbonyl, thiocarbonyl, O -carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, C-amido, N-amido, C-carboxy, O-carboxy, nitro, sulfonamido, trihalogenomethanesulfonamido, amino and R10R1, wherein R10 and R11 are as defined here previously. More preferably, the alkyl group is a lower or middle alkyl, which is optionally substituted with one or more groups independently selected from halogen, hydroxy, nitro, cyano and unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, and lower alkyl not substituted, and a lower alkyl substituted with one or more halogens. The "cycloalkyl" group refers to a group * totally of monocyclic carbon or of fused ring, that is to say, rings that share an adjacent pair of atoms of carbon, in which none of the rings have a system of ^^ fully conjugated pi electron. Examples, without limitation, of cycloalkyl groups are: cyclopropane, cyclobutane, cyclopentane, cyclopentene, cyclohexane, cyclohexadiene, cycloheptane and cycloheptatriene. A group Cycloalkyl can be substituted or unsubstituted. when substituted, the substituent group or groups are preferably one or more, individually selected from: alkyl, aryl, heteroaryl, heteroalicyclic, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, halogen, Carbonyl, thiocarbonyl, C-carboxyl, 0-carboxyl, 0-carbamyl, N-carbamyl, C-amido, N-amido, S-sulfonamido, N-sulfonamido, nitro, amino and NR10R1: L; wherein: R10 and R11 are as previously defined herein. Preferably the cycloalkyl group is selected from unsubstituted cyclopropane, Unsubstituted cyclopentane, unsubstituted cyclohexane and cyclopropane, cyclopentane and cyclohexane substituted with one or more groups independently selected from halogen, nitro, cyano, hydroxy, unsubstituted lower alkoxy, C-carboxyl, where R "is unsubstituted lower alkyl and O -carboxyl, wherein R "is unsubstituted lower alkyl. An "alkenyl" group refers to an alkyl group, as defined herein, - which consists of two carbon atoms and at least one carbon-to-carbon double bond. A "lower alkenyl" group refers to a lower alkyl group that contains at least one double bond. A "cycloalkenyl" group refers to a cycloalkyl group that contains one or more double bonds in the ring, where the double bonds do not produce a fully conjugated pi electron system within the ring. An "alkynyl" group refers to an alkyl group, as defined herein, consisting of at least two carbon atoms and at least one triple carbon to carbon ligation. A "lower alkynyl" group refers to a lower alkyl group that contains at least one triple ligation. A "heteroalicyclic" group refers to a monocyclic or fused ring group having in the ring or rings one or more atoms selected from the group consisting of nitrogen, oxygen and sulfur. The rings may also have one or more double bonds. However, none of the rings has a fully conjugated pi electron system. The heteroalicyclic ring can be substituted or unsubstituted. When substituted, the group or groups preferably substituted are one or more selected from alkyl, cycloalkyl, halogen, trihalogenomethyl, hydroxy, alkoxy, aryloxy, thiohydroxy, thioalkoxy, thioaryloxy, cyano, nitro, carbonyl, thiocarbonyl, C-carboxy, O-carboxy, 0-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, sulfinyl, sulfonyl, S-sulfonamido, N-sulfonamido, C-amido, N-amido, am no NR 10? R11, • where : R10? and R11 are as previously defined herein. A "phenyl" group refers to an aryl group with a six-membered ring. A "benzyl" group refers to a phenyl-CH2 group- A "hydroxy" group refers to an -OH group. An "alkoxy" group refers to both a 0-alkyl group and an O-cycloalkyl group, as defined herein; preferably an alkoxy group refers to a methoxy or trihalogenomethoxy group. A "trihalogenomethoxy" group refers to a Y3CO- group being Y as defined herein; preferably, Y is fluorine. A "benzyloxy" refers to an O-benzyl group. An "aryloxy" group refers to both an -O-aryl group and an -O-heteroaryl group, as defined herein. A "phenoxy" group refers to an aryloxy group in which the aryl group is a phenyl group. A "thiohydroxy" group refers to a -SH group. A "thioalkoxy" group refers to both a -S-alkyl group and a -S-cycloalkyl group, as defined herein.

A "thioaryloxy" group refers to both a -S-aryl group and a -S-heteroaryl group, as defined herein. A "carbonyl" or "acyl" group refers to a group -C (= 0) -R ", where R" is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, heteroaryl (attached through a ring carbon) and heteroalicyclic (attached through a ring carbon) ), as defined here. A "formyl" group refers to a carbonyl group, where R "is hydrogen An" acetyl "group refers to a carbonyl group, where R" is CH3. An "acetyl" group refers to a group -C (= S) -R ", where R" is as defined herein. A "trihalogenomethyl" group refers to a -CY3 group, wherein Y is a halogen group; preferably Y is fluorine. A "trihalogenoacetyl" group refers to a group Y3CC (= 0) - where Y is as defined herein. A "C-carboxyl" group refers to groups C (= 0) 0 -R ", where R" is as defined herein. An "O-carboxyl" group refers to a group R "C (= 0) 0-, where R" is as defined herein. An "acetoxy" group refers to a 0-carboxyl group, wherein R "is CH3 A" carboxylic acid "group refers to a C-carboxyl group in which R" is hydrogen.

A "halogen" or "halo" group refers to fluorine, chlorine, bromine or iodine. A "trihalogenomethanesulfonyl" group refers to Y3CD (= 0) 2 ~ groups in which Y is as defined above. A "trihalogenomethanesulfonamide" group refers to a Y3CS (= 0) 2 R10- group, where Y and R10 are as defined herein. A "sulfinyl" group refers to a group -S (= 0) -R ", wherein R" is as defined herein or R "may not exist if more bonds S are already in use internally in a particular molecule. A "sulfonyl" group refers to a group -S (= 0) 2R "wherein R" is as defined herein, or R "may not exist if both bonds S are already in use internally in a particular molecule. An "S-sulfonamido" group refers to a group -S (= 0) 2NR10R1, wherein R10 and R11 are as defined herein. An "N-sulfonamido" group refers to a group R 10 S (0) 2 R 1 -, wherein R 10 and R 11 are as defined herein. An "O-carbamyl" group refers to a group -OC (= O) NR10Rl wherein R10 and R11 are as defined herein. A "N-carbamyl" group refers to a group R10OC (= O) NR1-, where R10 and R11 are as defined herein. An "O-thiocarbamyl" group refers to a group -OC (= S) NR10Rl, where R10 and R11 are as defined herein.

A "N-thiocarbamyl" group refers to a group R 0OC (= S) NR 1 -, where R 10 and R 11 are as defined herein. An "amino" group refers to a group -NRx0Rl, where R and R are as defined herein. A "C-amido" group refers to a group -C (= O) NR10R1: L, where R10 and R11 are as defined herein. An "N-amido" group refers to a group -R10C (= O) NR11, where R10 and R11 are as defined herein. A "nitro" group refers to a group -NO2 - A "methylenedioxy" group refers to an -OCH2O- group in which the two oxygens are covalently bonded to the adjacent carbon atoms of an aryl or heteroaryl group. An "ethylenedioxy" group refers to -OCH2CH2O- groups in which the two oxygens are covalently bonded to carbon atoms adjacent to an aryl or heteroaryl group. Preferably, in the formula (1), R is selected from the group consisting of hydrogen, unsubstituted lower alkyl and lower alkyl substituted with one or more halogens; R1, R2, R3, R4, R5, R6 and R7 are hydrogen; and R8 and R9 are independently selected from the group consisting of hydrogen, unsubstituted alkyl, lower alkyl substituted with one or more halogens, unsubstituted alkenyl, lower alkenyl substituted with one or more halogens, unsubstituted alkynyl, alkynyl substituted with one or more halogen and, in combination, unsubstituted cycloalkyl and cycloalkenyl. It is also preferred that Ar? _ Is selected from the group consisting of phenyl, naphthyl, indolyl, fluorenyl, dibenzofuranyl, carbazolyl, benzoxazol-2-yl, benzothiazol-2-yl, pyridin-4-yl, quinolin-2-yl and dibenzylamino, and Ar 2 is selected from the group consisting of phenyl, naphthyl, quinolin-4-yl, pyridin-2-yl, pyridin-3-yl, pyridin-4- ilo, pyrimidinyl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, pyrrol-2-yl and pyrrole-3-yl. It is more preferred that Art_ is phenyl substituted with one or more groups selected from the group consisting of unsubstituted lower alkyl, halogen, trihalogenomethyl, unsubstituted lower alkoxy, trihalogenomethoxy, trihalogenoacetyl and nitro; and that r2 is selected from the group consisting of optionally substituted phenyl and optionally substituted naphthyl. It is further preferred that Ar is 3-methoxyphenyl or unsubstituted naphthyl. Q Q Preferably, R ° is hydrogen, R ^ is methyl and X is oxygen or sulfur. In another aspect, the present invention provides a compound of the formula: Ar3- (CHR12) rQ- (CH2) S-CHR13-NH-CR1 R15-Ar4 (2) wherein: Ar3 is selected from the group consisting of aryl and heteroaryl, optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkenyl, lower alkenyl substituted with one or more halogens, halogen, hydroxy, alkoxy unsubstituted lower, lower alkoxy substituted with one or more halogens, unsubstituted lower thioalkoxy, nitro, formyl, acetoxy, acetyl, -CH2OH, CH3CH (OH) -, -C (= 0) NH2, cyano, -N (lower alkyl 2, phenyl, phenoxy, benzyl, benzyloxy, methylenedioxy, ethylenedioxy, 6,6-dimethylbenzyl and -OCH 2 COOH; Ar 4 is selected from the group consisting of aryl and heteroaryl optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkenyl, lower alkenyl substituted with one or more more halogens, unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, hydroxy, lower thioalkoxy, halogen, methylenedioxy, ethylenedioxy, acetoxy, -OCH2COOH, -C (= 0) NH2, cyano and -CH2OH; r is an integer from 0 to 6, inclusive; s is an integer from 0 to 14, inclusive, -Q is selected from the group consisting of oxygen, sulfur, carbonyl and -NH-; R 3 is hydrogen or lower alkyl; and R14 and R15 are independently selected from the group consisting of hydrogen, alkyl and, in combination, cycloalkyl and cycloalkenyl, or a pharmaceutically acceptable salt or a pharmaceutically acceptable hydrate of said compound.

Preferably, in formula (2), r3 is selected from the groups consisting of unsubstituted phenyl, phenyl substituted with one or more groups selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, halogen, unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, nitro, dimethylamino and unsubstituted phenyl and optionally substituted naphthyl; and R4 is selected from the groups consisting of unsubstituted phenyl, phenyl substituted with one or more groups selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkoxy, substituted lower alkoxy, one or more halogens and halogen, and optionally substituted naphthyl. In another aspect, the present invention provides a compound of the formula: wherein: r5 is aryl, dicyclic or tricyclic heteroaryl, arylmethyl (arylmethyl) amino, heteroarylmethyl (heteroarylmethyl) -amino or arylmethyl (heteroarylmethyl) amino, optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl , unsubstituted lower alkenyl, halogen, hydroxy, unsubstituted lower alkoxy, unsubstituted lower thioalkoxy, lower alkyl substituted with one or more halogens, lower alkenyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, formyl , acetoxy, acetyl, -CH2OH, CH3CH (0H) -, C (= 0) NH2, cyano, N (unsubstituted lower alkyl) 2 phenyl, phenoxy, benzyl, benzyloxy, O, O-dimethylbenzyl, methylenedioxy, ethylenedioxy and - OCH2COOH; Arg is aryl, or dicyclic or tricyclic heteroaryl optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkenyl, lower alkenyl substituted with one or more halogens , unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, halogen, hydroxy, unsubstituted lower trialkoxy, lower trialkoxy substituted with one or more halogens, benzyloxy, methylenedioxy, ethylenedioxy, acetoxy, -COH2COOH, -C (= 0) NH2, cyano and -CH2OH; t is 0 or 1; u is an integer from 0 to 11, inclusive; W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl and amino; R 16 and R 17 are H or unsubstituted lower alkyl; and R 1 R is unsubstituted lower alkyl; or a pharmaceutically acceptable salt or a pharmaceutically acceptable hydrate of said compound.

Preferably, in the formula (3), Ar5 is phenyl, indole, benzothiazole, benzoxazole, dibenzofuran, carbazole, pyridine, fluorene, quinoline, naphthalene, chromenone, tetrahydrobenzothiazepine, dibenzylamino, Benzyl (naphthylmethyl) amino, benzyl (pyridylmethyl) amino, thienylmethyl (benzyl) mino, furylmethyl (benzyl) amino or N-alkyl-pyrrolylmethyl (benzyl) amino optionally substituted with one or more groups independently selected from the group consisting of lower alkyl unsubstituted, halogen, alkoxy Lower unsubstituted, lower alkyl substituted with one or ^ more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino and unsubstituted phenyl; and Arg is thiophene, furan, pyrrole, phenyl, naphthalene, pyridine, pyrazine or thiazole optionally substituted with one or more groups Independently selected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more • halogens, lower alkoxy substituted with one or more halogens, hydroxy and benzyloxy optionally substituted with halogen or methyl. More preferably, Ar5 is selected from the group consisting of phenyl optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens and lower alkoxy substituted with one or more halogens; and Arg is methoxyphenyl or O-naphthyl. It is also preferred that Ar5 is dibenzylamino, benzyl (naphthylmethyl) amino or benzyl (pyridylmethyl) -amino, optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, substituted lower alkyl with one or more halogens and lower alkoxy substituted with one or more halogens; and Arg is naphthyl or methoxyphenyl. It is more preferred that Ar5 is dibenzylamino optionally substituted with unsubstituted alkyl and that Arg is ßf-naphthyl. Preferably, the compound of the present invention represented by the formulas (1), (2) or (3) is the R-enantiomer. The present invention also provides a prodrug of any of the compounds described above. The present invention provides a method for modulating calcium receptor activity using a compound described herein. Incorporated compounds preferably modulate an interaction of Ca2 + with Ca receptors, by reproducing or mimicking (including enhancing) the effect of Ca on a Ca receptor (calcimimetic modulation) or by blocking the effect of Ca + on a Ca2 + receptor (calcilytic modulation); preferably calcimimetic modulation. A method is also provided for treating a patient with disorders characterized by abnormal concentrations of one or more inorganic ions or other physiological biochemical substances, whose concentration is regulated by the activity of one or more calcium receptors. In particular, treatment is contemplated using the compounds described herein for disorders characterized by extracellular Ca ([Ca]) concentration or abnormal intracellular Ca ([Ca +] j_) concentration in one or more cells, including, for example , but without limitation, parathyroid cells, osseous osteoclasts, juxtaglomerular kidney cells, proximal tubule kidney cells, keratinocytes, parafollicular thyroid cells and placental trophoblasts. An "abnormal" state is characterized by a level of a property that is statistically different from the level of that property observed in patients who do not suffer from a particular disorder. Thus, for example, the term "abnormal" when referring to concentrations of inorganic ion, refers to a concentration of the ion in question that would be recognized by the members of a medical community as outside the normal range of said concentration of ions in the healthy patients. As used herein, the terms "treatment", "treating" and "treatment" refer to a method for alleviating, abrogating and / or having a prophylactic effect with respect to a disease and / or disorder and / or a or more of its concomitant symptoms, preferably all of them. In another aspect, the present invention provides a method for treating or preventing primary and secondary hyperparathyroidism, renal osteodystrophy, hypercalcemic malignancy, osteoporosis, Paget's disease and hypertension, which comprises administering a therapeutically effective amount of a compound of this invention to a patient. The term "administer", as used herein, refers to a method for introducing a compound of this invention in vi tro or in vivo. Thus, for example, the importance of the activity of the inorganic ion receptor can be studied and the associated diseases and disorders can be prevented or treated by the compounds and methods that are discussed herein. The cells that exist outside the organism can be maintained or developed in cell culture dishes. In this context, the ability of a particular compound to affect the activity of an inorganic ion receptor can be determined, ie the IC50 or CE5, preferably the EC50 / of a compound, as defined below, before try to use 'the compounds in complex multicellular living organisms, as in a human. For cells outside the organism, there are multiple methods and are well known to those skilled in the art, for administering compounds including, but not limited to, cell microinjection, transformation and numerous carrier techniques. For cells housed within a multicellular living organism, there are also thousands of methods, and likewise are well known to those skilled in the art to administer compounds including, but not limited to, parenteral, dermal, injection and aerosol applications . The present invention incorporates a method for the modulation of one or more activities of an inorganic ion receptor, using the compounds described herein. It is preferred that the inorganic ion receptor be a receptor of Ca. The compounds of this invention can mimic (including enhancing) or blocking the effect of extracellular Ca2 + on a calcium receptor. The preferred use of said compounds is to treat selected disorders by modulating the inorganic ion activity. In particular, the compounds of this invention can be used to treat the indicated disorders by modulating the Ca receptor activity. Extracellular Ca is under homeostatic control and controls various procedures such as blood coagulation, excitability of nerves and muscles and proper bone formation. Calcium receptor proteins allow certain specialized cells to respond to changes in the extracellular Ca concentration. For example, extracellular Ca inhibits the secretion of parathyroid hormone from parathyroid cells, inhibits bone resorption by osteoclasts and stimulates the secretion of calcitonin from C cells. Compounds that modulate inorganic ion receptor activity can be used to treat diseases or disorders, affecting one or more activities of an inorganic ion receptor, which results in a beneficial effect for the patient. For example, osteoporosis in an age-related disorder, characterized by loss of bone mass and increased risk of bone fracture. Compounds that block osteoclastic bone resorption, either directly (for example, an osteoclast ionymimetic compound) or indirectly, by increasing the levels of endogenous calcitonin (for example, a C-cell ionymimetic), and / or decreasing hormone levels Parathyroid glands (eg, a parathyroid cell ionymimetic), can slow bone loss and, thus, result in beneficial effects in patients suffering from osteoporosis. Additionally, it is known that an intermittent low dosage with HPT results in an anabolic effect on bone mass and proper bone remodeling. Thus, compounds and dose regimens that evoke transient increases in parathyroid hormone (e.g., intermittent dosing with a parathyroid cell ionlytic) can increase bone mass in patients suffering from osteoporosis. Additionally, diseases or disorders characterized by a defect in one or more inorganic ion receptor activities can be treated by the present invention. For example, certain forms of primary hyperparathyroidism are characterized by abnormally high levels of parathyroid hormone and decreased thyroid gland responsiveness to circulating calcium. Calcium receptor modulating agents can be used to modulate the responsiveness of parathyroid cells to calcium. It is preferred that the compound modulates the activity of the calcium receptor and is used in the treatment of diseases or disorders that may be affected by the modulation of one or more calcium receptor activities. Preferably the disease or disorder is characterized by abnormal homeostasis of bone and minerals, more preferably, by calcium homeostasis. Abnormal calcium homeostasis is characterized by one or more of the following activities: (1) an abnormal increase or decrease in serum calcium; (2) an abnormal increase or decrease in urinary calcium excretion; (3) an abnormal increase or decrease in calcium levels in the bone, for example, as determined by bone mineral density measurements; (4) an abnormal absorption of dietary calcium; and (5) an abnormal increase or decrease in the increase or decrease of circulating messengers or circulating hormones that affect calcium homeostasis, such as parathyroid hormone and calcitonin. The abnormal increase or decrease in those different aspects of calcium homeostasis is related to that which occurs in the general population and is generally associated with a disease or disorder. More generally, a molecule that modulates the activity of an inorganic ion receptor is useful in the treatment of diseases characterized by abnormal homeostasis of inorganic ion. Preferably the molecule modulates one or more inorganic ion receptor effects. The modulatory atents of the inorganic ion receptor include the ionimetics, the ionlíticos, calcimiméticos and calcilíticos. Ionimetics are molecules that reproduce or mimic the effects of increasing the concentration of ions in an inorganic ion receptor. Preferably the molecule affects one or more calcium receptor activities. Calcimimetics are ionimetics that affect one or more of the calcium receptor activities and, preferably, bind to a calcium receptor. Ionitics are molecules that reduce or block one or more activities caused by an inorganic ion or an inorganic ion receptor. Preferably, the molecule inhibits one or more calcium receptor activities. Calcilytics are ionlytics that inhibit one or more calcium receptor activities evoked by extracellular calcium and, preferably, bind to a calcium receptor. The inorganic ion receptor modulating agents can be formulated as pharmacological agents or compositions to facilitate administration to a patient.

Pharmacological agents or compositions are agents or compositions having a suitable form for administration to a mammal, preferably a human. In the art, considerations to forms suitable for administration are known, and include toxic effects such as solubility, route of administration and maintenance of activity. Other aspects of the present invention incorporate methods for using agents described herein to treat diseases or disorders, modulating the activity of the inorganic ion. Patients who need such treatments can be identified by common medical techniques, for example, by routine blood tests. For example, by detecting a deficiency in the protein whose production or secretion is affected by changes in inorganic ion concentrations, or by detecting abnormal levels of inorganic ions or hormones that effect the homeostasis of the inorganic ion. Therapeutic methods involve administering to the patient a therapeutically effective amount of an inorganic ion receptor modulating agent. In preferred embodiments, those methods are used to treat a disease or disorder, characterized by abnormal homeostasis of inorganic ion, more preferable, a disease or disorder characterized by abnormal calcium homeostasis. Diseases and disorders characterized by abnormal calcium homeostasis include: hyperparathyroidism, osteoporosis, renal osteodystrophy and other bone and mineral-related disorders and the like (as described, for example, in common medical texts and quotients, such as in "Harrison's Principles of Infernal Medicine "). Said diseases and said disorders are treated using calcium receptor regulating agents that reproduce or mimic or block one or more of the effects of Ca and, in that way, directly or indirectly affect the levels of proteins or other molecules in the body. of the patient. By "therapeutically effective amount" is meant an amount of an agent that alleviates to some extent one or more symptoms of the disease or disorder in the patient, or that returns to normal either partially or completely, one or more of the physiological or biochemical parameters associated with, or causing the disease or disorder. In a preferred embodiment, the patient has a disease or disorder characterized by an abnormal level of one or more components regulated by the calcium receptor and the molecule is active in a calcium receptor of a cell selected from the group consisting of parathyroid cell , bone osteoclast, juxtaglomerular kidney cell, proximal tubular kidney cell, distal tubular kidney cell, central nervous system cell, peripheral nervous system cell, thick ascending branch cell of Henle's loop and / or the collecting duct, keratinocytes of the epidermis, parafollicular cells of the thyroid (C cells), intestinal cells, trophoblasts of the placenta, platelets, vascular smooth muscle cells, cardiac atrial cells, gastrin-secreting cells, glucagon-secreting cells, mesangial kidney cells, cells mammary, beta cells, fat / fat cells, immune cells and cells of the tract gastrointestinal It is more preferred that the cell be a parathyroid cell and the molecule reduces the level of parathyroid hormone in the patient's serum. It is even more preferred that the level be reduced to a sufficient extent to cause a decrease in the Ca2 + of the plasma. Very preferable, the level of parathyroid hormone is reduced to that which is present in a normal individual. Thus, the present invention incorporates agents and methods useful in the treatment of diseases and disorders, modulating the activity of the inorganic ion receptor. For example, the molecules of the present invention can be used to target calcium receptors in the different cell types that detect and respond to changes in external calcium. For example, molecules that mimic or reproduce external calcium can be used to selectively depress parathyroid hormone secretion from parathyroid cells, or depress bone resorption by osteoclasts, or stimulate the secretion of calcitonin from the C cell. Such molecules can be used to treat diseases or disorders characterized by abnormal calcium homeostasis, such as hyperparathyroidism, renal osteodystrophy and osteoporosis. Other aspects and advantages of the invention will be apparent from the following description of its preferred embodiments, and from the claims.

BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows the structures of the compounds of the present invention synthesized in examples 1 to 23. Figure 2 shows the scheme of the synthesis of the compound of the present invention of the formula (1), wherein X is O. Figure 3 shows the scheme of the synthesis of the compound of the present invention of the formula (1), wherein X is S. Figure 4 shows the scheme of the synthesis of the compound of the present invention of the formula (1) , wherein Ar- is benzothiazole or benzoxazole. Figure 5 shows the structures of the compounds of the present invention synthesized in examples 24 to 26, and the scheme of their synthesis. Figure 6 shows the structures of the compounds of the present invention synthesized in examples 27 to 32, and the scheme of their synthesis.

Figure 7 shows the structures of the compounds of the present invention synthesized in examples 33 to 36, and the scheme of their synthesis. Figure 8 shows the structures of the compounds of the present invention synthesized in examples 37 to 40, and the scheme of their synthesis. Figure 9 shows the structures of the compounds of the present invention synthesized in examples 41 and 42, and the scheme of their synthesis. Figure 10 shows the structures of the compounds of the present invention synthesized in examples 43 to 56. Figure 11 shows the structures of the compounds of the present invention synthesized in examples 57 to 70. Figure 12 shows the structures of the Compounds of the present invention synthesized in examples 71 to 84. Figure 13 shows the structures of the compounds of the present invention synthesized in examples 85 and 86. Figure 14 shows the structure of the compound of the present invention, synthesized in the example 88, and the outline of its synthesis. Figure 15 shows the structures of the compounds of the present invention synthesized in Examples 89 and 90. Figure 16 shows the structure of the compound of the present invention, synthesized in Examples 91 to 93, and the scheme of its synthesis. Figure 17 shows the structures of the compounds of the present invention, synthesized in Examples 94 to 96, and the scheme of their synthesis. Figure 18 shows the structures of the compounds of the present invention, synthesized in Examples 97 to 100, and the scheme of their synthesis. Figure 19 shows the structures of the compounds of the present invention, synthesized in examples 101 to 103, and the scheme of their synthesis. Figure 20 shows the structures of the compounds of the present invention, synthesized in Examples 104 to 106, and the scheme of their synthesis. Figure 21 shows the structures of the compounds of the present invention, synthesized in examples 107 to 109, and the scheme of their synthesis. Figure 22 shows the structures of the compounds of the present invention, synthesized in examples 110 to 112 and the scheme of their synthesis. Figure 23 shows the structures of the compounds of the present invention, synthesized in examples 113 to 115, and the scheme of their synthesis. Figure 24 shows the structures of the compounds of the present invention, synthesized in Examples 116 to 118, and the scheme of their synthesis. Figure 25 shows the structures of the compounds of the present invention, synthesized in examples 119 to 121, and the scheme of their synthesis. Figure 26 shows the structures of the compounds of the present invention, synthesized in Examples 122 to 134, and the scheme of their synthesis. Figure 27 shows the structures of the compounds of the present invention, synthesized in examples 135 to 147, and the scheme of their synthesis. Figure 28 shows the structures of the compounds of the present invention, synthesized in Examples 148 to 189, and the scheme of their synthesis. Figure 29 shows the structures of the compounds of the present invention, synthesized in examples 190 to 231, and the outline of its synthesis. Figure 30 shows the structures of the compounds of the present invention, synthesized in examples 232 to 271, and the scheme of their synthesis. Figure 31 shows the structures of the compounds of the present invention, synthesized in examples 272 to 313, and the scheme of their synthesis. Figure 32 shows the structures of the compounds of the present invention, synthesized in examples 314 to 355, and the scheme of their synthesis.

Figure 33 shows the structures of the compounds of the present invention, synthesized in examples 356 to 387, and the scheme of their synthesis. Figure 34 shows the structures of the compounds of the present invention, synthesized in examples 388 to 407, and the scheme of their synthesis. Figure 35 shows the structures of the compounds of the present invention, synthesized in examples 408 to 413, and the scheme of their synthesis. Figure 36 shows the structures of the compounds of the present invention, synthesized in examples 416 to 428, and the scheme of their synthesis. Figure 37 shows the structures of the compounds of the present invention, synthesized in examples 429 to 441, and the scheme of their synthesis. Figure 38 shows the structures of the compounds of the present invention, synthesized in Examples 442 to 455, and the scheme of their synthesis. Figure 39 shows the structures of the compounds of the present invention, synthesized in Examples 456 to 469, and the scheme of their synthesis. Figure 40 shows the structures of the compounds of the present invention, synthesized in examples 470 to 480, and the scheme of their synthesis. Figure 41 shows the structures of the compounds of the present invention, synthesized in examples 481 to 490, and the scheme of their synthesis. Figure 42 shows the structures of the compounds of the present invention, synthesized in Examples 491 to 495, and the scheme of their synthesis. Figure 43 shows the structures of the compounds of the present invention, synthesized in examples 496 to 504, and the scheme of their synthesis. Figure 44 shows the structures of the compounds of the present invention, synthesized in examples 505 to 517, and the scheme of their synthesis. Figure 45 shows the structures of the compounds of the present invention, synthesized in examples 518 to 529, and the scheme of their synthesis. Figure 46 shows the changes in the level of Ca in the plasma of the rats to which compound K-2027 of the present invention was administered. Figure 47 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2052 of the present invention was administered. Figure 48 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2076 of the present invention was administered. Figure 49 shows the changes in the level of Ca in the plasma of the rats to which compound K-2087 of the present invention was administered. Figure 50 shows the changes in the level of Ca in the plasma of the rats to which compound K-2117 of the present invention was administered. Figure 51 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2240 of the present invention was administered. Figure 52 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2243 of the present invention was administered. Figure 53 shows the changes in the level of Ca in the plasma of the rats to which compound K-2246 of the present invention was administered. Figure 54 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2247 of the present invention was administered. Figure 55 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2250 of the present invention was administered. Figure 56 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2257 of the present invention was administered. Figure 57 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2259 of the present invention was administered. Figure 58 shows the changes in the level of Ca + in the plasma of the rats to which compound K-2262 of the present invention was administered.

Figure 59 shows the changes in the level of Ca in the plasma of the rats to which it was administered the compound K-2263 of the present invention. Figure 60 shows the changes in the level of Ca in the plasma of the rats to which compound K-2264 of the present invention was administered. Figure 61 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2265 of the present invention was administered. Figure 62 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2266 of the present invention was administered. Figure 63 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2267 of the present invention was administered. Figure 64 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2269 of the present invention was administered. Figure 65 shows the changes in the level of Ca in the plasma of the rats to which compound K-2270 of the present invention was administered. Figure 66 shows the changes in the level of Ca in the plasma of the rats to which compound K-2271 of the present invention was administered. Figure 67 shows the changes in the level of Ca in the plasma of the rats to which compound K-2272 of the present invention was administered. Figure 68 shows the changes in the level of Ca in the plasma of the rats to which compound K-2279 of the present invention was administered. Figure 69 shows the changes in the level of Ca in the plasma of the rats to which compound K-2280 was administered. the present invention. Figure 70 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2281 of the present invention was administered. Figure 71 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2282 of the present invention was administered. Figure 72 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2283 of the present invention was administered. Figure 73 shows the changes in the level of Ca in the plasma of the rats to which compound K-2284 of the present invention was administered. Figure 74 shows the changes in the level of Ca in the plasma of the rats to which compound K-2286 of the present invention was administered. Figure 75 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2287 of the present invention was administered. Figure 76 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2288 of the present invention was administered. Figure 77 shows the changes in the level of Ca in the plasma of the rats to which compound K-2289 of the present invention was administered. Figure 78 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2290 of the present invention was administered. Figure 79 shows the changes in the level of Ca in the plasma of the rats to which compound K-2291 of the present invention was administered. Figure 80 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2292 of the present invention was administered. • Figure 81 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2293 of the present invention was administered. Figure 82 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2294 of the present invention was administered. Figure 83 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2296 of the present invention was administered. Figure 84 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2297 of the present invention was administered.

Figure 85 shows the changes in the level of Ca in the plasma of the rats to which compound K-2298 of the present invention was administered. Figure 86 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2299 of the present invention was administered. Figure 87 shows the changes in the level of Ca in the plasma of the rats to which compound K-2300 of the present invention was administered. Figure 88 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2301 of the present invention was administered. Figure 89 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2302 of the present invention was administered. Figure 90 shows the changes in the level of Ca + in the plasma of the rats to which compound K-2303 of the present invention was administered. Figure 91 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2304 of the present invention was administered. Figure 92 shows the changes in the level of Ca2 + in the plasma of the rats to which the compound was administered K-2305 of the present invention. Figure 93 shows the changes in the level of Ca2 + in the plasma of the rats to which compound K-2309 of the present invention was administered. Figure 94 shows the changes in the level of Ca in the plasma of the rats to which compound K-2310 of the present invention was administered. Figure 95 shows the changes in the level of HRT in the plasma of the rats to which the compound K-2076, K-2117 or K-2259 of the present invention was administered. Figure 96 shows relative changes in the level of HPT in the serum of rats given compound K-2076, K-2117 or K-2259 of the present invention, at the level of pre-administration.

THE PREFERRED MODALITIES OF THE INVENTION The present invention describes inorganic ion receptor modulating agents, capable of reproducing or mimicking, or of blocking an effect of an inorganic ion in an inorganic ion receptor. The preferred use of inorganic ion modulating agents is to treat a disease or disorder by modulating the inorganic ion receptor activity. Preferably the molecules are used to treat diseases or disorders characterized by abnormal ion homeostasis, more preferable, abnormal calcium homeostasis. Other uses of the inorganic ion receptor modulating agents, such as diagnostic uses, are known in the art. Nemeth and co-inventors, PCT / US93 / 01642, international publication number WO 94/18959.

I.- THE RECEIVERS OF CALCIUM Calcium receptors and calcium receptors encoding nucleic acid are described by Nemeth and co-inventors, PCT / US93 / 01642, International Publication Number WO 94/18959. Calcium receptors are present in different types of cells, such as parathyroid cells, bone osteoclasts, cells from juxtagíomerular kidney cells, proximal tubule kidney cells, distal tubular kidney cells, cells of the system central nervous system, the cells of the peripheral nervous system, the cells of the thick ascending branch of the Henle's loop and / or the collecting duct, the keratinocytes of the epidermis, the parafollicular cells of the thyroid (C cells), the intestinal cells, the trophoblasts of the placenta, platelets, vascular smooth muscle cells, cardiac atrial cells, gastrin-secreting cells, glucagon-secreting cells, mesangial kidney cells, mammary cells, beta cells, fat / fat cells , the immune cells and the cells of the gastrointestinal tract. The calcium receptor in these cell types may be different. It is also possible for a cell to have more than one type of calcium receptor. The comparison of calcium receptor activities and the amino acid sequences of different cells indicate that there are different types of calcium receptor. For example, calcium receptors can respond to a variety of di and trivalent cations. The parathyroid calcium receptor responds to calcium and Gd3 +, whereas the osteoclasts respond to divalent cations, such as calcium, but do not respond to Gd. Thus, the parathyroid calcium receptor is pharmacologically different from the calcium receptor in the osteoclast. On the other hand, the nucleic acid sequences encoding the calcium receptors herein in the parathyroid cells and in the C cells indicate that those receptors have a very similar amino acid structure. However, calcimimetic compounds exhibit different pharmacology and regulate different activities in parathyroid cells and C cells. Thus, the pharmacological properties of calcium receptors can vary significantly depending on the type of cell or organ in which they are expressed. when calcium receptors may have similar structures. Calcium receptors, in general, have little affinity for extracellular Ca (an apparent Kβ generally greater than about 0.5 mmol). Calcium receptors may include a free or bound effector mechanism, as defined by Cooper, Bloom and Roth, "The Biochemical Basis of Neuropharmacology", chapter 4, and thus, are distinct from extracellular calcium receptors, by example, calmodulin and troponins. Calcium receptors respond to changes in extracellular calcium levels. Exact changes depend on the particular receptor and the cell line that contains the receptor. For example, the in vitro effect of calcium on the calcium receptor in a parathyroid cell includes the following: 1. An increase in internal calcium. This increase is due to the influx of external calcium intake and / or the mobilization of internal calcium. The characteristics of the increase in internal calcium include the following: (a) a rapid (time to peak less than 5 seconds) and transient increase of [Ca] ±, which is refractory to inhibition by 1 mmol of La + or 1 mmol of Gd, and is abolished by the previous treatment with ionomycin (in the absence of extracellular Ca2 +); (b) the increase is not inhibited by dihydropyridines; (c) the transient increase is abolished by pretreatment for 10 minutes with 10 mmol of sodium fluoride; (d) the transient increase is decreased by pretreatment with a protein kinase C (PKC) activator, such as phorbol myristate acetate (PMA), mezerein or (-) - indolactam V. The overall effect of the activator of the protein kinase C is to deviate the concentration-response curve to calcium to the right, without affecting the maximum response; and (e) treatment with pertussis toxin (100 ng / ml for more than 4 hours) does not affect the increase. 2. A rapid increase (less than 30 seconds) in the formation of 1, 4, 5-inositol triphosphate or diacylglycerol. Treatment with pertussis toxin (100 ng / ml for more than 4 hours) does not affect this increase. 3. Inhibition of cyclic AMP formation, stimulated by dopamine and by isoproterenol. This effect is blocked by previous treatment with the pertussis toxin (100 ng / ml for more than 4 hours); and 4. Inhibition of HPT secretion. Treatment with pertussis toxin (100 ng / ml for more than 4 hours) does not affect the inhibition of PTH secretion. Using techniques known in the art, one can easily determine the effect of calcium and other calcium receptors on different cells. These effects may be similar with respect to the increase in internal calcium observed in parathyroid cells. However, the effect is expected to differ in other aspects, such as the provocation or inhibition of a hormone different from parathyroid hormone.

II. - THE MODULATING AGENTS OF THE ION INORGANIC RECEIVER The inorganic ion receptor modulating agents evoke one or more activities of the inorganic ion receptor, or block one or more inorganic ion receptor activities, caused by an extracellular inorganic ion. Calcium receptor modulating agents can mimic or block an effect of extracellular Ca on the calcium receptor. The preferred calcium receptor modulating agents are calcimimetics and calcilytics. The inorganic ion receptor modulating agents can be identified by discriminating molecules that are modeled following a molecule that has been shown to have a particular activity (ie, a leader molecule). Nemeth and co-inventors, PCT / US93 / 01642, international publication number WO 94/18959. The preferred inorganic ion receptor modulating agents described in the present invention have considerably low EC50 values. The EC50 is the concentration of the molecule that evokes a semi-maximal effect. The IC50 is the molecule concentration that evokes a semi-maximal blocking effect. The EC50 or IC50 can be determined by analyzing one or more activities of the inorganic ion in an inorganic ion receptor. Preferably those analyzes are specific for a particular calcium receptor. For example, analyzes that emit hormones whose production or secretion is modulated by a particular inorganic ion receptor are preferred. Increases in [Ca] ± can be detected using normal techniques, such as by using fluorimetric indicators or measuring an increase in Cl ~ current in a Xenopus oocyte injected with nucleic acid encoding a calcium receptor. Nemeth and co-inventors, PCT / US93 / 01642, international publication number WO 94/18959. For example, poly (A) + mRNA can be obtained from cells expressing a calcium receptor, such as a parathyroid cell, bone osteoclast, juxtaglomerular kidney cell, proximal tubule kidney cells, tubular kidney cell. distal, thick ascending branch cell of Henle's curl and / or collecting duct, keratinocyte of the epidermis, parafollicular thyroid cell (C cell), intestinal cell, central nervous system cell, peripheral nervous system cell, trophoblast of the placenta, platelet, vascular smooth muscle cell, cardiac atrial cell, gastrin secreting cell, glucagon secretory cell, mesangial kidney cell, mammary cell, beta cell, fat / adipose cell, immune cell and gastrointestinal tract cell. Preferably the nucleic acid is from a paratoid, C cell or osteoclast cell. It is more preferred that the nucleic acid encode a calcium receptor and be present in a plasmid or vector. Preferably the molecule is a calcimimetic or a calcilytic having an EC50 or IC50 at a calcium receptor of less than or equal to 5 mmoles, and even more preferably less than or equal to 1 mmole, 100 nanomolar, 10 nanomolar or 1 nanomolar . Said lower EC50 or IC50 are advantageous given that they allow lower concentrations of molecules to be used in vivo or in vitro to be diagnostic. The discovery of molecules with such low EC50 or IC50 allows the design and synthesis of additional molecules that have similar potency and effectiveness. In preferred embodiments, the calcium receptor modulating agent is a calcimimetic that inhibits the secretion of parathyroid hormone from an in vitro parathyroid cell and decreases the secretion of HPT in vivo; stimulates the secretion of calcitonin from a C cell in vitro and elevates calcitonin levels in vivo; or blocks osteoclastic bone resorption in vitro and inhibits bone resorption in vivo. In another preferred embodiment, the calcium receptor modulating people is a calcilytic and evokes the secretion of parathyroid hormone from the parathyroid cells in vitro and raises the level of the parathyroid hormone in vivo. Preferably the agent is selectively directed to the inorganic ion receptor activity, more preferably the activity of the calcium receptor in a particular cell. By "selectively" it is meant that the molecule exerts a greater effect by the activity of the inorganic ion receptor on one type of cells than on another type of cells, for a given concentration of agent. Preferably, the differential effect is 10 times or more. Preferably the concentration refers to the concentration in the blood plasma and the effect measured is the production of extracellular messengers, such as plasma calcitonin, parathyroid hormone or plasma calcium. For example, in a preferred embodiment, the agent selectively targets the secretion of HPT with respect to the secretion of calcitonin. In another preferred embodiment, the molecule has an EC50 or IC50 less than or equal to 1 mmol, in one or more, but not in all cells, selected from the group consisting of parathyroid cells, bone osteoclasts, juxtaglomerular kidney cells, cells of proximal tubule kidney, tubular kidney cells, distal, thick ascending branch cells of Henle's curl and / or collecting duct, cells of the central nervous system, cells of the peripheral nervous system, keratinocytes of the epidermis, parafollicular cells of the thyroid (C cells), intestinal cells, trophoblasts of the placenta, platelet, vascular smooth muscle cells, cardiac atrial cells, gastrin-secreting cells, glucagon-secreting cells, mesangial kidney cells, mammary cells, beta cells, fat / fat cells , immune cells and cells of the gastrointestinal tract. Preferably the inorganic ion receptor modulating agents mimic or block all effects of the extracellular ion in a cell having an inorganic ion receptor. For example, calcium receptor modulating agents preferably mimic or block all effects of the extracellular ion in a cell having a calcium receptor. It is not necessary that calcimimetics possess all the biological activities of extracellular Ca; rather, at least one of these activities is imitated. Similarly, calcilytics do not need to reduce or prevent all activities caused by extracellular calcium. Additionally, the different calcimimetics and the different calcilytics do not need to be bound to the same site as the calcium receptor as the extracellular Ca2 +, to exert their effects.

A.- THE CALCIMIMET COS The ability of molecules to mimic or block Ca activity in calcium receptors can be determined using methods known in the art and described by Nemeth and co-inventors PCT / US93 / 01642, International Publication Number WO 94/18959. For example, calcimimetics possess one or more, and preferably all of the following activities, when tested in parathyroid cells in vitro. 1.- The molecule causes a rapid increase (time to the peak less than 5 seconds) and transient in [Ca] j_ that is refractory to inhibition by 1 mmol of La or 1 mmol of Gd3 +. The increase in [Ca2 +] j_ persists in the absence of Ca2 +, but is abolished with ionomycin treatment (in the absence of extracellular Ca2 +); 2. - the molecule potentiates the increases in [Ca2 +] ± unleashed by submaximal concentrations of extracellular Ca2 +; 3. - the increase in [Ca] --_ unleashed by extracellular Ca is not inhibited by dihydropyridines; 4.- the transient increase in [Ca2 +] j_ caused by the molecule is abolished by pretreatment for 10 minutes with 10 mmol of sodium fluoride; 5.- The transient increase in [Ca2 +] - ¡_ caused by the molecule is diminished by the previous treatment with a protein kinase C (PKC) activator, such as phorbol myristate acetate (PMA), mezerein or ( -) -indolactam V. The overall effect of the activator of protein kinase C is to divert the concentration-response curve of the molecule to the right, without affecting the maximum response; 6.- The molecule causes a rapid increase (less than 30 seconds) in the formation of 1, 4, 5-triphosphate of inositol and / or diacylglycerol. 7.- The molecule inhibits the formation of cyclic AMP, stimulated by dopamine or isoproterenol; 8.- the molecule inhibits the secretion of HPT; 9.- pretreatment with pertussis toxin (100 ng / ml for more than 4 hours) blocks the inhibitory effect of the molecule on the formation of cyclic AMP, but does not increase [Ca2 +] j_, 1, 4, 5 - inositol triphosphate nor diacylglycerol, nor decreases the secretion of HPT; 10.- The molecule unleashes increases in the Cl current "in Xenopus oocytes injected with mRNA enriched with poly (A) +, from bovine or human parathyroid cells, but without effect on Xenopus oocytes injected with water, or mRNA. of rat brain or liver, and 11.- Similarly, using a cloned calcium receptor from a parathyroid cell, the molecule will unleash a response in Xenopus oocytes injected with specific cDNA or mRNA, which encode the receptor. activities other than calcium using available techniques Nemeth and co-inventors PCT / US93 / 01642, international publication number WO 94/18959 Parallel definitions of molecules that mimic the activity of Ca or another cell responsive to calcium are apparent in a calcium receptor, from the examples provided herein and from Nemeth and co-inventors PCT / US93 / 01642, international publication number WO 94/18959. The agent, when measured by bioassay such as those described herein or by Nemeth and co-inventors PCT / US93 / 01642, International Publication Number WO 94/18959, has one or more, most preferably all of the following activities: evokes a transient increase in internal calcium, which lasts less than 30 seconds (mobilizing internal calcium); evokes a rapid increase in [Ca] ±, which occurs within 30 seconds; evokes a sustained increase (for more than 30 seconds) in [Ca] j_ (causing an influx of external calcium intake); evokes an increase in the levels of inositol 1,4,5-triphosphate or diacylglycerol, preferably within less than 60 seconds; and inhibits the formation of cyclic AMP, stimulated by dopamine or by isoproterenol. The transient increase in [Ca] j_ is preferably abolished by pre-treatment of the cells for 10 minutes with 10 mmol of sodium fluoride, or the transient increase is decreased by a brief pretreatment (not more than ten minutes) of the cell with a protein kinase C activator, preferably, phorbol myristate acetate (PMA), mezerein or (-) -indolactam V.

B.- THE CALCILITICS The ability of a molecule to block the activity of external calcium can be determined using ordinary techniques. Nemeth and co-inventors PCT / US93 / 01642, international publication number WO 94/18959. For example, molecules that block the effect of external calcium when used in reference to a parathyroid cell possess one or more, and preferably all of the following characteristics, when tested in parathyroid cells in vitro: 1.- the molecule blocks, either partially or completely, the ability of increased concentrations of "extracellular Ca2 +, to: (a) increase [Ca] ¿; (b) mobilize intracellular Ca2 +; (c) increase the formation of 1, 4, 5-inositol triphosphate; (d) decreasing the formation of cyclic AMP, stimulated by dopamine or isoproterenol; and (e) inhibiting the secretion of HPT; 2.- The molecule blocks the increase in Cl current "in Xenopus oocytes injected with poly (A) + mRNA, from bovine or human parathyroid cells, unleashed by extracellular Ca or calcimimetic compounds, but not in oocytes of Xenopus injected with water or without liver mRNA 3.- Similarly, using a cloned calcium receptor from a paratocidal cell, the molecule will block a response in the Xenopus oocytes injected with the specific cDNA, mRNA or cRNA that the receptor encodes of calcium, unbound by extracellular Ca2 + or by a calcimimetic compound.Parallel definitions of molecules that block Ca2 + activity in a cell that responds to calcium, preferably in a calcium receptor, are evident from the examples provided here and in Nemeth and co-inventors PCT / US93 / 01642, international publication number WO 94/18959.

III. - THE TREATMENT OF DISEASES OR DISORDERS A preferred use of the compounds described by the present invention is the treatment or prevention of 5 different diseases or disorders, modulating the activity of the inorganic ion receptor. The inorganic ion receptor modulating agents of the present invention can exert an effect on an inorganic ion receptor, which causes one or more cellular effects that ultimately produce a therapeutic effect. Different diseases and disorders can be treated by means of the present invention, targeting cells having an inorganic ion receptor, such as a calcium receptor. For example, primary hyperparathyroidism (HPT) is characterized by hypercalcemia at high levels of circulating HPT. A defect associated with the main type of HPT is a decreased sensitivity of parathyroid cells to m? the regulation of negative feedback by extracellular Ca2 +.

Thus, in the tissue of patients with primary HPT, the "point fixed extracellular Ca deviated to the right so that higher-than-normal levels of extracellular Ca2 + are required to depress HPT secretion.In addition, in primary HPT, even high concentrations of Ca 24- extracellular frequently depresses the secretions of HPT only partially. In secondary HPT (uremic), a similar increase in the fixed point for extracellular Ca + is observed, although the degree to which Ca + suppresses the secretion of PTH is normal. The changes in the secretion of HPT are parallel to the changes in [Ca] ±; the fixed point for increases in [Ca] induced by extracellular Ca is diverted to the right and the magnitude of such increases is reduced. Molecules that most mimic the action of extracellular Ca are beneficial in the long-term management of both primary and secondary HPT. These molecules provide the additional impetus required to suppress the secretion of PTH, which can not be achieved with the hypercalcemic condition alone, and the therapy helps relieve the hypercalcemic condition. Molecules with greater efficacy than extracellular Ca can resolve the apparent non-suppressible component of HPT secretion, which is particularly difficult in adenomatous tissue. Alternatively or additionally, said molecules can depress the synthesis of PTH, since it has been demonstrated that prolonged hypercalcemia decreases preproHPT mRNA levels in bovine and human adenomatous parathyroid tissue. Prolonged hypercalcemia also depresses the proliferation of parathyroid cells in vitro, so calcimimetics may also be effective in limiting parathyroid cell hyperplasia, characteristics of secondary HPT. Cells other than parathyroid cells may respond directly to physiological changes in extracellular Ca2 + concentration. For example, the secretion of calcitonin from parafollicular cells in the thyroid (C cells) is regulated by changes in the concentration of extracellular Ca. Isolated osteoplasts respond to increases in extracellular Ca2 + concentration, with corresponding increases in [Ca] j that arise partially from the mobilization of intracellular Ca. Increases in [Ca] j_ in osteoclasts are associated with the inhibition of bone resorption. The release of alkaline phosphatase from bone-forming osteoblasts is stimulated directly by calcium. Renin secretion from juxtaglomerular cells in the kidney, such as PTH secretion, is depressed by increased levels of extracellular Ca2 +. Ca causes the mobilization of intracellular Ca2 + in these cells. Other kidney cells respond to calcium in the following manner: high Ca + inhibits the formation of 1.25 (OH) 2-vitamin D by nearby tubular cells, stimulates the production of protein that binds calcium in distal tubular cells and inhibits The tubular reabsorption of Ca + and Mg2 + and the action of vasopressin on the medullarly thick ascending branch of Henle's curl (MTAL), reduces the action of vasopressin in cortical collecting duct cells and affects vascular smooth muscle cells in the blood vessels of the renal glomerulus. Calcium also promotes the differentiation of intestinal goblet cells, mammary cells and skin cells; inhibits the secretion of atrial natriuretic peptide from the cardiac atria; reduces the accumulation of cAMP in platelets; alters the secretion of gastrin and glucagon; it acts on vascular smooth muscle cells to modify the secretion of vasoactive factors in cells, and affects the cells of the central nervous system and the peripheral nervous system. Thus, there are sufficient indications that Ca, in addition to its ubiquitous role as an intracellular signal, also functions as an extracellular signal to regulate the responses of certain specialized cells. The molecules of this invention can also be used in the treatment of diseases or disorders associated with interrupted responses to Ca in those cells. Diseases and disorders that could be treated or prevented, based on affected cells, also increase those of the central nervous system such as attacks, trauma to the head, damage to the spinal cord, damage to nerve cells induced by hypoxia such as cardiac arrest or in neonatal difficulties, epilepsy, neurodegenerative diseases such as Alzheimer's disease, Huntington's disease and Parkinson's disease, dementia, muscle tension, depression, anxiety, panic disorders, obsessive-compulsive disorders, post-traumatic stress disorders , schizophrenia, malignant neuroleptic syndrome and Tourette syndrome; diseases that involve excessive water reabsorption by the kidney, such as inappropriate HAD secretion syndrome (SIAH); cirrhosis, heart failure and nephrosis; hypertension, prevention and / or reduction of renal toxicity from cationic antibiotics (for example, aminoglycoside antibiotics); alterations in intestinal motility such as diarrhea and spastic colon; Gastrointestinal ulcer diseases, gastrointestinal absorption diseases, such as sarcoidosis; and autoimmune diseases and rejections of organ transplants. t While the inorganic ion modulating agents of the present invention will typically be used for human patients, they can also be used to treat identical diseases or disorders in other species of warm-blooded animals, such as other primates, farm animals such as pigs, cattle and birds; and sports animals and pets, such as horses, dogs and cats.

IV.- THE ADMINISTRATION A compound of the present invention or its pharmaceutically acceptable salt, hydrate or prodrug can be administered to a human patient per se or in pharmaceutical compositions, where it is mixed with carriers or one or more suitable excipients. Techniques for the formulation and administration of drugs can be found in "Remington's Pharmaceutical Sciences", Mack Publishing Col, Easton, PA, USA, latest edition. The administration of ionimetics and ionlites is discussed by Nemeth and co-inventors, PCT / US93 / 01642, International Publication Number WO 94/18959. A "pharmaceutical composition" refers to a mixture of one or more of the compounds described herein, or their pharmaceutically acceptable salts, hydrates or prodrugs thereof, with other chemical components such as physiologically acceptable carriers and excipients. The purpose of a pharmacological composition is to facilitate the administration of a compound to an organism. A "prodrug" refers to an agent that is converted to the original drug in vivo. Prodrugs are often useful because, in some situations, they may be easier to administer than the original drug. For example, they may be bioavailable by oral administration while the original drug is not. The prodrug may also have improved solubility in pharmacological compositions, with respect to the original drug. An example, without limitation, of a prodrug, would be a compound of the present invention in which it is administered with an ester (the "prodrug") to facilitate transmission through a cell membrane, when water solubility is not beneficial. , but then metabolically hydrolyzed to the carboxylic acid once it is inside the cell, when the solubility in water is beneficial. As used herein an "ester" is a carboxyl group, as defined herein, wherein R "is any of the aforementioned groups, other than hydrogen.As used herein, a" physiologically acceptable carrier "refers to a carrier or diluent that does not cause significant irritation in an organism and that does not abrogate the biological activity or the properties of the compound administered.A "excipient" refers to an inert substance added to a pharmacological composition to further facilitate the administration of a compound. , without limitation, of excipients, include calcium carbonate, calcium phosphate, various sugars and types of starch, cellulose derivatives, gelatin, vegetable oils and polyethylene glycols.The appropriate forms, in part, depend on the use or route of input, for example, oral, transdermal or by injection, these forms must allow the agent to reach a target cell, whether the target cell is is present in a particular host or in cultivation. For example, pharmacological agents or compositions injected into the blood stream must be soluble at the concentrations used. Other factors are known in the art and include considerations such as toxicity and the forms that prevent the agent or composition from exerting their effect.

It is also possible to formulate agents such as pharmaceutically acceptable salts (for example, acid addition salts) and their complexes. The preparation of said salts can facilitate the pharmacological use by altering the physical characteristics of the agent without preventing it exerting its physiological effect. Examples of useful alterations in physical properties include lowering the melting point to facilitate transmucosal administration and increasing solubility to facilitate administration of higher concentrations of the drug. For oral administration, oral administration is preferred. Alternatively, injection, for example, intramuscular, intravenous, intraperitoneal and subcutaneous, may be used. For injection, the molecules of the invention are formulated in liquid solutions, preferably in physiologically compatible regulators, such as Hank's solution or Ringer's solution. In addition, the molecules can be formulated in solid form or they can be redissolved or suspended immediately before use. It can also produce lyophilized forms. the systemic administration can be transmucosal or transdermal or the molecules can be administered orally. For transmucosal or transdermal administration, appropriate penetrators of the barrier to be permeated are used in the formulation. Such penetrators are generally well known in the art and include, for example, for transmucosal administration bile salts and fusidic acid derivatives. Additionally, detergents can be used to facilitate permeation. Transmucosal administration can be done through nasal sprays, for example, or using suppositories. For oral administration, the molecules are formulated into conventional oral dosage forms, such as capsules, tablets and tonics. For topical administration the molecules of the invention are formulated into ointments, plasters, gels or creams, as is generally known in the art. In general, a therapeutically effective amount is between about 1 nanomole and 3 nanomoles of the molecule, preferably 0.1 nmol and 1 nmole depending on its EC50 or IC50 and the age and size of the patient, as well as the associated disease or disorder with the patient In general, it is an amount between 0.1 and 50 mg / kg, preferably 0.01 to 20 mg / kg, of the animal to be treated.

EXAMPLES Examples of the synthesis of the compounds of the present invention are described below. However, it should be understood that the present invention is not restricted to the exemplified compounds. In Examples 1 to 23, the compounds represented by Figure 1 were synthesized. The compounds of the present invention represented by the formula (1) in which X is O were synthesized according to the scheme of Figure 2, using 2, 3 or 4-chlorophenol as the starting material. The compounds of the present invention represented by the formula (1) were synthesized in which X is S, according to the scheme of Figure 3, by the use of 2 or 4-chlorothiophenol as the starting material. However, methylene chloride was used as a solvent in some cases. The compounds of the present invention represented by the formula (1), in which Ar? _ Is benzothiazole or benzoxazole were synthesized according to the scheme of Fig. 4. In the examples 24 to 36 the compounds of the present invention were synthesized according to the schemes shown in figures 5 to 7.

EXAMPLE 1 SYNTHESIS OF COMPOUND 2 500 mg (3.88 mmol) of 2 -corhophenol was dissolved in 10 ml of acetonitrile. After adding 582 mg (4.28 mmol) of potassium carbonate and 1,4-dibromobutane at room temperature, the mixture was reacted while heating at 80 ° C under reflux for 3 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto, followed by extraction with separation with ethyl acetate. The organic layer thus obtained was washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. The organic layer was then concentrated under reduced pressure and the residue thus obtained was purified by silica gel column chromatography (50 g, hexane / acetone = 12: 1) to thereby give 994 mg (3.88 mmol) of the compound JL , as a colorless and transparent syrup, at a 100% yield. Then 994 mg (3.88 mmol) of compound 1 obtained above was dissolved in 18 ml of acetonitrile. After adding 652 mg (4.7 mmoles) of potassium carbonate and 1.1 g (7.28 mmoles) of (R) -3-methoxy-a-methylbenzylamine, at room temperature, the mixture was stirred while stirring at 90 ° C, under reflux for 12 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto. It was then subjected to a separating extraction with ethyl acetate and washed with saturated aqueous sodium chloride solution. The organic layer thus obtained was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (100 g, chloroform / methanol = 50: 1) to thereby give 643 mg (1.03 mmol) of compound 2, as a pale yellow, clear syrup, to 50.2% yield. MS m / z: 333. NMR with H, d: 1.34 (3H, d, J = 6.7 Hz), 1.60-1.73 (1H, m), 1.78-1.90 (1H, m), 2.48-2.62 (2H, m ), 3.75 (3H, c, J = 6.7 Hz), 3.81 (3H, s), 3.98 / (2H, t, J = 6.7 Hz), 6.77 (1H, dd, J = 7.4 Hz, J = 2.0 Hz) , 6.89-6.90 (4H, m), 7.16-7.26 (2H, m), 7.34 (1H, dd, J = 9.0 Hz, J = 2.6 Hz).

EXAMPLE 2 SYNTHESIS OF COMPOUND 4 The two steps described above were repeated, but replacing 1,4-dibromobutane with 1,5-dibromopentane to thereby give the desired compound 4. MS m / z: 347. NMR with H, d: 1.35 (3H, d, J = 6.5 Hz), 1.48-1.57 (4H, m), 1.79-1.84 (2H, m), 2.44-2.55 (2H, m ), 3.74 (1H, c, J = 6.5 Hz), 3.81 (3H, s), 4.00 (2H, t, J = 6.5 Hz), 6.77-6.79 (1H, m), 6.85-6.89 (4H, m) , 7.16-7.26 (2H, m).

EXAMPLE 3 SYNTHESIS OF THE COMPOUND 6 The two steps described above were repeated, but replacing 1, 4-dibromobutane with 1,6-dibromohexane to thereby give the desired compound 6. MS m / z: 361. 1 H NMR, d: 1.35 (3 H, d, J = 7.0 Hz), 1.34-1.39 (2H, m), 1.45-1.54 (4H, m), 1.78-1.84 (2H, m), 2.41-2.54 (2H, m), 3.73 (1H, c, J = 7.0 Hz), 3.81 (3H, s) ), 4.00 (2H, t, J = 6.5 Hz), 6.77-6.78 (1H, m), 6.85-6.90 (4H, m), 7.17-7.26 (2H, m), 7.34 (1H, dd, J = 8.0 Hz, J = 1.0 Hz).

EXAMPLE 4 SYNTHESIS OF THE COMPOUND 8 108 acetonitrile was dissolved in 548 mg (4.25 mmol) of 3-chlorophenol. After adding 652 mg (4.72 mmoles) of potassium carbonate and 0.56 ml (4.69 mmoles) of 1,4-dibromobutane at room temperature, the mixture was reacted while heating at 80 ° C for 3 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto, followed by extraction by separation with ethyl acetate. The organic layer thus obtained was washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. The organic layer was then concentrated under reduced pressure and the residue thus obtained was purified by silica gel column chromatography (50 g, hexane / acetone = 12: 1) to thereby give 846 mg (3.31 mmol) of compound 1 as a colorless and transparent syrup, at a yield of 88.3%. Next, 846 mg (3.31 mmol) of the compound 7. obtained above was dissolved in 18 ml of acetonitrile. Then 523 mg (3.78 mmol) of potassium carbonate and 550 mg (3.64 mmol) of (R) -3-methoxy-a-methylbenzylamine were added at room temperature, the mixture was stirred while heating at 90 ° C, at reflux, for 12 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto.

It was then extracted with separation with ethyl acetate and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (100 g, chloroform / methanol = 50: 1) to thereby give 481 mg (1.46 mmoles) of compound 8. as a clear and pale yellow syrup, a 45.0% yield. MS m / z: 333. NMR with H, d: 1.35. (311, d, J = 6.5 Hz), 1.57-1.67 (2H, m), 1.73-1.83 (2H, m), 2.46-2.60 (2H, m), 3.74 (1H, c), 3.81 (3H, s), 3.90 (2H, t, J = 6.5 Hz), 6.74 (1H, dd, J = 8.0 Hz, J = 2.5 Hz), 6.85-6.86 ( 1H, m), 7.5-7.18 (1H, dd, J = 2.7 Hz), 7.22-7.26 (1H, m).

EXAMPLE 5 SYNTHESIS OF COMPOUND 10 The two steps described above were repeated, but replacing 1, 4-dibromobutane with 1,5-dibromopentane to thereby give the desired compound 10. MS m / z: 347. NMR with 1H, d: 1.35 (3H, d, J = 6.0 Hz), 1.43-1.56 (4H, m), 1.72-1.77 (2H, m), 2.43-2.56 (2H, m), 3.73 (1H, c, J = 6.5 Hz), 3.81 (3H, s), 3.90 (2H, t, J = 7.0 Hz), 6.76 (1H, dd, J = 2.0 Hz, J = 8.5 Hz), 6.70-6.79 (1H, m) , 6.86-6.91 (4H, m), 7.17 (1H, dd, J = 3.0 Hz), 7.22-7.26 (1H, m).

EXAMPLE 6 SYNTHESIS OF COMPOUND 12 The two steps described above were repeated, but replacing 1, 4-dibromobutane with 1,6-dibromohexane to thereby give the desired compound 12. MS m / z: 361. 1 H NMR, d: 1.35 (3 H, d, J = 6.5 Hz), 1.33-1.56 (6H, m), 1.72-1.77 (2H, m), 3.73 (1H, m), 3.81 (3H, s), 3.90 (2H, t, J = 6.5 Hz), 6.74-6.79 (2H, m), 6.86-6.91 (4H, m), 7.17 (1H, dd, J = 8.3 Hz), 7.22-7.26 (1H, m).

EXAMPLE 7 SYNTHESIS OF COMPOUND 14 362 mg (2.82 mmoles) of 3-chlorophenol in 5 ml of acetonitrile was dissolved. After adding 429 mg (3.10 mmol) of potassium carbonate and 0.36 ml (3.01 mmol) of dibromobutane at room temperature, the mixture was reacted while heating at 80 ° C for 3 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto, followed by extraction by separation with ethyl acetate. The organic layer thus obtained was washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. The organic layer was then concentrated under reduced pressure and the residue thus obtained was purified by silica gel column chromatography (50 g, hexane / acetone = 12: 1) to thereby give 414 mg (1.62 mmoles) of compound 13. .as a colorless and transparent syrup, at a yield of 69.4%. Then 846 mg (3.31 mmol) of the compound 13 obtained above was dissolved in 18 ml of acetonitrile. Then 523 mg (3.78 mmoles) of potassium carbonate and 550 mg (3.64 mmoles) of (R) -3-methoxy-a-methylbenzylamine were added at room temperature, the mixture was stirred while heating at 90 ° C. , at reflux, for 12 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto.It was then extracted with separation with ethyl acetate and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (100 g, chloroform / methanol = 50: 1) to thereby give 481 mg (1.46 mmoles) of compound 14. as a pale yellow, clear syrup, a 45.0% yield. MS m / z: 333. NMR with H, d: 1.35 (3H, d, J = 6.5 Hz), 1.57-1.67 (2H, m), 1.73-1.83 (2H, m), 2.46-2.60 (2H, m ), 3.72-3.76 (1H, C, J = 6.5 Hz), 3.81 (3H, s), 3.89 (2H, t, J = 7.0 Hz), 6.77-6.79 (3H, m), 6.88-6.90 (2H, m), 7.19-7.26 (3H, m).

EXAMPLE 8 SYNTHESIS OF COMPOUND 16 The two steps described above were repeated, but replacing 1, 4-dibromobutane with 1,5-dibromopentane to thereby give the desired compound 16. MS m / z: 347. NMR with l ?? , d: 1.34 (3H, d, J = 6.5 Hz), 1.43-1.56 (4H, m), 1.71-1.77 (2H, m), 2.42-2.55 (2H, m), 3.72 (1H, c, J = 6.5 Hz), 3.80 (3H, s), 3.89 (2H, t, J = 6.5 Hz), 6.76-6.80 (3H, m), 6.87-6.89 (2H, m), 7.19-7.26 (3H, m).

EXAMPLE 9 SYNTHESIS OF THE COMPOUND 18 The two steps described above were repeated, but replacing 1, 4-dibromobutane with 1,6-dibromohexane to thereby give compound JL8. wanted. MS m / z: 361. NMR with 1H, d: 1.35 (3H, d, J = 7.0 Hz), 1.32-1.56 (6H, m), 1.71-1.77 (2H, m) 2.41-2.53 (2H, m) , 3.73 (1H, m), 3.81 (3H, s), 3.89 (2H, t, J = 7.0 Hz), 6.77-6.81 (3H, m), 6.88-6.89 (3H, m), 7.19-7.26 (3H , m).

EXAMPLE 10 SYNTHESIS OF THE COMPOUND 20 • 330 mg (2.28 mmol) of 2-chlorothiophenol was dissolved in 6.5 ml of methylene chloride. After adding 0.35 ml (2.51 mmoles) of triethylamine and 0.23 ml (2.26 mmoles) of 1,3-dibromopropane, at room temperature, the mixture was reacted while heating at 45 ° C under reflux for 6 hours. After the reaction was completed, it was added dropwise 0.30 ml (2.15 mmole) of triethylamine, in the reaction, at room temperature. Then 350 mg (2.31 mmol) of (R) -3-methoxy-a-methylbenzylamine was added and the resulting mixture was stirred while heating at 90 ° C under reflux for 12 hours. After the. reaction was allowed to rest reaction mixture at room temperature and water was added. It was then subjected to a separating extraction with ethyl acetate and washed with a saturated aqueous solution of sodium chloride.

The organic layer thus obtained was dried over sodium sulfate and concentrated under reduced pressure. The waste was purified well obtained by column chromatography on silica gel (50 g, chloroform / methanol = 65: 1) to thereby give 102 mg (0.304 mmol) of compound 20. as a clear and pale yellow syrup, at a total yield of two steps of 13.2%.

MS m / z: 335. RMN with 1H, d: 1.35 (3H, d, J = 6.7 Hz), 1.79-1.86 (2H, m) 2.55-2.69 (2H, m), 2.91-3.03 (2H, m), 3.74 (1H, c, J = 6.7 Hz), 3.81 (3H, s), 6.78 (1H, dd J = 2.5 Hz, J = 8.0 Hz), 6.88-6.90 (2H, m), 7.07-7.11 (1H, m), 7.18-7.26 (3H, m), 7.34 (1H, dd, J = 8.0 Hz, J = 1.2 Hz).

EXAMPLE 11 SYNTHESIS OF THE COMPOUND 22 The two steps described above were repeated, but replacing 1, 3-dibromopropane with 1,4-dibromopentane to thereby give the desired compound 22. MS m / z: 349. NMR with H d: 1.33 (3H, d, J = 6.5 Hz), 1.58-1.72 (4H, m), 2.43-2.56 (2H, m), 2.90 (2H, t, J = 7.5 Hz), 3.72 (1H, c, J = 6.5 Hz), 3.80 (3H, s), 6.76-6.78 (1H, m), 6.87-6.88 (2H, m), 7.07-7.10 (1H, m), 7.18-7.26 (3H, m), 7.35 (1H, dd, J = 8.0 Hz).

EXAMPLE 12 S NTESIS OF THE COMPOUND 24 The two steps described above were repeated, but replacing 1, 3-dibromopropane with 1,5-dibromopentane to thereby give the desired compound 24. MS m / z: 363. 1 H NMR: 1.34 (3 H, d, J = 7.0 Hz), 1.42-1.55 (4H, m), 1.64-1.72 (2H, m), 2.40-2.53 (2H, m), 2.90 (2H, t, J = 7.5 Hz), 3.72 (1H, c, J = 7.0 Hz), 3.81 (3H, s), 6.77-6.79 (1H, m), 6.87-6.91 (2H, m), 7.07-7.10 (1H, m ), 7.18-7.26 (3H, m), 7. 35 (1H, dd, J = 8.0 Hz).

EXAMPLE 13 SYNTHESIS OF THE COMPOUND 26 The two steps described above were repeated, but replacing 1, 3 -dibromopropane with 1,6-dibromohexane to thereby give the desired compound 26. MS m / z: 377. NMR with H d: 1.34 (3H, d, J = 6.5 Hz), 1.41-1.50 (4H, m), 1.64-1.70 (2H, m), 2.90 (2H, t, J = 7.5 Hz), 3.72 (1H, c, J = 6.5 Hz), 3.81 (3H, s), 6.77-6.79 ( 1H, m), 6.88-6.89 (2H, m), 7.06-7.11 (1H, m), 7.19-7.26 (3H, m), 7.35 (1H, dd, J = 8.0 Hz).

EXAMPLE 14 SYNTHESIS OF THE COMPOUND 28 540 mg (3.77 mmoles) of 4-chlorothiophenol was dissolved in 10 ml of methylene chloride. After adding 1.60 ml (11.5 mmoles) of triethylamine and 0.63 ml (4.10 mmoles) of 1,3-dibromopropane at room temperature, the mixture was reacted while heating at 45 ° C under reflux for 3 hours.

After the reaction was complete, the methylene chloride was removed all at once under reduced pressure and the residue was dissolved in 9 ml of acetonitrile. Then 500 mg was added (3.62 mmoles) of potassium carbonate at room temperature, and 350 mg (2.31 mmol) of (R) -3-methoxy-a-methylbenzylamine was added dropwise. The resulting mixture was then stirred while heating at 90 ° C under reflux for 12 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto. It was then subjected to a separating extraction with ethyl acetate and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (75 g, chloroform / methanol = 65: 1) to thereby give 397 mg (1.13 mmol) of compound 2_8 as a clear and pale yellow syrup, to a Total yield in the two steps of 33.1%. MS m / z: 335. NMR with ^ -H, d: 1.33 (3H, d, J = 7.0 Hz), 1.72-1.78 (2H, m) 2.50-2.55 (1H, m), 2.56-2.64 (1H, m), 2.86-2.97 (2H, m), 3.71 (1H, c, J = 7.0 Hz), 3.81 (3H, s), 6.77-6.79 (1H, m), 6.85-6.89 (2H, m), 7.22 -7.25 (4H, m).

EXAMPLE 15 SYNTHESIS OF THE COMPOUND 30 The two steps described above were repeated, but replacing 1, 3 -dibromopropane with 1,4-dibromobutane to thereby give the desired compound 3_0. MS m / z: 363. NMR with ^ -H d: 1.35 (3H, d, J = 6.7 Hz), 1.39-1.49 (2H, tt, J = 7.5 Hz), 2.39-2.44 (1H, m), 2.86 (2H, t, J = 7.3 Hz), 3. 72 (1H, c, J = 6.7 Hz), 3.81 (3H, s), 6.77-6.79 (1H, m), 6.87-6.88 (2H, m), 7.20-7.26 (5H, m).

EXAMPLE 16 SYNTHESIS OF THE COMPOUND 32 The two steps described above were repeated, but replacing 1, 3-dibromopropane with 1, 5-dibromopentane to thereby give the desired compound 32. MS m / z: 377. NMR with R d: 1.34 (3H, d, J = 6.7 Hz), 1.27-1.48 (4H, m), 1.60 (2H, tt, J = 7.5 Hz), 2.39-2.44 (1H , m), 2.46-2.51 (1H, m), 2.85 (2H, t, J = 7.3 Hz), 3.72 (1H, c, J = 6.7 Hz), 3.81 (3H, s), 6.76-6.79 (1H, m), 6.87-6.89 (2H, m), 7.21-7.26 (5H, m).

EXAMPLE 17 SYNTHESIS OF THE COMPOUND 34 The two steps described above were repeated, but replacing 1, 3 -dibromopropane with 1,6-dibromohexane to thereby give the desired compound 34. MS m / z: 349. NMR with XH d: 1.34 (3H, d, J = 6.5 Hz), 1.52-1.67 (6H, m), 2.40-2.45 (1H, m), 2.48-2.53 (1H, m) , 2.86 (2H, t, J = 7.0 Hz), 3.71 (1H, c, J = 6.5 Hz), 3.80 (3H, s), 6.76-6.79 (1H, m), 6.86-6.88 (2H, m).

EXAMPLE 18 SYNTHESIS OF THE COMPOUND 36 440 mg (2.63 mmoles) of 2-mercaptobenzothiazole was dissolved in 9 ml of methylene chloride. After adding 1.1 ml (7.89 mmoles) of triethylamine and 0.35 ml (2.93 mmoles) of 1,4-dibromobutane at room temperature, the mixture was reacted at the same temperature for 12 hours. After the reaction was complete, the methylene chloride was removed all at once under reduced pressure and the residue was dissolved in 8 ml of acetonitrile. Then 800 mg (5.79 mmoles) of potassium carbonate was added at room temperature, and 320 mg (2.12 mmol) of (R) -3-methoxy-a-methylbenzylamine was added dropwise. The resulting mixture was then stirred while heating at 90 ° C under reflux for 12 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto. It was then subjected to a separating extraction with ethyl acetate and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (70 g; chloroform / methanol = 50: 1) to thereby give 267 mg (0.72 mmol) of compound 36 as a clear, pale yellow syrup, at a total yield in the two steps of 27.1%.

MS m / z: 372. NMR with ^ -H, d: 1.34 (3H, d, J = 6.5 Hz), 1.61-1.68 (2H, m) 1.82-1.88 (2H, m), 2.46-2.60 (2H, m), 3.32 (2H, t, J = 7.5 Hz), 3.73 (1H, c, J = 6.5 Hz), 3.80 (3H, s), 6.76-6.78 (1H, m), 6.87-6.89 (2H, m), 7.21-7.30 (2H, m ), 7.38-7.42 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.84 (1H, d, J = 8.0 Hz).

EXAMPLE 19 SYNTHESIS OF THE COMPOUND 38 409 mg (2.45 mmol) of 2-mercaptobenzothiazole was dissolved in 4 ml of acetonitrile. After adding 690 mg (4.99 mmoles) of potassium carbonate and 0.32 ml (2.68 mmoles) of 1,5-dibromopropane at room temperature, and the mixture was stirred at the same temperature for 1 hour. After the reaction was completed, 420 mg (3.04 mmol) of potassium carbonate was added, and 260 mg was added dropwise. (1.72 mmol) of (R) -3-methoxy-a-methylbenzylamine. The resulting mixture was then stirred while heating at 90 ° C under reflux for 12 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto. It was then subjected to a separating extraction with ethyl acetate and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over sodium sulfate and concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (50 g; chloroform / methanol = 50: 1) to thereby give 215 mg (0.57 mmol) of compound 38., as a clear pale yellow syrup, at a total yield in both steps of 45.0%. MS m / z: 386. NMR with H d: 1.33 (3H, d, J = 6.5 Hz), 1.44-1.56 (4H, m), 1.78-1.84 (2H, m), 2.42-2.51 (2H, m) , 3.32 (2H, t, J = 7.3 Hz), 3.71 (1H, c, J = 6.5 Hz), 3.81 (3H, s), 6.76-6.78 (1H, m), 6.86-6.88 (2H, m), 7.22 (1H, dd, J = 8.0 Hz), 7.26-7.30 (1H, m), 7.39-7.42 (1H, m), 7.74 (1H, d, J = 7.5 Hz), 7.85 (1H, d, J) 8.5 Hz).

EXAMPLE 20 SYNTHESIS OF THE COMPOUND 40 The two steps described above were repeated, but replacing 1, 5-dibromopentane with 1,6-dibromohexane to thereby give the desired compound 40. MS m / z: 409. NMR with XH d: 1.34 (3H, d, J = 6.5 Hz), 1.43-1.50 (6H, m), 1.80 (2H, tt, J = 7.5 Hz), 2.40-2.52 (2H, m), 3.32 (2H, t, J = 7.8 Hz), 3.72 (1H, c, J = 6.5 Hz) , 3.81 (3H, s), 6.76-6.78 (1H, m), 6.87-6.89 (2H, m), 7.22-7.30 (2H, m), 7.40 (1H, dd, J = 7.5 Hz), 7.74 (1H, d, J = 7.5 Hz), 7.85 (1H, d, J = 8.0 Hz).

EXAMPLE 21 SYNTHESIS OF COMPOUND 42 467 mg (3.09 mmol) of mercaptobenzothiazole was dissolved in 7 ml of acetonitrile. After adding 527 mg (3.81 mmoles) of potassium carbonate and 0.41 ml (3.43 mmoles) of 1,4-dibromobutane at room temperature, and stirring the mixture at the same temperature for 12 hours. After the reaction was completed, 4.4 ml of acetonitrile and 420 mg (3.04 mmol) of potassium carbonate were added again, and 320 mg (2.12 mmol) of (R) -3-methoxy-a-methylbenzylamine was added dropwise. The resulting mixture was then stirred while heating at 90 ° C under reflux for 12 hours. After the reaction was completed, the reaction mixture was allowed to stand at room temperature and water was added thereto. It was then subjected to a separating extraction with ethyl acetate and washed with a saturated aqueous solution of sodium chloride.

The organic layer thus obtained was dried over sodium sulfate. The organic layer was then concentrated under reduced pressure and the residue thus obtained was purified by silica gel column chromatography (50 g, chloroform / methanol = 60: 1) to thereby give 147 mg (0.41 mmol) of compound 42 ., as a clear pale yellow syrup, at a total yield in both steps of 13.4%. MS m / z: 356. NMR with XH d: 1.35 (3H, d, J = 6.7 Hz), 1.61-1.68 (2H, m), 1.81-1.89 (2H, m), 2.46-2.59 (2H, m) , 3.28 (2H, t, J = 7.5 Hz), 3.73 (1H, c, J = 6.7 Hz), 3.80 (3H, s), 6.76-6.78 (1H, m), 6.88-6.89 (2H, m), 7.21-7.28 (3H, m), 7.42 (1H, d, J = 8.0 Hz), 7.58 (1H, d, J = 8.0 Hz) EXAMPLE 22 SYNTHESIS OF THE COMPOUND 44 The two steps described above were repeated, but replacing 1, 4-dibromobutane with 1,5-dibromopentane to thereby give the desired compound 44. MS m / z: 370. NMR with XH d: 1.33 (3H, d, J = 6.8 Hz), 1.46-1.56 (4H, m), 1.81 (2H, m), 2.41-2.53 (2H, m), 3.29 (2H, t, J = 7.3 Hz), 3.72 (1H, c, J = 6.8 Hz), 3.81 (3H, s), 6.76-6.78 (1H, m), 6. 86-6.89 (2H, m), 7.20-7.29 (1H, d, J = 8.0 Hz), 7.42 (1H, d, J = 8.0 Hz), 7.59 (1H, d, J = 7.5 Hz).

EXAMPLE 23 SYNTHESIS OF THE COMPOUND 46 The two steps described above were repeated, but replacing 1, 4-dibromobutane with 1,6-dibromohexane to thereby give the desired compound 46. MS m / z: 384. NMR with XH d: 1.34 (3H, d, J = 6.5 Hz), 1.32-1.62 (6H, m), 1.81 (2H, ce, J = 7.5 Hz), 2.40-2.52 (2H , m), 3.29 (2H, t, J = 7.5 Hz), 3.72 (1H, c, J = 6.5 Hz), 3.81 (3H, s), 6.76-6.79 (1H,), 6.87-6.89 (2H, m ), 7.21-7.29 (3H, m), 7.43 (1H, d, J = 8.0 Hz), 7.59 (1H, d, J = 7.5 Hz).

EXAMPLE 24 SYNTHESIS OF COMPOUNDS 52 AND 53 To a solution of 25 g (122.4 mmol) of 5- 5-methoxigramin 4_7 in 500 ml of ethanol was added 21.5 g (568.3 mmol, 4.6 molar equivalents) of sodium tetrahydroborate, and * The mixture was stirred with heating for 5.5 hours.

After the reaction was completed, ammonium chloride was added to the reaction mixture. Then the mixture was stirred at room temperature, poured into water and extracted with ^ ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained by column chromatography (silica gel, chloroform-ethyl acetate) to give in that way 17. 31 g (87.8%) of colorless prismatic crystals 48 .. f »To a solution of 17.3 g of compound 4_8 (107.5 mmoles) in 500 ml of absolute tetrahydrofuran was added 20 g (500 mmol, 4.6 molar equivalents) of sodium hydride at 52. 9% and the reaction mixture was stirred at room temperature for 1.5 hours. Then 30 g was added (d = 1. 333, 157.4 mmoles, 1.5 molar equivalents) of tosyl chloride and the resulting mixture was stirred at the temperature atmosphere for 6 hours. After completion of the reaction, the reaction mixture was poured into water while cooling with ice and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by column chromatography (silica gel, m chloroform-ethyl acetate) to thereby give 36.8 g (82.8%) of colorless prismatic crystals 49. 17 ml (d = 2698, 183.1 mmol) of boron tribromide to a solution of 28.43 g (90.25 mmoles) of compound 4_9 in 800 ml of methylene chloride at an internal temperature of 0 to 5 ° C. The mixture was stirred at room temperature for 4 hours. After completion of the reaction, the reaction mixture was poured into water while cooling with ice and extracted with methylene chloride. The methylene chloride layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate.

W? After distilling off the solvent under reduced pressure, the crystals obtained were purified by Column chromatography (silica gel: 400 g, chloroform-methanol = 1000: 1) to thereby give 16.46 (60.6 &) of colorless prismatic crystals 50. To a solution of 16.46 g (54.7 mmol) of compound 50 in 300 ml of acetonitrile, 11.2 ml (d = 1333, 109.5 mmol, 2.0 molar equivalents) of 1,3-dibromopropane and 22 g (159.2 mmol, 2.9 molar equivalents) of potassium carbonate, and the resulting mixture was stirred with heating at an external temperature of 60 ° C, for 2.5 hours . After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained crystals were purified by means of column chromatography (silica gel, n-hexane-acetone) to thereby give 18.34 g (79.7%) of colorless prismatic crystals 51. A a solution of 200 mg (0.48 mmol) of compound 51. in 3 ml of acetonitrile, was added 142.52 mg (0.95 mmol, 2.0 molar equivalents) of (R) -3-methoxy-a-methylbenzylamine and 131. 3 mg (0.95 mmol, 2.0 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After the solvent was distilled off under reduced pressure, the obtained yellowish-brown residue was dissolved in 3 ml of ethanol and 1 ml of a 35% aqueous solution of potassium hydroxide was added. The mixture was then stirred with heating at an external temperature of 80 ° C for 2 hours. After completing the reaction, the reaction mixture was concentrated, poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the residue thus obtained was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 122.6 mg (93.8%) of a colorless oil. .. MS m / z: 338 (M +). NMR with 1H d: 1.36 (3H, d, J = 6.7 Hz, CH3), 1.97 (2H, dt, J = 6.7, 12.8 Hz, CH2), 2.30 (1H, s, CH3), 2.67 (1H, dt, J = 6.7, 11.6 Hz, CH2), 2.74 (1H, dt, J = 6.7, 13.4 Hz, CH2), 3.77 (1H, c, J = 6.7 Hz, CH), 3.78 (3H, s, OCH3), 4.07 (2H, m, CH2), 6.78 (1H, dd, J = 1.8, 7.9 Hz, Cg-H), 6.82 (1H, dd, J = 1.8, 7.9 Hz, C6'-H), 6.90 (2H, d , J = l.8 Hz, C2-H), 6.91 (1H, d, J = 7.9 Hz, C4-H), 6.94 (1H, s, C2'H), 6.99 (1H, d, J = l .8 Hz, C4'-H), 7.21 (1H, d, J = 7.9 Hz, C? -H), 7.23 (1H, t, J = 7.9 Hz, C5-H), 7.81 (1H, s, NH). To a solution of 200 mg (0.48 mmol) of compound .51 in 3 ml of acetonitrile was added 162.7 mg (0.95 mmol, 2.0 molar equivalents) of (R) -1- (1-naphthyl) ethylamine and 131.3 mg (0.95 mmol). , 2.0 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was completed, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and washed over sodium sulfate. After the solvent was distilled off under reduced pressure, the yellowish brown residue obtained was dissolved in 1 ml of ethanol and • added 1 ml of an aqueous 35% potassium hydroxide solution. The mixture was stirred with heating at an external temperature of 80 ° C for 2 hours. After the reaction was complete, the reaction mixture was concentrated, poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and a concentrated aqueous solution of sodium chloride and dried over sodium sulfate. After ^ Remove the solvent by distillation under reduced pressure, the residue obtained was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 122.6 (93.8%) of a colorless oil 53. 15 MS m / z: 358 (M +). NMR with H d: 1.53 (3H, d, J = 6.7 Hz, CH3), 2.03 (2H, dt, J = 6.7, 12.8 Hz, CH2), 2.30 (3H, s, CH3), 2.83 (2H, dt, J = 6.7, 12.8 Hz, CH2), 4.12 (2H, dt, J = 3.1, 9.2 Hz, CH2), 4.68 (1H, c, J = 6.7 Hz, CH), 6.83 (1H, dd, J = 1.8, 9.2 Hz, C2-H), 6.94 (1H, s, C2 * -H), 7.01 (1H, d, J = 1.8 Hz, C4 '-H), 7.21 (1H, d, J = 7.9 Hz, C4-H), 7.48 (1H, t, J = 7.9 Hz, C3-H), 7.49 (1H, t, J = 7.9 Hz, Cg-H), 7.50 (1H, t, J = 7.9 Hz, C7-H), 7.68 (1H, d, J = 7.9 Hz, C5-H), 7.75 (1H, d, J = 7.9 Hz, C8-H), 7.82 (1H, s, NH), 7.88 (1H, dd, J = 1.8, 7.9 Hz, C • -H), 8.21 (1H, d, J = 7.9 Hz, C7'-H).

EXAMPLE 25 SYNTHESIS OF THE COMPOUND 56 To a solution of 500 mg (2.74 mmoles) of 9-hydroxyfluorene 54 in 5 ml of toluene was added 0.273 ml (d = 1.537, 3.02 mmoles, 1.1 molar equivalents) of 3-bromo-1-propanol and 5.1 mg (0.027 mmol)., 0.01 molar equivalents) of p-toluenesulfonic acid and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the resulting residue was purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 723.4 mg (87%) of a colorless oil 55. To a solution of 200 mg (0.66 mmol) of compound 55 in 3 ml of acetonitrile, 148.5 mg (0.99 mmol, 1.5 molar equivalents) of (R) -3-methoxy-a-methylbenzylamine and 136.8 mg (0.99 mmol) were added. , 1.5 molar equivalents) of potassium carbonate, and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 216.6 mg (88.0%) of a colorless oil 56. MS m / z: 373 (M). NMR with 1H d: 1.30 (3H, d, J = 6.7 Hz, CH3), 1.67 (2H, dt, J = 6.7, 13.4 Hz, CH2), 2.49 (1H, dt, J = 6.7, 14.0 Hz, CH2) , 2.56 (1H, dt, J = 6.7, 11.6 Hz, CH2), 3.21 (2H, t, J = 6.7 Hz, CH2), 3.69 (1H, c, J = 6.7 Hz, CH), 3.78 (3H, s , OCH3), 5.59 (1H, s, CH), 6.76 (1H, dd, J = 1.8, 7.9 Hz, Cg-H), 6.85 (1H, d, J = 1.8 Hz, C2-H), 6.87 (1H, d, J = 7.9 Hz, C4-H), 7.21 (1H, t, J = 7.9 Hz, C5-H), 7.28 (2H, t, J = 7.9 Hz, C3 ', Cg' -H), 7. 37 (2H, t, J = 7.9 Hz, C2 ', C7' -H), 7.53 (1H, d, J = 7.9 Hz, C4 '- H), 7.55 (1H, d, J = 7.9 Hz, C5' -H), 7.65 (2H, d, J = 7.9 Hz, Cx •, C8'-H), 7.81 (1H, s, NH).

EXAMPLE 26 SYNTHESIS OF THE COMPOUND 59 To a solution of 200 mg (1.1 mmol) of 2-hydroxyfluorene 57. in 3 ml of acetonitrile was added 0.22 ml (d = 1333, 2.2 mmoles, 2.0 molar equivalents) of 1,3-dibromopropane and 182.0 mg (1.32 mmol, 1.2 molar equivalents) of potassium carbonate, and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After the solvent was distilled off under reduced pressure, the crystals obtained were purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 202.4 mg (73.3%) of colorless prismatic crystals 58. NMR with XH d: 2.35 (2H, dt, J = 6.1, 12.2 Hz, CH2), 3.64 (2H, t J = 6.1 Hz, CH2), 3.86 (2H, s, C9-H), 4.17 (2H, t , J = 6.1 Hz, CH2), 6.93 (1H, dd, J = 1.8, 7.3 Hz, C2-H), 7.11 (1H, d, J = 1.8 Hz, C4-H), 7.23 (1H, t, J = 7.3 Hz, Cg-H), 7.34 (1H, t, J = 7.3 Hz, C7-H), 7.50 (1H, d, J = 7.3 Hz, C? -H), 7.67 (1H, d, J = 6.7 Hz, C8-H), 7.69 (1H, t, J = 6.7 Hz, C5-H). To a solution of 100 mg (0.33 mmol) of compound 58. in 3 ml of acetonitrile was added 49.5 mg (0.33 mmol, 1.0 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 54.7 mg (0.40 mmol, 1.2 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 216.6 mg (88.0%) of a colorless oil 59. MS m / z: 373 (M +). NMR with H d: 1.36 (3H, d, J = 6.7 Hz, CH3), 1. 96 (2H, m, CH2), 2.65 (2H, dt, J = 6.7, 11.6 Hz, CH2), 2.73 (2H, dt, J = 6.7, 12.2 Hz, CH2), 3.77 (1H, c, J = 6.7 Hz, CH), 3.78 (3H, s, 0CH3), 3.85 (2H, s, CH2), 4.07 (2H, c, J = 5.5 Hz, C9- H2), 6.77 (1H, dd, J = 1.8, 7.3 Hz, Cg-H) , 6.89 (1H, d, J = 1.2 Hz, C2-H), 6.90 (1H, d, J = 7.3 Hz, C4-H), 6.90 (1H, d, J = 7.3 Hz, C2'-H), 7.06 (1H, s, C4'-H), 7.22 (1H, t, J = 7.3 Hz, C5-H), 7.22 (1H, t, J = 7.3 Hz, Cg'-H) , 7.33 (1H, t, J = 7.3 Hz, C7 '-H), 7.49 (1H, d, J = 7.3 Hz, Ci'-H), 7.65 (1H, d, J = 7.3 Hz, C8'H), 7.68 (1H, d, J = 7.3 Hz, C5'-H).

EXAMPLE 27 SYNTHESIS OF THE COMPOUND 62 To a solution of 500 mg (3.89 mmoles) of o-chlorophenol 60. in 3 ml of acetonitrile, 0.39 ml (d = 1989, 3.89 mmoles, 1.0 molar equivalents) of 1,3-dibromopropane and 591.2 mg (4.28 mmoles) were added. , 1.1 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C, for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 824.0 mg (84.9%) of a colorless oil 61. To a solution of 200 mg (0.66 mmol) of compound 61 in 3 ml of acetonitrile was added 148.5 mg (0.99 mmol, 1.5 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 136.8 mg (0.99 mmol)., 1.5 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 222.6 mg (87.1%) of a colorless oil 62. MS m / z: 319 (M +). NMR with H d: 1.37 (3H, d, J = 6.7 Hz, CH3), 1.99 (2H, dt, J = 6.7, 12.2 Hz, CH2), 2.67 (1H, dt, J = 6.7, 13.4 Hz, CH2) , 2.75 (1H, dt, J = 6.7, 11.6 Hz, CH2), 3.75-3.79 (1H, m CH), 3.78 (3H, s, OCH3), 4.09 (2H, dt, J = 1.8, 6.1 Hz, CH2 ), 6.77 (1H, dd, J = 1.8, 7.3 Hz, Cg-H), 6.89 (1H, t, J = 7.9 Hz, C4-H), 6.90 (1H, d, J = 1.8 Hz, C2-H ), 6.90 (1H, d, J = 7.9 Hz, C4-H), 6.90 (1H, d, C3'H), 7.20 (1H, dt, J = 1.8, 7.3 Hz, C5'H), 7.22 (1H, t, J = 7.9 Hz, C5-H), 7.4 (1H, dd, J = 1.8, 7.9 Hz, Cg • -H).

EXAMPLE 28 SYNTHESIS OF THE COMPOUND 65 To a solution of 500 mg (3.89 mmoles) of m-chlorophenol 63_ in 3 ml of acetonitrile, 0.39 ml (d = 1989, 3.89 mmoles, 1.0 molar equivalents) of 1,3-dibromopropane and 591.2 mg (4.28 mmoles, 1.1 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C, for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 884.2 mg (91.1%) of a colorless oil 64 .. A a solution of 200 mg (0.66 mmol) of compound 64. in 3 ml of acetonitrile was added 148.5 mg (0.99 mmol, 1.5 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 136.8 mg (0.99 mmol, 1.5 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 229.3 mg (89.7%) of a colorless oil 65. MS m / z: 319 (M +). NMR with ^ H d: 1.35 (3H, d, J = 6.7 Hz, CH3), 1.88-1.96 (2H, m, CH2), 2.61 (1H, dt, J = 6.7, 11.6 Hz, CH2), 2.70 (1H , dt, J = 6.7, 11.6 Hz, CH2), 3.75 (1H, c, J = 6.7 Hz, CH), 3. 80 (3H, s, OCH3), 3.96-4.04 (2H, m, CH2), 6.75 (1H, d, J = 7.9 Hz, Cg-H), 6.78 (1H, d, J = 7.9 Hz, Cg-H), 6.88 (1H, s), 6.88-6.92 (3H, m), 7.17 (1H, t, J = 7.9 Hz, C5 '-H), 7.23 (1H, t, J = 7.9 Hz, C5-H).

EXAMPLE 29 SYNTHESIS OF THE COMPOUND 68 To a solution of 500 mg (3.89 mmol) of p-chlorophenol 66_ in 3 ml of acetonitrile, 0.39 ml (d = 1989, 3.89 mmol, 1.0 molar equivalent) of 1,3-dibromopropane and 591.2 mg (4.28 mmol, 1.1 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C, for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 876.5 mg (90.3%) of a colorless oil 67. To a 200 mg solution (0.66 mmol) of compound 67 in 3 ml of acetonitrile was added 148.5 mg (0.99 mmol, 1.5 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 136.8 mg (0.99 mmol, 1.5 molar equivalent) ) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the residue obtained was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 293.1 mg (87.2%) of a colorless oil 68. MS m / z: 319 (M +). NMR with 1H d: 1.35 (3H, d, J = 6.4 Hz, CH3), 1.91 (2H, dt, J = 6.4 Hz, CH2), 2.67 (2H, dt, J = 2.4, 6.4 Hz, CH2), 3.75 (1H, c, J = 6.4 Hz, CH), 3.79 (3H, s, OCH3), 3.98 (2H, t, J = 6.4 Hz, CH2), 6.70-6.91 (5H, m), 7.14 (3H, m ).

EXAMPLE 30 SYNTHESIS OF THE COMPOUND 71 To a solution of 500 mg (2.71 mmoles) of 3-hydroxybenzofuran 69. in 5 ml of acetonitrile, 0.55 ml (d = 1989, 5.43 mmoles, 2.0 molar equivalents) of 1,3-dibromopropane and 750.1 mg (5.43 mmoles) were added. , 2.0 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C, for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 804.3 mg (77.0%) of a colorless oil 70. A 800 mg solution (2.62 mmol) of compound 70. in 5 ml of acetonitrile was added 590.2 mg (3.93 mmol, 1.5 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 543.7 mg (3.93 mmol, 1.5 equivalents) molars) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 880.8 mg (89.5%) of a colorless oil 71. MS m / z: 375 (M +). NMR with H d: 1.38 (3H, d, J = 6.7 Hz, CH3), 2.01 (2H, m, CH2), 2.70 (1H, dt, J = 6.7, 14.0 Hz, CH2), 2.77 (1H, dt, J = 6.7, 13.4 Hz, CH2), 3.80 (1H, c, J = 6.7 Hz, CH), 3.80 (3H, s, OCH3), 4.10-4.17 (2H, m, CH2), 6.79 (1H, dd, J = 1.8, 7.3 Hz, Cg-H), 6.91 (1H, d, J = 1.8 Hz, C2-H), 6.92 (1H, dJ = 7.3 Hz, C4-H), 7.02 (1H, dd, J = 2.5, 8.6 Hz, C3'H), 7.24 (1H, t, J = 7.3 Hz, C5-H), 7.33 (1H, t, J = 7.3 Hz, C '-H), 7.41 ((1H, d, J = 2.5 Hz, Cx'-H), 7.45 (1H, dt, J = 1.2, 7.3 Hz, C7 '-H), 7.46 (1H, d, J = 7.3 Hz, C5'-H), 7.55 (1H, d, J = 8.6 Hz, C4 '-H), 7.91 (1H, d, J = 7.3 Hz, C8'-H).

EXAMPLE 31 SYNTHESIS OF THE COMPOUND 74 To a solution of 300.0 mg (2.16 mmol) of 2-naphthol 72 in 3 ml of absolute tetrahydrofuran, 300 ml was added (d = 1. 537, 2.16 mmoles, 1.0 molar equivalents) of 3-bromo-1-propoanol and 611. 1 mg (2.37 mmol, 1.1 molar equivalents) of triphenylphosphine. A solution of 0.41 ml was then added (d = 1.106, 2.37 mmol, 1.1 molar equivalents) of DEAD in 3 ml of absolute tetrahydrofuran and the resulting mixture was stirred at room temperature for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the residue was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 551.8 mg (100%) of a colorless oil 73 .. A a solution of 200 mg (0.75 mmol) of compound 73. in 5 ml of acetonitrile was added 169.8 mg (1.13 mmol, 1.5 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 156.5 mg (1.13 mmol, 1.5 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After the solvent was distilled off under reduced pressure, the residue obtained was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 230.8 mg (91.3%) of a colorless oil 74. MS m / z: 335 (M +). NMR with 1H d: 1.41 (3H, d, J = 6.7 Hz, CH3), 2.13 (2H, dt, J = 6.7, 12.8 Hz, CH2), 2.73 (1H, dt, J = 6.7, 11.6 Hz, CH2) , 2.85 (1H, dt, J = 6.7, 11.6 Hz, CH2), 3.79 (3H, s, OCH3), 3.83 (1H, c, J = 6.7 Hz, CH), 4.23 (2H, dt, J = 1.2 6.1 , Hz, CH2), 6.80 (1H, dd, J = 2.4, 7.9 Hz, Cg-H), 6.83 (1H, d, J = 7.3 Hz, C2'-H), 6.92 (1H, d, J = 2.4 Hz, C2-H), 6.93 (1H, d, J = 7.9 Hz, C4-H), 7.24 (1H, d, J = 7.9 Hz, C4-H), 7.24 (1H, t, J = 7.9 Hz, C5-H), 7.39 (1H, t, J = 7.9 Hz, Cg '-H), 7.45 (1H, t, J = 7.9 Hz, C4'-H), 7.48 (1H, dd, J = 1.2, 7.9 Hz, C3 '-H), 7.52 (1H, dt, J = 1.2, 7.9 Hz, C7'-H), 7.83 (1H, d, J = 7.9 Hz, C5'H), 8.22 (1H, d, J = 7.9 Hz, C8 '-H).

EXAMPLE 32 SYNTHESIS OF THE COMPOUND 77 To a solution of 300 mg (1.87 mmol) of 2-naphthalenethiol 75. in 5 ml of methylene chloride was added 0.23 ml (d = 1989, 2.25 mmol, 1.2 molar equivalents) of 1,3-dibromopropane and 0.31 mg. d = 0.726, 2.25 mmoles, 1.2 molar equivalents) of triethylamine and the resulting mixture was stirred with heating at an external temperature of 40 ° C, for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with 5% aqueous hydrochloric acid solution, with water and with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 241.3 mg (45.9%) of a colorless oil 76. A 241 mg solution (0.86 mmol) of compound 76. in 5 ml of acetonitrile was added 193.0 mg (1.29 mmol, 1.5 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 177.8 mg (1.29 mmol, 1.5 equivalents) molars) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the residue obtained was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 209.8 mg (67.9%) of a colorless oil 77. MS m / z: 351 (M +). NMR with H d: 1.38 (3H, d, J = 6.7 Hz, CH3), 2. 01 (2H, dt, J = 6.7 Hz, CH2), 2.73 (2H, dt, J = 6.7, 25.0 Hz, CH2), 3.80 (1H, c, J = 6.7 Hz, CH), 3.80 (3H, s, OCH3), 4.13 (2H, m, CH2), 6.79 (1H, dd, J = 1.8, 7.3 Hz, Cg-H), 6.91 (1H, d, J = 1.2 Hz, C2-H), 6.92 (1H, dJ = 7.3 Hz, C4-H), 7.02 (1H, dd, J = 2.5, 7.3 Hz, C3 • -H), 7.24 (1H, t, J = 7.3 Hz, C5-H), 7.33 (1H, t , J = 7.3 Hz, Cg'-H), 7.41 ((1H, d, J = 2.5 Hz, C? _ '-H), 7.45 (1H, dt, J = 1.2, 7.3 Hz, C7' -H) , 7.46 (1H, d, J = 7.3 Hz, C4 '-H), 7.55 (1H, d, J = 7.3 Hz, C5'-H), 7.91 (1H, d, J = 7.3 Hz, C8'H ).

EXAMPLE 33 SYNTHESIS OF THE COMPOUND 80 To a solution of 500 mg (3.76 mmoles) of 3-hydroxyindole .78. in 5 ml of acetonitrile, 833.9 mg (d 1. 989, 4.13 mmoles, 1.1 molar equivalents) of 1,3-dibromopropane and 570.9 mg (4.13 mmoles, 1.1 molar equivalents) of potassium carbonate and the resulting mixture c was stirred with heating at an external temperature of 60 ° C, for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling out the At reduced pressure, the residue obtained was purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 586 mg (61.4%) of a colorless oil 79. • NMR with H d: 2.33 (2H, dt, J = 6.1, 12.2 Hz, CH2), 3.63 (2H, t, J = 6.1 Hz, CH2), 4.13 (2H, t, J = 6.1 Hz, CH2), 6.47 (1H, t, J = 2.4 Hz, C3-H), 6.85 (1H, dd, J = 2.4, 8.5 Hz, Cg-H), 7.12 (1H, d- J = 2.4 Hz, C4-H), 7.17 (1H, t, J = 2.4 Hz, C2-H), 7.26 (1H, d, J = 8.5 Hz, C7-H), 8.03 (1H, s, NH). To a solution of 200 mg (0.79 mmol) of compound 79 in 3 ml of acetonitrile was added 118.1 g (0.79 mmol, 1.5 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 130.6 mg (0.94 mmol, 1.2 molar equivalent) of potassium carbonate and the mixture was stirred resulting with heating at an external temperature of 40 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 265.1 mg (82.8%) of a colorless oil 80. MS m / z: 324 (M +). NMR with H d: 1.38 (3H, d, J = 6.7 Hz, CH3), 2.01 (1H, dt, J = 6.7, 12.8 Hz, CH2), 2.67 (1H, dt, J = 6.7, 11.6 Hz, CH2) , 2.74 (1H, dt, J = 6.7, 13.4 Hz, CH2), 3.78 (1H, c, J = 6.7 Hz, CH), 3.81 (3H, s, 0CH3), 4.02-4.09 (2H, m, CH2) , 6.47 (1H, t, J = 3.1 Hz, C3 and -H), 6.78 (1H, dd, J = 3.1, 7.9 Hz, Cg-H), 6. 83 (1H, dd, J = 2.4, 8.5 Hz, Cg '-H), 6.90 (1H, d, J = 3.1 Hz, C2-H), 6.91 (1H, d, J = 7.9 Hz, C4-H) , 7.09 (1H, d, J = 2.4 Hz, C4 '- H), 7.18 (1H, t, J = 3.1 Hz, C2' -H), 7.23 (1H, t, J = 7.9 Hz, C5-H) , 7.27 ((1H, d, J = 8.5 Hz, C7 '-H), 8.07 (1H, s, NH).

EXAMPLE 34 SYNTHESIS OF THE COMPOUND 83 To a solution of 400 mg (2.35 mmol) of 4-phenylphenol 8.1 in 5 ml of acetonitrile, 0.48 ml (d = 1989, 4.7 mmoles, 2.0 molar equivalents) of 1,3-dibromopropane and 389.7 mg (2.82 mmoles, 1.2 molar equivalents) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C, for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 564.9 mg (82.5%) of colorless prismatic crystals 82. To a 300 mg solution (1.03 mmol) of compound 82. in 4 ml of acetonitrile was added 309.3 g (2.06 mmol, 2.0 molar equivalent) of (R) -3-methoxy-a-methylbenzylamine and 284.9 mg (2.06 mmol, 2.0 equivalents) molars) of potassium carbonate and the resulting mixture was stirred with heating at an external temperature of 60 ° C for 4 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by column chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 311.9 mg (83.8%) of colorless prismatic crystals 83. MS m / z: 361 (M +). NMR with H d: 1.36 (3H, d, J = 6.7 Hz, CH3), 1.93-2.01 (1H, m, CH2), 2.65 (1H, dt, J = 6.7, 11.6 Hz, CH2), 2.73 (1H, dt, J = 6.7, 11.6 Hz, CH2), 3.77 (1H, c, J = 6.7 Hz, CH), 3.80 (3H, s, OCH3), 4.02-4.10 (2H, m, CH2), 6.79 (1H, dd, J = 1.8, 7.3 Hz, Cg-H), 6.90 (1H, d, J = 1.8 Hz, C2-H), 6.91 (1H, d, J = 7.3 Hz, C4-H), 6.95 ( 2H, dt, J = 2.4, 9.2 Hz, C3 '-H), 7.24 (1H, t, J = 7.3 Hz, C5-H), 7.30 (1H, t, J = 7.3 Hz, C "-H), 7.42 (2H, t, J = 7.3 Hz, C3", 5" -H), 7.51 (2H, dd, J = 1.2, 7.3 Hz, C2 ', g'-H).

EXAMPLE 35 SYNTHESIS OF THE COMPOUND 88 To a solution of 600 mg (4.0 mmol) of (R) -3-methoxy-a-methylbenzylamine 84 in 5 ml of methylene chloride was added 662.4 mg (d = 1176, 4.4 mmol, 1.1 molar equivalents) of ethylmalonyl chloride and 0.66 ml (d = 0.726, 4.8 mmol, 1.2 molar equivalents) of triethylamine and the resulting mixture was stirred with heating at room temperature for 2 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with methylene chloride. The methylene chloride layer was washed with 5% aqueous solution of hydrochloric acid, with water and with saturated aqueous sodium chloride solution and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by chromatography (silica gel, ethyl acetate-n-hexane) to thereby give 790.0 mg (98.4%) of colorless prismatic crystals 85. NMR with 1H d: 1.21 (3H, t, J = 6.7 Hz, CH2CH3), 1.42 (3H, d, J = 6.7 Hz, CH3) 3.23 (2H, d, J = 4.3 Hz, CH2), 3.73 (3H, s, OCH3), 4.12 (2H, c, J = 6.7 Hz, CH2CH3), 5.04 (1H, dt, J = 6.7, 14.0 Hz, CH), 6.72 (1H, dd, J = 1.8, 7.9 Hz, Cg-H) , 6.79 (1H, d, J = 1.8, Hz, C2-H), 6.83 (1H, d, J = 7.9 Hz, C4-H), 7.18 (1H, t, J = 7.9 Hz, C5-H), 7.36 (1H, s, NH). To a solution of 897.6 mg (3.39 mmol) of compound 85 in 5 ml of ethanol was added 2 ml of a 10% aqueous solution of sodium hydroxide and the resulting mixture was stirred with heating at an external temperature of 80 ° C during 1 hour. After the reaction was complete, the reaction mixture was concentrated and acidified with 5% aqueous hydrochloric acid solution. The reaction mixture was then poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with a 5% aqueous solution of hydrochloric acid, with water and with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 790.0 mg (98.4%) of colorless prismatic crystals 86. NMR with 1H d: 1.47 (3H, d, J = 6.7 Hz, CH3), 3.27 (2H, d, J = 9.2 Hz, CH2), 3.77 (3H, s, OCH3), 5.05 (1H, dt, J = 6.7, 14.0 Hz, CH), 6.78 (1H, dd, J = 2.4, 7.9 Hz, Cg-H), 6.83 (1H, d, J = 2.4, Hz, C2-H), 6.86 (1H, d, J = 7.9 Hz, C4-H), 7.23 (1H, t, J = 7.9 Hz, C5-H), 7.47 (1H, d, J = 7.9 Hz, NH). To a solution of 400 mg (1.68 mmol) of the compound 86 in 5 ml of dimethylformamide, 278.5 mg (1.86 mmoles, 1.1 molar equivalents) of (R) -3-methoxy-a-methylbenzylamine and 389.5 mg (2.02 mmoles, 1.2 molar equivalents) of WSCxHCl were added and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 615.4 mg (98.5%) of colorless prismatic crystals 87. NMR with 1H d: 1.42 (6H, d, J = 6.7 Hz, CH3), 3.15 (2H, s, CH2), 3.75 (6H, s, OCH3), 5.04 (2H, dt, J = 7.9, 14.7 Hz, CH), 6.77 (2H, dd, J = 2.4, 7.9 Hz, C6 / 6'-H), 6.80 (2H, d, J = 2.4, Hz, C2 (2'-H) - 6-83 (2H, d, J = 7.9 Hz, C4f4.-H), 7.20 (2H, t, J = 7.9 Hz, C5 / 5'-H), 7.47 (2H, s, NH). To a solution of 100 mg (0.270 mmol) ) of compound 87 in 5 ml of absolute tetrahydrofuran was added 0.59 ml (0.59 mmoles, 1.2 molar equivalents) of a 1 molar solution of boron trihydride in tetrahydrofuran.The resulting mixture was warmed to room temperature and then stirred for 3 hours After the reaction was completed, the reaction mixture was poured into water, acidified with a 5% aqueous solution of acid hydrochloric acid and then extracted with ethyl acetate. The hydrochloric acid layer was made alkaline by adding a 5% aqueous solution of sodium hydroxide and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 76.3 mg (82.6%) of a colorless oil 8.8 MS m / z: 342 (M +). NMR with 1H d: 1.43 (6H, d, J = 6.7 Hz, CH3), 1. 62 (2H, dt, J = 6.7, 13.4 Hz, CH2), 2.46 (2H, dt, J = 6.7, 13.4 Hz, CH2), 2.54 (2H, dt, J = 6.7, 11.6 Hz, CH2), 3.75 (2H, c, J = 6.7 Hz, CH), 3.80 (6H, s, OCH3), 6.77 (2H, dd, J = 2.4, 7.3 Hz, Cg / 6'-H), 6.86 (2H, d, J = 2.4, Hz, C2, 2'H), 6.87 (2H, d, J = 7.3 Hz, C4 / 4.-H), 7.23 (2H , t, J = 7.3 Hz, C5 / 5'-H).

EXAMPLE 36 SYNTHESIS OF THE COMPOUND 93 To a solution of 600 mg (3.5 mmol) of (R) -1- (1-naphthyl) ethylamine 89 in 5 ml of methylene chloride was added 580.3 mg (d = 1176, 3.85 mmol, 1.1 molar equivalent) of sodium chloride. ethyl malonyl and 0.59 ml (d = 0.726, 4.2 mmol, 1.2 molar equivalents) of triethylamine and the resulting mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with methylene chloride. The methylene chloride layer was washed with 5% aqueous solution of hydrochloric acid, with water and with saturated aqueous sodium chloride solution and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 662.9 mg (66.5%) of colorless prismatic crystals 90. NMR with H d: 1.16 (3H, t, J = 7.3 Hz, CH2CH3), 1.60 (3H, d, J = 7.3 Hz, CH3) 3.24 (2H, dd, J = 17.7, 26.3 Hz, CH2), 4.07 (2H, c, J = 7.3 Hz, CH2CH3), 5.89 (1H, dt, J = 7.3, 14.6 Hz, CH), 7.35 (1H, d, J = 7.9 Hz, NH ), 7.38 (1H, t, J = 7.9 Hz, C3-H), 7.44 (1H, t, J = 12.2 Hz, Cg-H), 7.45 (1H, d, J = 7.9 Hz, C2-H), 7.46 (1H, t, J = 12.2 Hz, C7-H), 7.72 (1H, d, J = 7.9 Hz, C4-H), 7.79 (1H, d, J = 7.9 Hz, C5-H), 8.03 ( 1H, d, J = 7.9 Hz, C8-H). To a solution of 662.5 mg (2.32 mmol) of compound 90 in 5 ml of ethanol was added 2 ml of a 10% aqueous solution of sodium hydroxide and the resulting mixture was stirred with heating at an external temperature of 80 ° C during 1 hour. After the reaction was complete, the reaction mixture was concentrated and acidified with 5% aqueous hydrochloric acid solution. The reaction mixture was then poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with a 5% aqueous solution of hydrochloric acid, with water and with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 596.0 mg (99.8%) of colorless prismatic crystals 91. NMR with H d: 1.66 (3H, d, J = 6.7 Hz, CH3), 3.20 (2H, dd, J = 18.3, 29.9 Hz, CH2), 5.91 (1H, dt, J = 6.7, 14.7 Hz, CH) , 6.99 (1H, d, J = 7.3 Hz, NH), 7.43 (1H, t, J = 7.9, Hz, C3-H), 7.48 (1H, t, J = 7.9 Hz, Cg-H), 7.49 ( 1H, d, J = 7.9 Hz, C2-H), 7.53 (1H, dt, J = 1.2, 7.9 Hz, C7-H), 7.77 (1H, d, J = 7.9, Hz, C4-H), 7.83 (1H, t, J = 7.9, Hz, C5-H), 8.00 (1H, d, J = 7.9, Hz, C8-H). To a solution of 400 mg (1.56 mmoles) of compound 91 in 5 ml of dimethylformamide was added 293.2 mg (1.71 mmoles, 1.1 molar equivalents) of (R) -1- (1-naphthyl) ethylamine and 359.2 mg (1.87 mmoles). , 1.2 molar equivalents) of WSCxHCl and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals obtained were purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 615.1 mg (96.4%) of colorless prismatic crystals 92. To a solution of 100 mg (0.24 mmoles) of compound 92. in 5 ml of absolute tetrahydrofuran was added 0.54 ml (0.54 mmoles, 2.2 molar equivalents) of a 1 molar solution of boron trihydride in tetrahydrofuran. The resulting mixture was heated to room temperature and then stirred for 3 hours. After the reaction was complete, the reaction mixture was poured into water, acidified with a 5% aqueous solution of hydrochloric acid and then extracted with ethyl acetate. The hydrochloric acid layer was made alkaline by adding a 5% aqueous solution of sodium hydroxide and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography (silica gel, n-hexane-ethyl acetate) to thereby give 82.0 mg (88.0%) of a colorless oil 93. MS m / z: 382 (M +). NMR with 1H d: 1.47 (6H, d, J = 6.7 Hz, CH3), 1.72 (2H, dt, J = 6.7, 13.4 Hz, CH2), 2.62 (2H, dt, J = 6.7, 13.4 Hz, CH2) , 2.68 (2H, dt, J = 6.7, 11.6 Hz, CH2), 4.60 (2H, c, J = 6.7 Hz, CH), 7.45 (2H, t, J = 7.9 Hz, C3 / 3'-H), 7.48 (2H, dt, J = 1.8, 7.9, Hz, Cg / 6'-H), 7.50 (2H, t, J = 7.9 Hz, C7 7? -H), 7.60 (2H, d, J = 7.9 Hz , C2 / 2'-H), 7.74 (2H, t, J = 7.9 Hz, C4í4.-H), 7.87 (2H, dd, J = 1.8, 7.9 Hz, C5 / 5.-H), 8.16 (2H , d, J = 7.9 Hz, c8, 8 '~ H) • EXAMPLE 37 SYNTHESIS OF THE COMPOUND 103 Compound 102 To a solution of 300 mg (1.26 mmol, of 6-hydroxyflavone 101 in 5 ml of acetonitrile, 0.26 ml (d = 1989, 2.52 mmol, 2.0 molar equivalents) of 1,3-dibromopropane and 208.8 mg (1.51 mmol) were added. mmoles, 1.2 molar equivalents) of potassium carbonate, and the resulting mixture was stirred under heating at an external temperature of 60 ° C. for 4 hours.After the reaction was completed, the reaction mixture was poured into water and extracted with acetate The ethyl acetate layer was washed with water and with saturated aqueous sodium chloride solution, After drying over sodium sulfate, the solvent was distilled off under reduced pressure, The residue thus obtained was purified by column chromatography. [silica gel, ethyl acetate / n-hexane] to thereby give 361.8 mg (80.0%) of compound 102 as colorless prisms MS m / z: 375 (M +). RMN with 1H £: 2.34-2.39 (2H, m, CH2), 3.62 (2H, t, J = 6.7 Hz, CH2), 4.22 (2H, t, J = 6.7 CH2), 6.82 (1H, s, Ar-H), 7.29 (1H, dd, J = 3.1, 9.2 Hz, Ar-H), 7.51 (4H, m, Ar-H), 7.61 (1H, d, J = 3.1 Hz, Ar-H), 7.92 (1H, dd, J = 1.8, 7.9 Hz, Ar-H), 7.19 (1H, dd, J = 3.1, 9.2 Hz, Ar-H), 7.44- 7.53 (7H, m, Ar-H), 7.57 (1H, d, J = 3.1 Hz, Ar-H), 7.68 (1H, d, J = 7.3 Hz, Ar-H), 7.74 (1H, d, J = 7.9 Hz, Ar-H), 7.86 (1H, d, J = 7.9 Hz, Ar-H), 7.91-7.93 (2H, m, Ar-H), 8.19 (1H, d, J = 8.5 Hz, Ar -H), Compound 103 To a solution of the above compound 102 (125.8 mg, 0.38 mmol, 1.2 molar equivalents) in 3 ml of acetonitrile, 50 mg (0.29 mmol) of (R) - (+) -1- ( 1-naphthyl) ethylamine and 60.5 mg (0.44 mmol, 1.5 molar equivalents) of potassium carbonate, and the resulting mixture was stirred with heating at an outside temperature of 40 ° C, for 6 hours. After the reaction was completed, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The residue thus obtained was purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 67.1 mg (89.5%) of compound 103 as a colorless oil. MS m / z: 449 (M +). NMR with 1H d: 1.55 (3H, d, J = 6.7 Hz, CH3), 2.04 (2H, t, J = 6. 1 Hz, CH2), 2.07 (1H, s, NH), 4.15 (1H, t, J = 6.1 Hz, CH2), 4.71 (1H, c, J = 6.7 Hz, CH), 6.82 (1H, s, Ar-H), 7.19 (1H, dd, J = 3.1, 9.2 Hz, Ar-H) , 7.44-7.53 (7H, m, Ar-H), 7.57 (1H, d, J = 3.1 Hz, Ar-H), 7.68 (1H, d, J = 7.3 Hz, Ar-H), 7.74 (1H, d, J = 7.9 Hz, Ar-H), 7.86 (1H, d, J = 7.9 Hz, Ar-H), 7.91-7.93 (2H, m, Ar-H), 8.19 (1H, d, J = 8.5 Hz, Ar-H), EXAMPLE 38 S NTESIS OF THE COMPOUND 106 Compound 105 To a solution of 500 mg (2.74 mmoles) of 9-hydroxyfluorene 104, in 5 ml of toluene, 0.273 ml (d = 1.537, 3.02 mmoles, 1.1 molar equivalents) of 3 - bromo-1-propane and 5.1 mg (0.027 mmol, 0.01 molar equivalents) of p-toluenesulfonic acid hydrate, and the resulting mixture was stirred at room temperature for 1 hour. After the reaction was complete, the resulting mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The residue obtained was purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 723.4 mg (87.0%) of compound 105, as a colorless oil Compound 106 to a solution of compound 105 above (106.2 mg, 0.35 mmol, 1.2 molar equivalents) in 3 ml of acetonitrile, was added 50 mg (0.29 mmol) of (R) - (+) -1- (1-naphthyl) ethylamine and 48.4 mg (0.35 mmol, 1.2 molar equivalents) of potassium carbonate, and the resulting mixture was stirred with heating at an outside temperature of 60 ° C, for 6 hours. After the reaction is completedThe reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The residue thus obtained was purified by column chromatography [silica gel, ethyl acetate / n-hexane] to give 33.7 mg (76.1%) of the compound 106 as a colorless oil. MS m / z: 393 (M +). NMR with ^ -HS: 1.47 (3H, d, J = 6.1 Hz, CH3), 1.70-1.76 (2H, m, CH2), 2.60-2.71 (2H, m, CH2), 3.26 (2H, t, J = 6.1 Hz, CH2), 4.61 (1H, c, J = 6.7 Hz, CH), 5.59 (1H, s, CH), 7.26 (1H, d, J = 7.3 Hz, Ar-H), 7.28 (1H, t, J = 7.3 Hz, Ar-H), 7.37 (1H, d, J = 7.3 Hz, Ar-H), 7.38 (1H, t, J = 7.3 Hz, Ar-H), 7.46 (1H, t, J = 7.3 Hz, Ar-H), 7.48 (1H, t, J = 7.3 Hz, Ar-H), 7.49 (1H , t, J = 7.9 Hz, Ar-H), 7.53 (1H, d, J = 7.3 Hz, Ar-H), 7.54 (1H, d, J = 7.3 Hz, Ar-H), 7.63 (1H, d , J = 6.7 Hz, Ar-H), 7.66 (2H, d, J = 7.9 Hz, Ar-H), 7.75 (1H, d, J = 8.5 Hz, Ar-H), 7.88 (1H, d, J = 7.9 Hz, Ar-H), 8.20 (1H, d, J = 8.5 Hz, Ar-H).

EXAMPLE 39 SYNTHESIS OF THE COMPOUND 109 Compound 108 To a solution of 500 mg (2.71 mmol) of 2-hydroxybenzofuran 107, in 5 ml of acetonitrile, 0.55 ml (d = 1989, 5.43 mmol, 2.0 molar equivalent) of 1 was added. 3-dibromopropane and 750.1 mg (5.43 mmoles, 1.0 molar equivalents) of potassium carbonate, and the resulting mixture was stirred at an outside temperature of 60 ° C for 4 hours. After the reaction was complete, the resulting mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 804.3 mg (77.0%) of compound 108, as colorless prisms. Compound 109 To a solution of compound 108 above (106.9 mg, 0.35 mmol, 1.2 molar equivalent) in 3 ml of acetonitrile, 50 mg (0.29 mmol) of (R) - (+) -1- (1-naphthyl) was added. ethylamine and 60.5 mg (0.44 mmol, 1.5 molar equivalents) of potassium carbonate, and the resulting mixture was stirred with heating at an outside temperature of 60 ° C, for 6 hours. After the reaction was completed, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The residue thus obtained was purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 67.2 mg (58.3%) of compound 109 as a colorless oil. MS m / z: 395 (M +). NMR with 1H Ü: 1.53 (3H, d, J = 6.7 Hz, CH3), 2.02-2.07 (2H, m, CH2), 2.78-2.89 (2H, m, CH2), 4.13-4.16 (2H, m, CH2 ), 4.69 (1H, c, J = 6.7 Hz, CH), 7.00 (1H, dd, J = 2.4, 8.6 Hz, Ar-H), 7.33 (1H, t, J = 7.3 Hz, Ar-H), 7.38 (1H, d, J = 2.4 Hz, Ar-H), 7.44-7.51 (6H, m, Ar-H), 7.67 (1H, d, J = 7.3 Hz, Ar-H), 7.75 (1H, d , J = 7.3 Hz, Ar-H), 7.87 (1H, dd, J = 2.4, 9.7 Hz, Ar-H), 7.89 (1H, d, J = 7.9 Hz, Ar-H), 8.22 (1H, d , J = 8.6 Hz, Ar-H).

EXAMPLE 40 SYNTHESIS OF THE COMPOUND 112 Compound 111 To a solution of 500 mg (3.76 mmol) of 5-hydroxyindole 110, in 5 ml of acetonitrile, 833.9 mg was added. (d = 1989, 4.13 mmoles, 1.1 molar equivalents) of 1,3-dibromopropane and 570.9 mg (4.13 mmoles, 1.1 molar equivalents) of potassium carbonate, and the resulting mixture was stirred at an outside temperature of 60 ° C for 4 hours. hours. After the reaction was complete, the resulting mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The obtained residue was purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 586 mg (61.4%) of compound 111, as a colorless oil. NMR with 1H: 1.70 (3H, d, J = 6.7 Hz, CH2), 3.63 (2H, t, J = 6.7 Hz, CH2), 4.13 (2H, t, J = 6.7 CH2), 6.47 (1H, t, J = 2.4 Hz, Ar-H), 6.85 (1H, dd, J = 2.4, 9.2 Hz, Ar-H), 7.12 (1H, d, J = 2.4 Hz, Ar-H), 7.17 (1H, t, J = 2.4 Hz, Ar-H), 7.26 (1H, d, J = 8.5 Hz, Ar-H), 8.03 (1H, s, NH). Compound 112 To a solution of compound 111 above (65.3 mg, 0.26 mmol, 1.5 molar equivalents) in 3 ml of acetonitrile, 29.3 mg (0.17 mmol) of (R) - (+) -1- (1-naphthyl) was added. ethylamine and 35.5 mg (0.26 mmol, 1.5 molar equivalents) of potassium carbonate, and the resulting mixture was stirred with heating at an outside temperature of 60 ° C, for 6 hours. After the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The ethyl acetate layer and saturated aqueous sodium chloride solution were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The residue thus obtained was purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 36.5 mg (62.0%) of compound 112 as a colorless oil. MS m / z: 344 (M +). NMR with HQ: 1.52 (3H, d, J = 6.1 Hz, CH3), 1.99-2.04 (2H, m, CH2), 2.76-2.86 (2H, m, CH2), 4.05-4.12 (2H, m, CH2) , 4.67 (1H, c, J = 6.1 Hz, CH), 6.47 (1H, S, Ar-H), 6.83 (1H, dd, J = 2.4, 8.6 Hz, Ar-H), 7.09 (1H, d, J = 2.4 Hz, Ar-H), 7. 17 (1H, t, J = 2.4 Hz, Ar-H), 7.26 (1H, d, J = 9.2 Hz, Ar-H), 7.44-7.50 (3H, m, Ar-H), 7.67 (1H, d , J = 7.3 Hz, Ar-H), 7.74 (1H, d, J = 8.5 Hz, Ar-H), 7.87 (1H, dd, J = 2.4, 6.7 Hz, Ar-H), 8. 10 (1H, s, NH), 8.20 (1H, d, J = 7.9 Hz, Ar-H).

EXAMPLE 41 SYNTHESIS OF THE COMPOUND 117 Compound 114 To a solution of 600 mg (3.5 mmol) of (R) - (+) -1- (1-naphthyl) ethylamine in 5 ml of dichloromethane was added 580.3 mg (3.85 mmol, 1.1 molar equivalent) of sodium chloride. ethylmalonyl 113 and 0.59 ml (d = 0.726, 3.85 mmol, 1.1 molar equivalents) of triethylamine, and the resulting mixture was stirred at room temperature for 2 hours. After completion of the reaction, the reaction mixture was poured into water and extracted with dichloromethane. The dichloromethane layer was washed successively with a 5% aqueous solution of hydrochloric acid, with water and with a saturated aqueous solution of sodium chloride. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The crystals thus obtained were purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 662.9 mg (66.5%) of compound 114, as colorless prisms. NMR with ^ S: 1.16 (3H, t, J = 7.3 Hz, CH2CH3), 1.60 (3H, d, J = 7.3 CH3), 3.24 (2H, dd, J = 17.7, 26.3 Hz, CH2), 4.07 (2H , c, J = 7.3 CH2CH3), 5.89 (1H, dt, J = 7.3, 14.6 Hz, CH), 7.35 (1H, d, J = 7.9 Hz, NH), 7.38 (1H, t, J = 7.9 Hz, Ar-H), 7.44 (1H, t, J = 12.2 Hz, Ar-H), 7.46 (1H, t, J = 12.2 Hz, Ar-H), 7.72 (1H, d, J = 7.9 Hz, Ar- H), 7.79 (1H, d, J = 7.9 Hz, Ar-H), 8.03 (1H, d, J = 7.9 Hz, Ar-H). Compound 115 To a solution of 662.5 mg (2.32 mmol) of compound 114 above in 5 ml of ethanol, 1 ml of a 10% aqueous solution of sodium hydroxide was added, and the resulting mixture was stirred with heating at an external temperature. of 80 ° C, for 1 hour. After the reaction was complete, the reaction mixture was concentrated, acidified with a 5% aqueous solution of hydrochloric acid, poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed successively with 5% aqueous hydrochloric acid solution, with water and with saturated aqueous sodium chloride solution. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The crystals thus obtained were purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 659.5 mg of compound 115, as colorless prisms.

NMR with HS: 1.66 (3H, d, J = 6.7 Hz, CH3), 3.20 (2H, dd, J = 18.3, 29.9 CH2), 5.91 (1H, dt, J = 6.7, 14.7 Hz, CH), 6.99 ( 1H, d, J = 7.3 Hz, NH), 7.43 (1H, t, J = 7.9 Hz, Ar-H), 7.48 (1H, d, J = 7.9 Hz, Ar-H), 7.53 (1H, dt, J = 1.2, 6.7 Hz, Ar-H), 7.77 (1H, 5 d, J = 8.5 Hz, Ar-H), 7.83 (1H, d, J = 7.9 Hz, Ar-H), 8.00 (1H, d , J = 8.5 Hz, Ar-H). Compound 116 To a solution of 50 mg (0.19 mmol) of the above compound 115 in 3 ml of N, N-dimethylformamide was added 45.0 mg (0.21 mmol, 1.1 molar equivalents) of (R) - (+) -1- (1-B | naphthyl) ethylamine and 44.9 mg (0.23 mmol, 1.2 molar equivalents) of WSCHCl and the resulting mixture was stirred at the temperature environment for 1 hour. After the reaction was completed, it was poured into Water was added to the reaction mixture and extracted with ethyl acetate.

The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water. After drying over sodium sulphate, the solvent was distilled off under reduced pressure. The crystals thus obtained were purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 61.6 mg (70.5%) of compound 116, as colorless prisms. NMR with H? . : 1.43 (3H, d, J = 6.7 Hz, CH2CH3), 1.72 (3H, d, J = 6.7 Hz, CH3), 3.38 (2H, d, J = 2.5 Hz, CH2), 4.36 (23H, c, J = 6.7 Hz, CH2CH3), 5.32-6.01 (1H, m, CH), 6.88 (1H, d, J = 9.2 Hz, Ar-H), 7.21 (1H, t, J = 6.7 Hz, Ar-H), 7.33 (1H, d, J = 8.6 Hz, Ar-H), 7.40 (1H, d, J = 7.9 Hz, Ar-H), 7.44-7.56 (5H, m, Ar-H) 7.80 (1H, d , J = 7.9 Hz, Ar-H), 7.88 (1H, d, J = 9.2 Hz, Ar-H), 8.06 (1H, d, J = 7.9 Hz, Ar-H), 8.11 (1H, d, J = 8.5 Hz, Ar-H), 8.29 (1H, d, J = 1.8 Hz, Ar-H). Compound 117 To a solution of 50 mg (0.11 mol) of the above compound 116 in 3 ml of tetrahydrofuran, 0.24 ml (0.24 mmol, 2.2 molar equivalent) of a 1 molar solution of borane-tetrahydrofuran was added, while cooling with ice. Then the temperature was raised to room temperature and the mixture was stirred for 6 hours. After the reaction was completed, water was poured into the reaction mixture. The mixture was then acidified with a 5% aqueous solution of hydrochloric acid and extracted with ethyl acetate. The layer of the 5% aqueous solution of hydrochloric acid was made alkaline by adding a 5% aqueous solution. % sodium hydroxide, and then extracted with ethyl acetate. After washing with water and with an aqueous solution of sodium chloride and drying over sodium sulfate, the solvent was distilled off under reduced pressure. The crystals thus obtained were purified by column chromatography [silica gel, ethyl acetate / n-hexane] to thereby give 18.0 mg (88.0%) of compound 117, as a colorless oil. MS m / z: 421 (M +). NMR with xH? : 1.38 (3H, d, J = 7.3 Hz, CH2CH3), 1.56 (3H, d, J = 6.7 Hz, CH3) 1.90 (2H, m, CH2), 2.75 (2H, m, CH2), 2.81 (2H, m, CH2), 3.29 (2H, t, J = 6.7 Hz, CH2), 4.29 (2H, c, J = 7.3 Hz, CH2CH3), 4.79 (1H, c, J06.1 Hz, CH), 6.81 (1H , dd, J = 1.8, 8.6 Hz, Ar-H), 7.13 (1H, t, J = 7.3 Hz, Ar-H), 7.20 (1H, d, J = 8.6 Hz, Ar-H), 7.27 (1H , d, J = 1.8 Hz, Ar-H), 7.32 (1H, d, J = 7.9 Hz, Ar-H), 7.39 (1H, t, J = 7.3 Hz, Ar-H), 7.46 (3H, m , Ar-H), 7.65 (1H, d, J = 10.4 Hz, Ar-H), 7.75 (1H, d, J = 8.6 Hz, Ar-H), 7.86 (1H, dd, J = 2.4, 6.7 Hz , Ar-H), 7.98 (1H, d, J = 7.3 Hz, Ar-H), 8.16 (1H, d, J = 8.6 Hz, Ar-H).

EXAMPLE 42 COMPOUND S NTESIS 123 Compound 119 9.7 g of 2-methoxycarbonyl thiophenol 118 was dissolved in 200 ml of N, N-dimethylformamide and 2.7 g of 60% sodium hydride was added at 0 ° C. When foam formation ceased, added 20.0 g of (±) -2-tert-butoxycarbonylamino-1-methanesulfonyloxy-2-phenylethane, and the resulting mixture was stirred at room temperature for 12 hours. P After the reaction was completed, excess ammonium chloride was added and the reaction mixture was extracted with ethyl acetate. The extract was washed with an aqueous solution of sodium chloride and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the crystals thus obtained were purified by column chromatography [silica gel, ethyl acetate / n-hexane) to give that way 16.0 g of compound 119. Compound 120 1.9 g of the above compound 119 was dissolved in diphenylether and 100 mg of p-toluenesulfonic acid hydrate was added thereto. The resulting mixture was heated at 250-260 ° C for 40 minutes. After cooling allowing it to stand, it was purified by column chromatography and eluted with ethyl acetate / n-hexane to thereby give 700 mg of compound 120. Compound 121 150 g of the above compound 120 was dissolved in tetrahydrofuran and he added 310 mg of lithium aluminum hydride. The resulting mixture was then heated at reflux for 5 hours. After the reaction was complete, excess sodium sulfate decahydrate was added and the mixture was filtered through Celite. The filtrate was concentrated and 330 mg of compound 121. was obtained. Compound 122 3.0 g of the above compound 121 and 1.5 g of triethylamine in tetrahydrofuran were dissolved and 1.2 g of acryloyl chloride was added while cooling with ice . After stirring the mixture at room temperature for 30 minutes, a saturated aqueous solution of sodium bicarbo was added thereto, and then it was extracted with chloroform. The extract was washed with a saturated aqueous solution of sodium chloride and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the obtained residue was purified by column chromatography [silica gel / n-hexane] to thereby give 1.5 g of compound 122. Compound 123 5 150 mg (0.51 mmol) was dissolved of compound 122 and 104. 5 mg (0.61 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in 3 ml of chloroform / methanol, and then allowed to stand at room temperature for one week. After the reaction was completed it was removed by distillation the solvent under reduced pressure. The ^ p oil thus obtained by column chromatography [silica gel, chloroform / methanol] to thereby give 167.4 mg (70.7%) of compound 123, as a colorless oil. MS m / z: 466 (M +). NMR with ^ S: 1.46 (3H, C, J = 6.7 Hz, CH3), 2.33-2.36 (1H, m, CH2), 2.79-2.93 (3H,, CH2), 3.25-3.38 (1H, m, CH2), 3.57-3.65 (1H, m, CH2), 4.41-4.45 (1H, m, CH2), 4.56-4.65 (1H, m, CH2), 6.30-6.34 (1H, m, CH), 7.17 (3H, m, Ar-H), f 7.27-7.51 (9H, m Ar-H) , 7.63 (1H, t, J = 4.9 Hz, Ar-H), 7.73 (1H, t, J = 8.5 Hz, Ar-H), 7.84-7.87 (1H, m Ar-H), 8.11-8.19 (1H , m Ar-H).

EXAMPLE 43 SYNTHESIS OF K-2003 520 mg (3.01 mmol) of 4-bromophenol was dissolved in 11 ml of acetonitrile and then 1,243 g (8.99 mmoles) of potassium carbo and 0.37 ml (3.64 mmoles) of 1,3-dibromopropane were added in succession at room temperature. The resulting mixture was stirred by heating under reflux at 95 ° C for 4 hours. After confirming that the reaction was complete by TLC, 800 mg (5.79 mmoles) of potassium carbo and 450 mg (2.98 mmoles) of (R) - (+) - 3-methoxy- < C-methylbenzylamine, at room temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 18 hours. After After completing the reaction, the reaction was cooled by letting it stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1) to thereby give 364 mg (1.00 mmol) of compound K-2003, like a pale yellow syrup, with a yield of 33%. NMR at 500 MHz 7.22 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 7.34 (2H, dd, J = 8.3 Hz, J = 8.3 Hz), 6.87-6.88 (1H, m), 6.87 (1H , s), 6.76-6.78 (1H, m), 6.74 (2H, dd, J = 8.3 Hz, J = 2.0 Hz), 3.93-4.00 (2H, m), 3.79 (3H, s), 3.74 (1H, c, J = 6.5 Hz), 2.58-2.71 (2H, m), 1.88-1.95 (2H, m), 1.53 (1H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 363 , 365 EXAMPLE 44 SYNTHESIS OF K-2004 570 mg (3.29 mmol) of 4-bromophenol was dissolved in 11 ml of acetonitrile and then 1.08 g was successively added. (7.81 mmoles) of potassium carbonate and 0.44 ml (3.68 mmoles) of 1,4-dibromobutane, at room temperature. The resulting mixture was stirred by heating under reflux at 95 ° C for 4 hours. After confirming that the reaction was complete by TLC, 455 mg (3.29 mmol) of potassium carbonate and 400 mg (2.64 mmol) of (R) - (+) - 3-methoxy-O-methylbenzylamine were added to the room temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 18 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1) to thereby give 422 mg (1.11 mmol) of compound K-2004, as a pale yellow syrup, in a yield of 43%. %. NMR at 500 MHz 7.34 (2H, d, J = 9.0 Hz), 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 6.77-6.88 (3H, m), 6.73 (2H, d,, J = 6.5 Hz), 3.86 (2H, t, J = 6.5 Hz), 3.80 (3H, s), 3.72 (1H, c, J = 7.0 Hz), 2.46-2.59 (2H, m), 1.73-1.83 (2H , m), 1.56-1.67 (2H, m), 1.51 (1H, s), 1.34 (3H, d, J = 7.0 Hz), m / z = 377, 379.

EXAMPLE 45 SYNTHESIS OF K-2005 710 mg (4.10 mmol) of 4-bromophenol was dissolved in 11 ml of acetonitrile and then 710 mg (5.14 mmol) of potassium carbonate and 0.44 ml (4.55 mmol) of 1,5-dibromopentane were successively added at the temperature ambient. The resulting mixture was stirred by heating under reflux at 95 ° C for 4 hours. After confirming that the reaction was complete by TLC, 455 mg (3.29 mmol) of potassium carbonate and 370 mg (2.45 mmol) of (R) - (+) - 3-methoxy-methyl-benzylamine were added at the temperature environment, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1) to thereby give 295 mg (0.75 mmol) of compound K-2005, as a pale yellow syrup, with a yield of 30%. %. NMR at 500 MHz 7.34 (2H, d, J = 7.0 Hz), 7.23 (1H, dd, J = 8.5 Hz, J = 8.5 Hz), 6.87-6.89 (2H, m), 6.77 (1H, dd, J = 8.5 Hz, J = 1.5 Hz), 6.74 (2H, d, J = 8.5 Hz), 3.88 (2H, t, J = 6.3 Hz), 3.80 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.36-2.55 (4H, m), 1.55-1.77 (2H, m), 1.43-1.57 (2H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 391, 393 .

EXAMPLE 46 SYNTHESIS OF K-2006 500 mg (2.89 mmol) of 4-bromophenol was dissolved in 10 ml of acetonitrile and then 540 mg was successively added (3.90 mmoles) of potassium carbonate and 0.49 ml (3.18 mmoles) of 1,6-dibromohexane, at room temperature. The resulting mixture was stirred by heating under reflux at 95 ° C for 4 hours. After confirming that the reaction was complete by TLC, 400 mg (2.89 mmol) of potassium carbonate and 270 mg (1.79 mmol) of (R) - (+) - 3-methoxy-methylbenzylamine were added to the ambient temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1) to thereby give 364 mg (0.896 mmol) of compound K-2006, like a pale yellow syrup, with a yield of 50%. NMR at 500 MHz 7.34 (2H, d, J = 8.0 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.88-6.89 (1H, m), 6.88 (1H, s), 6.78 (1H, dd, J = 8.0 Hz, J = 3.0 Hz), 6.75 (2H, d, J = 8.0 Hz), 3.88 (2H, t, J = 6.3 Hz), 3.81 (3H, S), 3.73 (1H , c, J = 7.0 Hz), 2.41-2.53 (2H, m), 1.71-1.77 (2H, m), 1.35-1.52 (7H, m), 1.34 (3H, d, J = 7.0 Hz), m / z = 405, 407.

EXAMPLE 47 SYNTHESIS OF K-2007 490 mg (2.83 mmol) of 4-bromophenol was dissolved in ml of acetonitrile and then 495 mg was added successively (3.58 mmoles) of potassium carbonate and 0.53 ml (3.10 mmoles) of 1,7-dibromoheptane, at room temperature. The resulting mixture was stirred by heating under reflux at 95 ° C for 4 hours. After confirming that the reaction was complete by TLC, 400 mg (2.89 mmol) of potassium carbonate and 300 mg (1.98 mmol) of (R) - (+) - 3-methoxy-O-methylbenzylamine were added to the ambient temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 24 hours. After the reaction was complete, the reaction was cooled by allowing it to stand at room temperature. After . After pouring water, the mixture was subjected to extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. Dried over sodium sulfate The organic layer thus obtained was anhydrous and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 100: 1) to thereby give 150 mg (0.36 mmol) of the compound K-2007, as a pale yellow syrup, with a yield of 18%. NMR at 500 MHz 7.34 (2H, d, J = 8.5 Hz), 7.24 (1H, dd, J = 7.8 Hz, J = 7.8 Hz), 6.90-6.93 (2H, m), 6.79 (1H, dd, J = 7.8 Hz, J = 1.8 f Hz), 6.75 (2H, d, J = 8.5 Hz), 3.88 (2H , t, J = 6.3 Hz), 3.82 (3H, s), 3.79-3.80 (1H, m), 2.43-2.54 (2H, m), 1.70-1.84 (2H, m), 1.20-1.56 (9H, m), 1.41 (3H, d, J = 6.5 Hz), m / z = 419, 421.

EXAMPLE 48 SYNTHESIS OF K-2010 615 mg (3.45 mmol) of 3- trifluoromethylthiophenol was dissolved in 12 ml of acetonitrile and then 467 mg (3.38 mmol) of potassium carbonate and 0.46 ml (3.85 mmol) of 1,4-dibromobutane were successively added thereto. room temperature. The resulting mixture was stirred at the same temperature for 5 hours. After confirming that the reaction was complete by TLC, 210 mg (1.52 mmoles) of potassium carbonate and 360 mg (2.38 mmoles) of (R) - (+) - 3-methoxy-C-methylbenzylamine were added to the room temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 18 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 180 mg (0.47 mmol) of compound K-2010, as a pale yellow syrup, with a yield of 20%. %. NMR at 500 MHz 7.51 (1H, s), 7.35-7.44 (3H, m), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.88 (2H, m), 6.76-6.78 ( 1H, m), 3.80 (1H, s), 3.71 (1H, c, J = 6.5 Hz), 2.93 (2H, t, J = 7.5 Hz), 2.50-2.55 (1H, m), 2.42-2.47 (1H , m), 1.55-1.71 (4H, m), 1.45 (1H, s), 1.33 (3H, d, J = 6.5 Hz), m / z = 383.

EXAMPLE 49 SYNTHESIS OF K-2011 600 mg (3.37 mmol) of 3-trifluoromethylthiophenol was dissolved in 12 ml of acetonitrile and then 540 mg (3.96 mmol) of potassium carbonate and 0.50 ml (3.67 mmol) of 1,5-dibromopentane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 5 hours. After confirming that the reaction was complete by TLC, 240 mg (1.74 mmoles) of potassium carbonate and 300 mg (1.98 mmoles) of (R) - (+) - 3-methoxy-cc-methylbenzylamine were added to the room temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 18 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 220 mg (0.55 mmol) of compound K-2011, like a pale yellow syrup, with a yield of 28%. NMR at 500 MHz 7.45-7.44 (1H, m), 7.35-7.40 (2H, m), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.88 (2H, m), 6.76- 6.79 (1H, m), 3.81 (1H, s), 3.71 (1H, c, J = 6.5 Hz), 2.93 (2H, t, J = 7.5 Hz), 2.47-2.51 (1H, m), 2.40-2.45 (1H, m), 1.61-1.67 (2H, m), 1.41-1.52 (5H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 397.

EXAMPLE 50 SYNTHESIS OF K-2012 515 mg (2.89 mmoles) of 3-trifluoromethylthiophenol were dissolved in 10 ml of acetonitrile and then 440 mg (3.18 mmoles) of potassium carbonate and 0.45 ml (2.93 mmoles) of 1,6-dibromohexane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 5 hours. After confirming that the reaction was complete by TLC, 270 mg (1.95 mmol) of potassium carbonate and 260 mg (1.72 mmol) of (R) - (+) - 3-methoxy-Ot-methylbenzylamine were added to the ambient temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 272 mg (0.66 mmol) of compound K-2012, as a pale yellow syrup, with a yield of 38% NMR at 500 MHz 7.51 (1H, s), 7.43-7.45 (1H, m), 7.35-7.40 (2H, m), 7.23 (1H, dd, J = 7.5 Hz, J = 7.5 Hz), 6.87-6.89 ( 2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.93 (2H, t, J = 7.5 Hz), 2.46-2.51 (1H , m), 2.40-2.44 (1H, m), 1.61-1.67 (2H, m), 1.38-1.50 (7H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 411.

EXAMPLE 51 SYNTHESIS OF K-2015 445 mg (2.35 mmol) of 2-bromobenzenethiol was dissolved in 10 ml of acetonitrile and then 420 mg (3.04 mmol) of potassium carbonate and 0.22 ml (2.64 mmol) of l-bromo-2-chloroethane were successively added thereto, the room temperature. The resulting mixture was stirred at the same temperature for 4 hours. After confirming that the reaction was complete by TLC, 315 mg (2.28 mmol) of potassium carbonate and 250 mg (1.65 mmol) of (R) - (+) - 3-methoxy-6-methylbenzylamine were added to the room temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 120 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 207 mg (0.57 mmol) of compound K-2015, as a pale yellow syrup, with a yield of 34%. %. NMR at 500 MHz 7.53 (1H, d, J = 8.0 Hz), 7.18-7.26 (4H, m), 6.87-6.88 (2H, m), 6.78-6.81 (1H, m), 3.81 (1H, s), 3.04 (2H, t, J = 7.0 Hz), 3.76 (1H, c, J = 6.5 Hz), 2.67-2.81 (2H, m), 1.73 (1H, s), 1.35 (3H, d, J = 6.5 Hz ), m / z = 365, 367.

EXAMPLE 52 SYNTHESIS OF K-2016 517 mg (2.73 mmol) of 2-bromobenzenethiol was dissolved in 10 ml of acetonitrile and then 475 mg (3.44 mmol) of potassium carbonate and 0.31 ml (3.05 mmol) of 1,3-dibromopropane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 4 hours. After confirming that the reaction was complete by TLC, 352 mg (2.76 mmol) of potassium carbonate and 250 mg (1.65 mmol) of (R) - (+) - 3-methoxy-Carnetylbenzylamine were added at room temperature , to the reaction system, and the resulting mixture was stirred at 100 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 249 mg (0.66 mmol) of the compound K-2016, as a pale yellow syrup, with a yield of 40% NMR at 500 MHz 7.52 (1H, d, J = 7.5 Hz), 7.22-7.26 (3H, m), 7.00 (1H, ddd, J = 7.5 Hz, J = 7.5 Hz, J = 2.0 Hz), 6.88 (1H, d, J = 7.5 Hz), 6.87 (1H, s), 6.77 (1H, dd, J = 7.5 Hz, J = 2.0 Hz), 3.81 (3H, s), 3.73 (1H, c, J = 7.0 Hz), 2.90-3.02 ( 2H, m), 2.55-2.69 (2H, m), 1.80-1.86 (2H, m), 1.46 (1H, s), 1.34 (3H, d, J = 7.0 Hz), m / z = 379, 3.81.

EXAMPLE 53 SYNTHESIS OF K-2017 505 mg (2.67 mmoles) of 2-bromobenzenethiol was dissolved in 10 ml of acetonitrile and then 445 mg (3.22 mmoles) of potassium carbonate and 0.35 ml (2.93 mmoles) of 1,4-dibromobutane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 4 hours. After confirming that the reaction was complete by TLC, 330 mg (2.39 mmol) of potassium carbonate and 250 mg (1.65 mmol) of (R) - (+) - 3-methoxy-G-methylbenzylamine were added to the ambient temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 311 mg (0.79 mmol) of compound K-2017, as a pale yellow syrup, with a yield of 48%. %. NMR at 500 MHz 7.52 (1H, d, J = 8.0 Hz), 7.19-7.25 (3H, m), 7.00 (1H, ddd, J = 8.0 Hz, J = 8.0 Hz, J = 2.0 Hz), 6.87-6.88 (2H, m), 6. 78 (1H, dd, J = 2.0 Hz, J = 8.0 Hz), 3.80 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.90 (2H, t, J = 7.5 Hz), 2.43-2.56 (2H, m), 1.68-1.73 (2H, m), 1.68-1.73 (2H, m), 1.58-1.67 (2H , m), 1.47 (1H, s), 1.34 (3H, d, J = 6.5 Hz), m / z = 393, 395.

EXAMPLE 54 SYNTHESIS OF K-2018 445 mg (2.35 mmol) of 2-bromobenzenethiol was dissolved in 10 ml of acetonitrile and then 407 mg (2.95 mmol) of potassium carbonate and 0.31 ml (2.60 mmol) of 1,5-dibromopentane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 4 hours. After confirming that the reaction was complete by TLC, 330 mg (2.39 mmol) of potassium carbonate and 220 mg (1.46 mmol) of (R) - (+) - 3-methoxy-CX-methylbenzylamine were added to the ambient temperature, to the reaction system, and the resulting mixture was stirred at 95 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 307 mg (0.75 mmol) of compound K-2018, as a pale yellow syrup, with a yield of 52 %. NMR at 500 MHz 7.52 (1H, d, J = 6.5 Hz), 7.18-7.25 (3H, m), 6.99 (1H, dd, J = 7.5 Hz, J = 7.5 Hz), 6.87-6.89 (2H, m) , 6.78 (1H, dd, J = 7.5 Hz, J = 2.0 Hz), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.90 (2H, c, J = 7.5 Hz), 2.41-2.51 (2H, m), 1.65-1.69 (2H, m), 1.44-1.53 (5H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 409.

EXAMPLE 55 SYNTHESIS OF K-2027 (N-f5- [(4-CHLOROPHENYL) UNCLE] PENTIL) -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMINE) 550 mg (3.80 mmol) of 4-chlorobenzenethiol was dissolved in 6.0 ml of acetonitrile and then 520 mg (3.76 mmol) of potassium carbonate and 0.52 ml (3.82 mmol) of 1,5-dibromopentane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was completed by TLC, 241 mg (1.74 mmol) of potassium carbonate and 0.31 ml (1.92 mmol) of (R) - (+) -1- (1-naphthyl) ethylamine, at room temperature, was added to the reaction system, and stirred the resulting mixture at 95 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 288 mg (0.75 mmol) of compound K-2027, as a pale yellow syrup, with a yield of 40%. %. NMR at 500 MHz 8.17 (1H, d, J = 8.0 Hz), 7.87 (1H, d, J = 7.5 Hz), 7. 74 (1H, d, J = 9.0 Hz), 7.63 (1H, d, J = 9.0 Hz), 7.63 (1H, d, J = 7.5 Hz), 7.45-7.52 (3H, m), 7.19-7.23 (4H, m), 4.61 (1H, c, J = 6.5 Hz), 2.85 (2H, t, J = 7.2 Hz), 2.50- 2.61 (2H, m), 1.41-1.63 (7H, m), 1.48 (3H, d, J = 6.5 Hz), m / z = 383.

EXAMPLE 56 SYNTHESIS OF K-2030 420 mg (3.27 mmol) of 3-chlorophenol was dissolved. in 9.0 ml of acetonitrile and then 1.19 g (8.61 mmoles) of potassium carbonate and 0.41 ml (4.93 mmoles) of l-bromo-2-chloroethane were added successively at room temperature. The resulting mixture was stirred at 70 ° C for 24 hours. After confirming that the reaction was complete by TLC, 1.70 g (12.3 mmol) of potassium carbonate and 0.45 ml (2.79 mmol) of (R) - (+) -1- (1-naphthyl) were added to the reaction system. ethylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 120 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 321 mg (0.99 mmol) of compound K-2030, as a pale yellow syrup, in a yield of 35 g. %. NMR at 500 MHz 8.21 (1H, d, J = 8.5 Hz), 7.87 (1H, d, J = 7.5 Hz), 7.75 (1H, d, J = 8.0 Hz), 7.69 (1H, d, J = 8.0 Hz ), 7.46-7.53 (3H, m), 7.18 (1H, dd, J = 8.0 Hz), 6.89-3.93 (2H, m), 6.76-6.78 (1H, dd, J = 1.5 Hz, J = 8.0 Hz) , 4.71 (1H, c, J = 6.5 Hz), 4.04 (2H, t, J = 5.3 Hz), 2.90-3.00 (2H, m), 1.78 (1H, s), 1.53 (3H, d, J = 6.5 Hz), m / z = 325.

EXAMPLE 57 SYNTHESIS OF K-2033 470 mg (3.03 mmol) of 4-nitrobenzenethiol was dissolved in 7.0 ml of acetonitrile and then 450 mg (3.26 mmol) of potassium carbonate and 0.36 ml (3.01 mmol) of 1,4-dibromobutane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 3 hours. After confirming that the reaction was complete by TLC, 250 mg (1.81 mmol) of potassium carbonate and 250 mg (1.65 mmol) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 206 mg (0.57 mmol) of compound K-2033, as a yellow syrup, with a yield of 35% . NMR at 500 MHz 8.11 (2H, d, J = 9.0 Hz), 7.29 (2H, d, J = 9.0 Hz), 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.88 (1H, d , J = 8.0 Hz), 6.87 (1H, s), 6.79 (1H, dd, J = 8.0 Hz, J = 2.5 Hz), 3.81 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.99 (2H, t, J = 7.5 Hz), 2.44-2.60 (2H, m), 1.71-1.76 (2H, m), 1.60-1.66 (3H, m), 1.35 (3H, d, J = 6.5 Hz) , m / z = 360.

EXAMPLE 58 SYNTHESIS OF K-2034 520 mg (3.35 mmol) of 4-nitrobenzenethiol was dissolved in 7.0 ml of acetonitrile and then 492 mg (3.56 mmol) of potassium carbonate and 0.46 ml (3.38 mmol) of 1,5-dibromopentane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 3 hours. After confirming that the reaction was complete by TLC, 300 mg (2.17 mmoles) of potassium carbonate and 300 mg (1.98 mmoles) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 102 mg (0.27 mmol) of compound K-2034, as a yellow syrup, with a yield of 14%. NMR at 500 MHz 8.11 (2H, d, J = 9.5 Hz), 7.28 (2H, d, J = 9.5 Hz), 7.24 (1H, dd, J = 7.8 Hz, J = 7.8 Hz), 6.87-6.89 (2H , m), 6.77-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.99 (2H, c, J = 7.5 Hz), 2.49-2.52 (1H, m), 2.41-2.45 (1H, m), 1.67-1.72 (2H, m), 1.45-1.53 (5H, m), 1.35 (3H, d, J = 6.5 Hz), m / z = 374.

EXAMPLE 59 SYNTHESIS OF K-2035 460 mg (2.96 mmol) of 4-nitrobenzenethiol was dissolved in 7.0 ml of acetonitrile and then 432 mg (3.13 mmol) of potassium carbonate and 0.46 ml (2.99 mmol) of 1,6-dibromohexane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 3 hours. After confirming that the reaction was complete by TLC, 120 mg (0.86 mmol) of potassium carbonate and 230 mg (1.52 mmol) of (R) - (+) - 3-methoxy-G- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 133 mg (0.342 mmol) of compound K-2035, as a yellow syrup, in a yield of 23% . NMR at 500 MHz 8.12 (2H, d, J = 9.0 Hz), 7.29 (2H, d, J = 9.0 Hz), 7.24 (1H, dd, J = 8.0 Hz, J = 7.8 Hz), 6.88 (1H, d , J = 8.0 Hz), 6.88 (1H, s), 6.77-6.79 (1H, m), 3.81 (3H, s), 3.73 (1H, c, J = 6.5 Hz), 2.99 (2H, t, J = 7.5 Hz), 2.40-2.53 (2H, m), 1.67-1.73 (2H, m), 1.41-1.50 (5H, m), 1.25-1.36 (2H, m), 1.35 (3H, d, J = 6.5 Hz ), m / z = 388.

EXAMPLE 60 SYNTHESIS OF K-2040 520 mg (4.06 mmol) of 4-fluorobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 864 mg (6.26 mmol) of potassium carbonate and 0.49 ml (4.12 mmol) of 1,4-dibromobutane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 10 hours. After confirming that the reaction was complete by TLC, 320 mg (2.32 mmol) of potassium carbonate and 310 mg (2.05 mmol) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 170 mg (0.51 mmol) of compound K-2040, as a pale yellow syrup, in a yield of 25%. %. NMR at 500 MHz 7.28-7.32 (2H, m), 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 6.95-6.70 (2H, m), 6.86-6.87 (2H, m), 6.76- 6.79 (1H, m), 3.80 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.83 (2H, dd, J = 7.0 Hz, J = 7.0 Hz), 2.47-2.52 (1H, m ), 2.39-2.44 (1H, m), 1.52-1.64 (5H, m), 1.33 (3H, d, J = 6.5 Hz), m / z = 333.

EXAMPLE 61 SYNTHESIS OF K-2041 590 mg (4.61 mmol) of 4-fluorobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 340 mg (2.46 mmol) of potassium carbonate and 0.63 ml (4.62 mmol) of 1,5-dibromopentane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 3 hours. After confirming that the reaction was complete by TLC, 340 mg (2.46 mmol) of potassium carbonate and 350 mg were added to the reaction system. (2.31 mmoles) of (R) - (+) - 3-methoxy-GÉ-methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 245 mg (0.71 mmol) of compound K-2041, as a pale yellow syrup, with a yield of 30%. %. NMR at 500 MHz 7.29-7.32 (2H, m), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.96-6.99 (2H, m), 6.86-6.88 (2H, m), 6.77- 6.79 (1H, m), 3.81 (3H, s), 3.71 (1H, c, J = 7.0 Hz), 2.83 (2H, t, J = 7.2 Hz), 2.45-2.50 (1H, m), 2.38-2.43 (1H, m), 1.54-1.60 (2H, m), 1.38-1.48 (3H, m), 1.34 (3H, d, J = 7.0 Hz), m / z = 347.

EXAMPLE 62 SYNTHESIS OF K-2045 650 mg (3.44 mmol) of 3-bromobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 524 mg (3.79 mmol) of potassium carbonate and 0.29 ml (3.48 mmol) of l-bromo-2-chloroethane were successively added thereto. the room temperature. The resulting mixture was stirred at the same temperature for 3 hours. After confirming that the reaction was complete by TLC, 280 mg (2.02 mmol) of potassium carbonate and 420 mg (2.78 mmol) of (R) - (+) - 3-methoxy-0t- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 120 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 185: 1) to thereby give 395 mg (1.23 mmol) of compound K-2045, as a pale yellow syrup, in a yield of 44%. %. NMR at 500 MHz 7.43 (1H, s), 7.28 (1H, d, J = 8.0 Hz), 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, d, J = 8.0 Hz ), 7.19 (1H, dd, J = 7.5 Hz, J = 7.5 Hz), 6.87 (1H, d, J = 7.5 Hz), 6.86 (1H, s), 6.77 (1H, dd, J = 7.5 Hz, J = 1.5 Hz), 3.80 (3H, s), 3.74 (1H, c, J = 6.5 Hz), 3.02 (2H, t, J = 6.5 Hz), 2.66-2.77 (2H, m), 1.68 (1H, s ), 1.34 (3H, d, J = 6.5 Hz), m / z = 365, 367.

EXAMPLE 63 SYNTHESIS OF K-2046 580 mg (3.06 mmol) of 3-bromobenzenethiol was dissolved in 9.0 ml of acetonitrile and then 432 mg (3.13 mmol) of potassium carbonate and 0.31 ml (3.05 mmol) of 1,3-dibromopropane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 5 hours. After confirming that the reaction was complete by TLC, 280 mg (2.02 mmol) of potassium carbonate and 230 mg (1.52 mmol) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 213 mg (0.56 mmol) of compound K-2046, as a pale yellow syrup, with a yield of 37% NMR at 500 MHz 7.40-7.41 (1H, m), 7.18-7.28 (3H, m), 7.11 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.88 (2H, m), 6.75- 6.79 (1H, m), 3.80 (3H, s), 3.72 (1H, c, J = 7.0 Hz), 2.88 (2H, m), 2.49-2.54 (1H, m), 2.41-2.46 (1H, m) , 1.54-1.69 (2H, m), 1.34 (3H, d, J = 7.0 Hz), m / z = 379, 381.

EXAMPLE 64 SYNTHESIS OF K-2047 470 mg (2.49 mmol) of 3-bromobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 347 mg (2.51 mmol) of potassium carbonate and 0.30 ml (2.51 mmol) of 1,4-dibromobutane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 5 hours. After confirming that the reaction was complete by TLC, 320 mg (2.32 mmol) of potassium carbonate and 200 mg were added to the reaction system. (1.32 mmol) of (R) - (+) - 3-methoxy-O-methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 185 mg (0.47 mmol) of compound K-2047, as a pale yellow syrup, in a yield of 36. %. NMR at 500 MHz 7.19-7.28 (3H, m), 7.02-7.13 (2H, m), 6.86-6.88 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.77 (1H , c, J = 6.5 Hz), 1.76-1.79 (2H, m), 2.89-3.01 (2H, m), 2.60-2.65 (1H, m), 2.51-2.56 (1H, m), 2.31-2.42 (2H , m), 1.52 (1H, s), 1.33 (3H, d, J = 6.5 Hz), m / z = 393, 395.

EXAMPLE 65 SYNTHESIS OF K-2048 530 mg (2.80 mmol) of 3-bromobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 395 mg (2.86 mmol) of potassium carbonate and 0.38 ml (2.78 mmol) of 1,5-dibromopentane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 2 hours. After confirming that the reaction was complete by TLC, 213 mg (1.54 mmoles) of potassium carbonate and 200 mg were added to the reaction system. (1.32 mmol) of (R) - (+) - 3-methoxy-G ^ -methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 226 mg (0.55 mmol) of compound K-2048, as a pale yellow syrup, with a yield of 42%. %. NMR at 500 MHz 7.41 (1H, s), 7.18-7.28 (3H, m), 7.11 (1H, dd, J = 7.5 Hz, J = 7.5 Hz), 6.88 (2H, d, J = 7.5 Hz), 6.87 (1H, s), 6.78 (1H, dd, J = 7.5 Hz, J = 2.5 Hz), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.89 (2H, d, J = 7.2 Hz), 2.47-2.51 (1H, m), 2.40-2.43 (1H, m), 1.62 (2H, m), 1.40-1.50 (5H, m), 1.234 (3H, d, J = 6.5 Hz).

EXAMPLE 66 SYNTHESIS OF K-2049 600 mg (3.17 mmoles) of 3-bromobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 500 mg (3.62 mmoles) of potassium carbonate and 0.50 ml (3.25 mmoles) of 1,6-dibromohexane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 2 hours. After confirming that the reaction was complete by TLC, 205 mg (1.48 mmol) of potassium carbonate and 250 mg were added to the reaction system. (1.66 mmoles) of (R) - (+) - 3-methoxy-O ^ -methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 267 mg (0.63 mmol) of compound K-2049, like a pale yellow syrup, with a yield of 38%. NMR at 500 MHz 7.41 (1H, dd, J = 1.8 Hz, J = 1.8 Hz), 7.19-7.27 (3H, m), 7.11 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.87 -6.89 (2H, m), 6.77 (1H, dd, J = 8.0 Hz, J = 2.5 Hz), 3.81 (3H, s), 3.72 (1H, t, J = 6.5 Hz), 2.88 (2H, t, J = 7.8 Hz), 2.39-2.51 (2H, m), 1.50-1.65 (2H, m), 1.25-1.49 (7H, m), 1.34 (3H, d, J = 6.5 Hz).

EXAMPLE 67 SYNTHESIS OF K-2050 525 mg (2.78 mmol) of 3-bromobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 325 mg (2.36 mmol) of potassium carbonate and 0.47 ml (2.75 mmol) of 1,7-dibromoheptane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 182 mg (1.32 mmol) of potassium carbonate and 210 mg (1.39 mmol) of (R) - (+) - 3-methoxy-O -methylbenzylamine were added to the reaction system, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 260 mg (0.60 mmol) of compound K-2050, as a pale yellow syrup, with a yield of 43%. %. NMR at 500 MHz 7.41 (1H, dd, J = 2.0 Hz, J = 2.0 Hz), 7.23-7.27 (2H, m), 7.18-7.21 (1H, m), 7.11 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6. 90-6.93 (2H, m), 6.80 (1H, dd, J = 8.0 Hz, J = 2.5 Hz), 3.82 (3H, s), 3.77-3.80 (1H, m), 2.88 (2H, t, J = 7.5 Hz), 2.42-2.54 (2H, m), 1.58-1.64 (2H, m), 1.50-1.55 (1H, m), 1.35-1.45 (4H, m), 1.42 (3H, d, J = 7.5 Hz ), 1.21-1.29 (4H, m), m / z = 4.35, 437.

EXAMPLE 68 SYNTHESIS OF K-2051 610 mg (3.22 mmol) of 3-bromobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 490 mg (3.55 mmol) of potassium carbonate and 0.59 ml (3.20 mmol) of 1,8-dibromooctane were successively added thereto. room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 218 mg (1.58 mmol) of potassium carbonate and 250 mg (1.66 mmol) of (R) - (+) - 3-methoxy-Carnetylbenzylamine were added to the reaction system. at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 170 mg (0.38 mmol) of compound K-2051, as a pale yellow syrup, with a yield of 24 g. %. NMR at 500 MHz 7.41-7.42 (1H, m), 7.19-7.27 (3H, m), 7.11 (1H, dd, J = 7.8 Hz, J = 7.8 Hz), 6.90-6.92 (2H, m), 6.79 ( 1H, dd, J = 7.8 Hz, J = 2.0 Hz), 3.82 (3H, s), 3.76-3.82 (1H, m), 2.89 (2H, t, J = 7.8 Hz), 2.42-2.53 (2H, m ), 1.59-1.65 (2H, m), 1.49 (1H, m), 1.41 (3H, d, J = 6.5 Hz), 1.36-1.43 (4H, m), 1.22-1.28 (6H, m), m / z = 449, 451.

EXAMPLE 69 SYNTHESIS OF K-2052 (N-T5- [(4-FLUOROPHENYL) UNCLE] PENTIL) -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMIN) 460 mg (3.60 mmol) of 4-fluorobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 500 mg (3.62 mmol) of potassium carbonate and 0.50 ml (3.67 mmol) of 1,5-dibromopentane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 210 mg (1.52 mmole) of potassium carbonate and 300 mg (1.86 mmole) of (R) - (+) -1- (1-naphthyl) were added to the reaction system. ethylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 210 mg (0.57 mmol) of compound K-2052, like a pale yellow syrup, with a yield of 31%. NMR at 500 MHz 8.17 (1H, d, J = 8.0 Hz), 7.87 (1H, d, J = 8.5 Hz), 7.74 (1H, d, J = 8.0 Hz), 7.62 (1H, d, J = 8.0 Hz ), 7.41-7.50 (5H, m), 7.29 (2H, d, J = 8.5 Hz), 4.61 (1H, c, J = 6.5 Hz), 2.82 (2H, t, J = 7.5 Hz), 2.56-2.57 (2H, m), 2.37-2.43 (2H, m), 1.40-1.59 (5H, m), 1.46 (3H, d, J = 6.5 Hz), m / z = 367.

EXAMPLE 70 SYNTHESIS OF K-2055 408 mg (2.29 mmol) of 4-trifluoromethylbenzenethiol was dissolved in 10.0 ml of acetonitrile and then 330 mg (2.39 mmol) of potassium carbonate and 0.23 ml (2.28 mmol) of 1,3-dibromopropane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 172 mg (1.25 mmol) of potassium carbonate and 210 mg were added to the reaction system. (1.39 mmoles) of (R) - (+) - 3-methoxy-G-methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 122 mg (0.33 mmol) of compound K-2055, as a pale yellow syrup, with a yield of 24% NMR at 500 MHz 7.44-7.50 (2H, m), 7.32 (1H, d, J = 8.5 Hz), 7.23 (1H, dd, J = 8.5 Hz, J = 8.5 Hz), 7.17-7.20 (1H, m), 6.85-6.88 (2H, m), 6.77-6.79 (1H, m), 3.80 (3H, s), 3.70-3.74 (1H, m), 1.77-1.83 (2H, m), 1.34 (3H, d, J = 6.5 Hz), 1.26-1.26 (1H, m), m / z = 369.

EXAMPLE 71 SYNTHESIS OF -2056 487 mg (2.74 mmol) of 4-trifluoromethylbenzenethiol was dissolved in 10.0 ml of acetonitrile and then 374 mg (2.71 mmol) of potassium carbonate and 0.33 ral (2.77 mmol) of 1,4-dibromobutane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 172 mg (1.25 mmole) of potassium carbonate and 250 mg (1.65 mmole) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours.

After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 152 mg (0.40 mmol) of compound K-2056, as a pale yellow syrup, in a yield of 24 g. %. NMR at 500 MHz 7.49 (2H, d, J = 8.5 Hz), 7.32 (1H, d, J = 8.0 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.88 (2H , m), 6.76-6.79 (1H, m), 3.80 (1H, s), 3.71 (1H, c, J = 6.5 Hz), 2.92-2.95 (2H, t, J = 7.5 Hz), 1.55-1.73 ( 4H, m), 1.47 (1H, s), 1.33 (3H, d, J = 6.5 Hz), 2.50-2.55 (1H, m), 2.42-2.47 (1H, m), m / z = 383.

EXAMPLE 72 SYNTHESIS OF K-2057 560 mg (3.15 mmoles) of 4-trifluoromethylbenzenethiol was dissolved in 10.0 ml of acetonitrile and then 440 mg (3.19 mmoles) of potassium carbonate and 0.43 ml (3.16 mmoles) of 1,5-dibromopentane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 240 mg (1.74 mmole) of potassium carbonate and 290 mg (1.92 mmole) of (R) - (+) - 3-methoxy-GI- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 129 mg (0.32 mmol) of compound K-2057, like a pale yellow syrup, with a yield of 17%. NMR at 500 MHz 7.49 (2H, d, J = 8.5 Hz), 7.31 (2H, d, J = 8.0 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.89 (2H , m), 6.76-6.79 (1H, m), 3.81 (1H, s), 3.71 (1H, c, J = 6.8 Hz), 2.94 (2H, t, J = 7.3 Hz), 2.40-2.51 (2H, m), 1.63-1.68 (2H, m), 1.42-1.51 (5H, s), 14.34 (3H, d, J = 6.8 Hz), m / z = 397.

EXAMPLE 73 SYNTHESIS OF K-2058 500 mg (2.81 mmol) of 4-trifluoromethylbenzenethiol was dissolved in 10.0 ml of acetonitrile and then 420 mg (3.64 mmol) of potassium carbonate and 0.43 ml (2.79 mmol) of 1 were added successively. 6-dibromohexane, at room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 150 mg (1.09 mmoles) of potassium carbonate and 260 mg (1.72 mmoles) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 155 mg (0.38 mmol) of compound K-2058, as a pale yellow syrup, in a yield of 22%. %. NMR at 500 MHz 7.49 (2H, d, J = 8.5 Hz), 7.32 (2H, d, J = 7.0 Hz), 7. 23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.87-6.89 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.94 (2H, t, J = 7.5 Hz), 2.39-2.52 (2H, m), 1.63-1.69 (2H, m), 1.39-1.50 (5H, s), 1.29-1.34 (2H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 411.

EXAMPLE 74 SYNTHESIS OF K-2059 500 mg (2.81 mmol) of 4-trifluoromethylbenzenethiol was dissolved in 10.0 ml of acetonitrile and then 420 mg (3.64 mmol) of potassium carbonate and 0.48 ml (2.81 mmol) of 1,7-dibromoheptane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 150 mg (1.09 mmol) of potassium carbonate and 260 mg were added to the reaction system. (1.72 mmoles) of (R) - (+) - 3-methoxy-Omethylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 204 mg (0.48 mmol) of compound K-2059, as a pale yellow syrup, with a yield of 28%. %. NMR at 500 MHz 7.49 (2H, d, J = 8.5 Hz), 7.32 (2H, d, J = 6.5 Hz), 7.23 (1H, dd, J = 6.0 Hz, J = 6.O Hz), 6.87-6.89 (2H, m), 6.76-6.79 (1H, m), 3.81 (1H, s), 3.73 (1H, c, J = 6.0 Hz), 2.94 (2H, t, J = 6.5 Hz), 2.39-2.51 (2H, m), 1.62-1.68 (2H, m), 1.34-1.48 (9H, m), 1.35 (3H, d, J = 6. = Hz), m / z = 425 EXAMPLE 75 SYNTHESIS OF K-2061 460 mg (3.18 mmol) of 3-chlorobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 440 mg (3.19 mmol) of potassium carbonate and 0.32 ral (3.15 mmol) of 1,3-dibromopropane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 2 hours. After confirming that the reaction had been completed by .TLC, 210 mg (1.52 mmoles) of potassium carbonate and 300 mg (1.99 mmoles) of (R) - (+) - 3-methoxy-OC were added to the reaction system. -methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 272 mg (0.81 mmol) of compound K-2061, like a pale yellow syrup, with a yield of 41%. 500 MHz NMR 7.11-7.27 (5H, m), 6.86-6.88 (2H, m), 6.77-6.79 (1H, m), 3.81 (1H, s), 3.70 (1H, c, J = 6.5 Hz), 2.89-3.01 (2H, m), 2.60-2.65 (1H, m), 2.51-2.56 (1H, m), 1.75-1.81 (2H, m), 1.47 (1H, s), 1.33 (3H, d, J = 6.5 Hz), m / z = 335.

EXAMPLE 76 SYNTHESIS OF K-2066 575 mg (3.21 mmol) of 2,5-dichlorobenzenethiol was dissolved in 11.0 ml of acetonitrile and then 440 mg (3.19 mmol) of potassium carbonate and 0.26 ml (3.12 mmol) of l-bromo-2-chloroethane were successively added. , at room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 225 mg (1.63 mmol) of potassium carbonate and 340 mg (2.25 mmol) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 100 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 182 mg (0.51 mmol) of compound K-2066, as a pale yellow syrup, in a yield of 23%. %. NMR at 500 MHz 7.21-7.30 (3H, m), 7.19 (1H, d, J = 2.5 Hz), 6.88-6.89 (2H, m), 6.77 (1H, dd, J = 8.5 Hz, J = 2.5 Hz) , 3.81 (3H, s), 3.76 (1H, c, J = 6.5 Hz), 3.04 (2H, t, J = 7.0 Hz), 2.72-2.83 (2H, m), 1.66 (1H, s), 1.36 ( 3H, d, J = 6.5 Hz), m / z = 355, 357.

EXAMPLE 77 SYNTHESIS OF K-2075 702 mg (3.71 mmol) of 2-bromobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 525 mg (3.80 mmol) of potassium carbonate and 0.50 ml (3.67 mmol) of 1,5-dibromopentane were added successively at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 247 mg (1.79 mmol) of potassium carbonate and 0.30 ml (1.86 mmol) of (R) - (+) -1- (1-naphthyl) were added to the reaction system. ethylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give 144 mg (0.34 mmol) of compound K-2075, as a pale yellow syrup, with a yield of 18. %. NMR at 500 MHz 8.18 (1H, d, J = 8.5 Hz), 7.87 (1H, d, J = 8.5 Hz), 7.64 (1H, d, J = 8.5 Hz), 7.74 (1H, d, J = 8.5 Hz ), 7.45-7.53 (4H, m), 7.13-7.25 (2H, m), 6.99 (1H, ddd, J = 1.5 Hz, J = 6.0 Hz, J = 6.0 Hz), 4.62 (1H, c, J = 7.0 Hz), 2.89 (2H, t, J = 7.5 Hz), 2.52-2.63 (2H, m), 1.66-1.71 (2H, m), 1.45-1.59 (5H, m), 1.49 (3H, d, J = 7.0 Hz), m / z = 427.

EXAMPLE 78 SYNTHESIS OF K-2076 N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (5- { [4- (TRIFLUOROMETHYL) PHENYL] THIN PENTIL) AMINE) 510 mg (2861 mmoles) of 4-trifluoromethylbenzenethiol was dissolved in 12.0 ml of acetonitrile and then 400 mg (2.89 mmoles) of potassium carbonate and 0.39 ml (2.86 mmoles) of 1,5-dibromopentane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 200 mg (1.45 mmol) of potassium carbonate and 28 ml (i.73 mmol) of (R) - (+) -1- (1) were added to the reaction system. -naphthyl) ethylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 180: 1) to thereby give 53 mg (0.13 mmol) of compound K-2076, as a pale yellow syrup, with a yield of 7% NMR at 500 MHz 8.18 (1H, d, J = 8.5 Hz), 7.87 (1H, d, J = 7.0 Hz), 7.74 (1H, d, J = 6.5 Hz), 7.63 (1H, d, J = 6.5 Hz ), 7.45-7.52 (5H, m), 7.30 (2H, d, J = 8.0 Hz), 4.62 (1H, c, J = 6.5 Hz), 2.93 (2H, t, J = 6.5 Hz), 2.93 (2H , t, J = 7.0 Hz), 2.51-2.63 (2H, m), 1.63-1.69 (2H, m), 1.44-1.56 (5H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 417.

EXAMPLE 79 SYNTHESIS OF K-2078 469 mg (2.62 mmoles) of 3,4-dichlorobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 400 mg (2.89 mmoles) of potassium carbonate and 0.27 ml (2.67 mmoles) of 1,3-dibromopropane were successively added thereto. the room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 180 mg (1.30 mmol) of potassium carbonate and 240 mg were added to the reaction system. (1.59 mmoles) of (R) - (+) - 3-methoxy-O-methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 143 mg (0.39 mmol) of compound K-2078, as a pale yellow syrup, in a yield of 25%. %. NMR at 500 MHz 7.36 (1H, d, J = 1.5 Hz), 7.31 (1H, d, J = 8.5 Hz), 7.24 (1H, dd, J = 6.5 Hz, J = 6.5 Hz), 7.10 (1H, dd , J = 8.5 Hz, J = 1.5 Hz), 6.85-6.88 (2H, m), 6.77-6.79 (1H, m), 3.81 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.88 -3.00 (2H, m), 2.50-2.64 (2H, m), 1.71-1.81 (2H, m), 1.52 (1H, s), 1.33 (3H, d, J = 6.5 Hz), m / z = 369 371 EXAMPLE 80 SYNTHESIS OF K-2079 556 mg (3.11 mmol) of 3,4-dichlorobenzenethiol was dissolved in 12.0 ml of acetonitrile and then 412 mg (2.99 mmol) of potassium carbonate and 0.37 ml (3.10 mmol) of 1,4-dibromobutane were successively added thereto. 'the room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 242 mg (1.75 mmoles) of potassium carbonate and 280 mg (1.85 mmoles) of (R) - (+) - 3-methoxy-OC- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 156 mg (0.41 mmol) of compound K-2079, as a pale yellow syrup, in a yield of 22%. %. NMR at 500 MHz 7.34 (1H, d, J = 2.5 Hz), 7.31 (1H, d, J = 8.5 Hz), 7.23 (1H, dd, J = 7.5 Hz, J = 7.5 Hz), 7.10 (1H, dd , J = 8.5 Hz, J = 2.5 Hz), 6.87 (1H, d, J = 7.5 Hz), 6.86 (1H, s), 6.76-6.79 (1H, m), 3.80 (3H, s), 3.71 (1H , c, J = 7.0 Hz), 2.87 (2H, t, J = 7.0 Hz), 2.41-2.54 (2H, m), 1.53-1.68 (4H, m), 1.46 (1H, s), 1.33 (3H, d, J = 7.0 Hz), m / z = 383, 385.

EXAMPLE 81 SYNTHESIS OF K-2080 515 mg (2.88 mmol) of 3,4-dichlorobenzenethiol was dissolved in 11.0 ml of acetonitrile and then 410 mg (2.97 mmol) of potassium carbonate and 0.39 ml (2.86 mmol) of 1,5-dibromopentane were successively added thereto. the room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 230 mg (1.66 mmoles) of potassium carbonate and 260 mg (1.72 mmoles) of (R) - (+) - 3-methoxy-O- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours.

After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 250 mg (0.63 mmol) of compound K-2080, as a pale yellow syrup, with a yield of 37 %. NMR at 500 MHz 7.34 (1H, d, J = 2.5 Hz), 7.31 (1H, d, J = 8.5 Hz), 7.22-7.25 (1H, m), 7.09 (1H, dd, J = 2.5 Hz, J = 8.5 Hz), 6.88 (1H, d, J = 8.5 Hz), 6.87 (1H, s), 6.78 (1H, dd, J = 8.5 Hz, J = 2.5 Hz), 3.81 (3H, s), 3.72 (1H , c, J = 6.5 Hz), 2.87 (2H, t, J = 8.0 Hz), 2.39-2.52 (2H, m), 1.59-1.64 (2H, m), 1.38-1.51 (5H, m), 1.34 ( 3H, d, J = 6.5 Hz), m / z = 395, 397.

EXAMPLE 82 SYNTHESIS OF K-2082 720 mg (4.02 mmol) of 3,4-dichlorobenzenethiol was dissolved in 15.0 ml of acetonitrile and then 550 mg (3.98 mmol) of potassium carbonate and 0.64 ml (3.75 mmol) of 1,7-dibromoheptane were successively added thereto. the room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 230 mg (1.66 mmol) of potassium carbonate and 360 mg (2.38 mmol) of (R) - (+) - 3-methoxy-GC- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 253 mg (0.59 mmol) of compound K-2082, as a pale yellow syrup, in a yield of 25%. %. NMR at 500 MHz 7.35 (1H, d, J = 2.5 Hz), 7.31 (1H, d, J = 8.0 Hz), 7.22-7.25 (1H, m), 7.10 (1H, dd, J = 8.5 Hz, J = 2.5 Hz), 6.88-6.90 (1H, m), 6.90 (1H, s), 6.78 (1H, dd, J = 2.5 Hz, J = 8.5 Hz), 3.81 (3H, s), 3.75 (1H, c, J = 6.5 Hz), 2.87 (2H, t, J = 7.3 Hz), 2.40-2.52 (2H, m), 1.58-1.64 (2H, m), 1.48 (1H, s), 1.34-1.64 (2H, m ), 1.37 (3H, d, J = 6.5 Hz), 1.24-1.33 (4H, m), m / z = 425, 427.

EXAMPLE 83 SYNTHESIS OF K-2084 540 mg (3.02 mmol) of 2,6-dichlorobenzenethiol was dissolved in 11.0 ml of acetonitrile and then 420 mg (3.04 mmol) of potassium carbonate and 0.31 ml (3.05 mmol) of 1,3-dibromopropane were successively added thereto. the room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 234 mg (1.69 mmoles) of potassium carbonate and 230 mg (1.52 mmoles) of (R) - (+) - 3-methoxy-C- were added to the reaction system. methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 182 mg (0.49 mmol) of compound K-2084, as a pale yellow syrup, with a yield of 32%. %. NMR at 500 MHz 7.6 (2H, d, J = 8.0 Hz), 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.16 1H, dd, J = 8. O Hz, J = 8.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 6.85 (HI, s), 6.76-6.78 (1H, m), 3.81 (3H, s), 3.70 (1H, c, J = 6.0 Hz), 2.89-2.98 (2H, m), 2.52-2.64 (2H, m), 1.65-1.71 (2H, m), 1.46 (1H, s), 1.32 (3H, d, J = 6. O Hz), m / z = 369, 371.

EXAMPLE 84 SYNTHESIS OF K-2085 500 mg (2.79 mmoles) of 2,6-dichlorobenzenethiol was dissolved in 10.0 ml of acetonitrile and then 400 mg (2.90 mmoles) of potassium carbonate and 0.33 ml (2.76 mmoles) of 1,4-dibromobutane were successively added thereto. the room temperature. The resulting mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by TLC, 230 mg (1.65 mmole) of potassium carbonate and 250 mg (1.65 mmole) of (R) - (+) - 3-methoxy- (X) were added to the reaction system. -methylbenzylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 24 hours.After completing the reaction, the reaction was cooled by allowing it to stand at room temperature After pouring water, the mixture was subjected to extraction of water. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the organic residue was purified by silica gel column chromatography (chloroform). methanol = 150: 1) to thereby give 293 mg (0.76 mmol) of compound K-2085, as a pale yellow syrup, with a yield of 46% 500 MHz NMR 7.36 (2H, d, J = 7.5 Hz), 7.23 (1H, dd, J = 7.5 Hz, J = 7.5 H z), 7.16 (1H, dd, J = 7.5 Hz, J = 7.5 Hz), 6.85-6.87 (1H, m), 6.86 (1H, s), 6.76-6.78 (1H, m), 3.81 (3H, s ), 3.70 (1H, c, J = 6.5 Hz), 2.89 (2H, t, J = 7.0 Hz), 2.38-2.51 (2H, m), 1.51-1.63 (4H, m), 1.49 (1H, s) , 1.32 (3H, d, J = 6.5 Hz).

EXAMPLE 85 SYNTHESIS OF K-2087 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (4-T [3- (TRIFLUOROMETHYL) PHENYL] -TIO-BUTIL) AMIN) 670 mg (3.76 mmol) of 3-trifluoromethylbenzenethiol was dissolved in 14.0 ml of acetonitrile and then 516 mg (3.73 mmol) of potassium carbonate and 0.45 ml (3.77 mmol) of 1,4-dibromobutane were successively added at the temperature ambient. The resulting mixture was stirred at the same temperature for 2 hours. After confirming that the reaction was complete by TLC, 300 mg (2.17 mmol) of potassium carbonate and 0.30 ml (1.86 mmol) of (R) - (+) -1- (1-naphthyl) were added to the reaction system. ) ethylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 12 hours.

After completing the reaction, the reaction was cooled by allowing it to stand at room temperature. After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 150: 1) to thereby give 298 mg (0.74 mmol) of compound K-2087, as a pale yellow syrup, with a yield of 40%. %. NMR at 500 MHz 8.18 (1H, d, J = 8.0 Hz), 7.86-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 7.5 Hz), 7.45 -7.52 (4H, m), 7.41-7.43 (1H, m), 7.33-7.39 (2H, m), 4.62 (1H, c, J = 6.5 Hz), 2.92 (2H, d, J = 7.0 Hz), 2.60-2.65 (1H, m), 2.52-2.57 (1H, m), 1.63-1.72 (4H, m), 4.54 (1H, s), 1.48 (3H, d, J = 6.5 Hz), m / z = 403 EXAMPLE 86 SYNTHESIS OF K-2117 ((R) -N- [1- (1 '-NAFTYL) ETHYL] -2- (2', 5'-DICHLOROPHENYLTHY) ETHYLAMINE) .10 g (28.5 mmol) of 2,5-dichlorobenzenethiol were dissolved in 30 ml of acetonitrile and then 4.20 g (30.4 mmol) of potassium carbonate and 2.45 ml (29.4 mmol) of l-bromo-2-chloroethane were successively added. , at room temperature. The resulting mixture was stirred while cooling with ice for 2 hours. After confirming that the reaction was complete by TLC, 4.0 g (28.9 mmol) of potassium carbonate and 3.70 mL (22.9 mmol) of (R) - (+) -1- (1-naphthyl) were added to the reaction system. ethylamine, at room temperature, and the resulting mixture was stirred at 100 ° C for another 120 hours. After completing the reaction the reaction was cooled by letting it stand at room temperature. ' After pouring water, the mixture was subjected to separation extraction with chloroform and washed with a saturated aqueous solution of sodium chloride. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give 5.70 g (15.2 mmol) of compound K-2117, like a pale yellow syrup, with a yield of 66%. NMR at 500 MHz 8.17 (1H, d, J = 8.5 Hz), 7.85-7.87 (1H, m), 7.73 (1H, d, J = 8.0 Hz), 7.65 (1H, d, J = 7.5 Hz), 7.44 -7.52 (4H, m), 7.26 (1H, d, J = 8.5 Hz), 7.20 (1H, d, J = 2.5 Hz), 7.05 (1H, dd, J = 2.5 Hz, J = 8.5 Hz), 4.65 (1H, c, J = 6.5 Hz), 3.09 (2H, m), 2.82-2.91 (2H, m), 1.68 (1H, s), 1.51 (3H, d, J = 6.5 Hz), m / z = 375, 377.

EXAMPLE 87 SYNTHESIS OF CHLORHYDRATE OF K-2117 7.01 g (18.6 mmol) of compound K-2117 was dissolved in 40 ml of a 30% solution of hydrochloric acid-methanol (HCl-MeOH) and stirred at room temperature for 5 minutes. After the reaction was completed, the reaction system was concentrated in situ under reduced pressure, to thereby completely eliminate the hydrochloric acid-methanol solution. The residue was filtered through a Kiriyama funnel and the resultant crystals were washed with hexane. In this manner, 5.87 g (14.2 mmol) of K-2117 hydrochloride was obtained, in the form of white crystals, at a yield of 76%. m / z = 375, 377. NMR with 1H (400 MHz) 10.97 (1H, broad s), 10.30 (1H, broad s), 8.18 (1H, d, J = 7.32 Hz), 7.88-7.97 (3H, m ), 7.53-7.66 (3H, m), 7.31 (1H, d, J = 2.4 Hz), 7.14 (1H, d, J = 8.56 Hz), 7.01 (1H, dd, J = 1.36 Hz, J = 8.56 Hz ), 5.23-5.27 (1H, m), 3.55-3.61 (2H, m), 2.95-3.10 (2H, m), 2.04 (3H, d, J = 6.60 Hz).

EXAMPLE 88 SYNTHESIS OF K-2177 1.0 g (0.51 mmol) of dibenzylamine and 0.85 ml (0.61 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform and 0.505 g (0.56 mmol, 1.1 molar equivalent) of acryloyl chloride was added while cooling with ice. The resulting mixture was stirred at room temperature for 30 minutes. After the reaction was completed, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water. After drying over sodium sulfate, the solvent was distilled off under reduced pressure. The crystals thus obtained were purified by column chromatography [chloroform-methanol silica gel] to give 1.085 g (85.0%) of colorless prisms. 50 mg (0.20 mmol) of the compound thus obtained and 41.0 mg (0.24 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in 2 ml of chloroform-methanol were dissolved and let stand at room temperature for a week. After the reaction was complete, the solvent was distilled off under reduced pressure. The oil thus obtained (silica gel, chloroform-methanol) was purified by column chromatography to thereby give 50.9 mg of K-2177, as a colorless oil in 60.5% yield. MS m / z 422 (M +). 1 H NMR: 1.53 (3H, d, J = 6.7 Hz, CH3), 2.60-2.70 (2H, m, CH2), 2.86-2.96 (2H, m, CH2), 4.42 (2H, s, CH2), 4.62 (2H, s, CH2), 4.69 (1H, c, J = 6.7 Hz, CH), 7.13 (2H, d, J = 7.3 Hz, Ar-H), 7.21 (2H, d, J = 6.7 Hz, Ar-H), 7.27-7-36 (6H, m, Ar-H), 7.45-7.50 (3H, m, Ar-H), 7.70 (1H, d, J = 6.7 Hz, Ar-H), 7.74 (1H, d, J = 7.9 Hz, Ar-H), 7.86 (1H, dd, J = 1.8, 6.7 Hz, Ar-H), 8.16 (1H, d, J = 7.9 Hz, Ar-H).

EXAMPLE 89 SYNTHESIS OF K-2246 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (4-T [4- (TRIFLUOROMETHYL) PHENYL] TIO BUTIL) MINE) 960 mg (5.39 mmol) of 4-trifluoromethylthiophenol was dissolved in 8 ml of acetonitrile. Subsequently, 802 mg (5.80 mmoles) of potassium carbonate and 0.65 ml (5.44 mmoles) of 1,4-dibromobutane were added at room temperature, and the obtained mixture was stirred at the same temperature for 30 minutes. After confirming that the reaction was complete by means of TLC, 5 ml of acetonitrile, 693 mg (5.01 mmoles) of potassium carbonate and 0.49 ml (2.96 mmoles) of (R) - (+) -1- ( 1-naphthyl) ethylamine, at room temperature, and the mixture obtained was stirred at 85 ° C for 12 hours. After completing the reaction, the reaction was cooled by allowing it to stand at room temperature and water was poured. The mixture was then subjected to separating extraction with chloroform and with a saturated aqueous solution of sodium chloride and the organic layer thus obtained was dried over sodium sulfate. The organic layer was further concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (80 g, chloroform / methanol = 200: 1) to thereby give 210 mg (0.52 mmol, 17.6%) of K-2246, like a transparent syrup, pale yellow. Subsequently, the K-2246 thus obtained was dissolved in a 10% solution of hydrochloric acid in methanol, stirred for 5 minutes and then concentrated at said reduced pressure. The crystals thus formed were washed with diethyl ether to thereby give 104 mg (0.24 mmol, 8.1%) of K-2246 hydrochloride, as white crystals. NMR with 1H (400 MHz) 10.6 (1H, broad s), 10.1 (1H, broad s), 8.24 (1H, d, J = 7.08 Hz), 7.99 (1H, d, J = 8.52 Hz), 7.90.- 7.96 (2H, m), 7.55-7.67 (3H, m), 7.39-7.41 (2H, m), 7.17-7.19 (2H, m), 5.17-5.24 (1H, m), 2.73-2.84 (4H, m) , 2.11-2.18 (2H, m), 2. 06 (3H, d, J = 6.60 Hz), 1.57-1.62 (4H, m), m / z = 403.

EXAMPLE 90 SYNTHESIS OF K-2076 1,040 g (5.83 mmoles) of 4-trifluoromethylthiophenol were dissolved in 10 ml of acetonitrile. Subsequently, 1024 g (7.40 mmoles) of potassium carbonate and 0.80 ml (5.87 mmoles) of 1,5-dibromopentane were added at room temperature, and the obtained mixture was stirred at the same temperature for 1 hour. After confirming that the reaction was complete by means of TLC, 8 ml of acetonitrile, 853 mg (6.17 mmol) of potassium carbonate and 0.60 ml (3.63 mmol) of (R) - (+) were added at room temperature. ) -1- (1-naphthyl) ethylamine, and the mixture obtained was stirred at 85 ° C, for 12 hours. After the reaction was complete, the mixture was cooled by allowing it to stand at room temperature and water was poured. It was then subjected to separating extraction with chloroform and with a saturated aqueous solution of sodium chloride, and the organic layer thus obtained was dried over sodium sulfate. Further, the organic layer was concentrated under reduced pressure and the obtained residue was purified by means of silica gel column chromatography (100 g, chloroform / methanol = 200/1) to thereby give 240 mg (0.57 mmol, 17.7% ) of K-2076, as a clear, pale yellow syrup. The K-2076 thus obtained was subsequently dissolved in a 10% solution of hydrochloric acid in methanol, stirred for 5 minutes and then concentrated under reduced pressure. The crystals thus formed were washed with diethyl ether to give 115 mg (0.25 mmol, 6.9%) of K-076 hydrochloride, as white crystals. NMR with 1H (400 MHz) 10.55 (1H, broad s), 10.01 (1H, broad s), 8.24 (1H, d, J = 7.08 Hz), 7.89.-7.99 (3H, m), 7.52-7.66 (3H , m), 7.44 (2H, d, J = 8.32 Hz), 7.23 (2H, d, J = 8.32 Hz), 5.19 (1H, broad s), 2.82 (2, t, J = 7.08 Hz), 2.74 ( 2H, broad s), 2.04 (3H, d, J = 6.36 Hz), 1.96-2.04 (2H, m), 1.50-1.57 (2H, m), 1.30-1.38 (2H, m), m / z = 417 .

EXAMPLE 91 SYNTHESIS OF K-2243 (N ', N' -DI (4-CHLOROBENCIL) -3-C [(IR) -1- (1-NAFTHYL) ETHYL] AMINO ^ PROPANAMIDE) It was added to 500 mg (3.56 mmol) of p-chlorobenzaldehyde and 503.6 mg (3.56 mmol, 1.0 molar equivalent) of p-chlorobenzylamine, 1.26 ml (2.47 mmol, 1.2 molar equivalents) of titanium tetraisopropoxide, and the mixture was stirred well. obtained at room temperature for 4 hours. After the reaction was completed, the reaction mixture was dissolved in methanol and 538.7 mg (14.24 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The obtained mixture was stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed under reduced pressure. Ethyl acetate and water were poured into the residue and filtered through celite. The residue was washed with ethyl acetate and then the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and washed over sodium sulfate. After distilling off the solvent under reduced pressure, the oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give 819 mg (86.6%) of compound 124, as a colorless oil. MS m / z: 266. NMR with ^ S: 3.74 (4H, d, J = 2.7, CH2x2), 7.24-6.30 (8H, m Ar-H). 500 mg (1.88 mmol) of compound 124 above and 0.31 ml (2.26 mmol, 1.2 molar equivalent) of triethylamine in chloroform were dissolved, and 187.1 mg (2.07 mmol, 1.1 equivalent) was added while cooling with ice. molar) of acryloyl chloride. The mixture obtained was then stirred at room temperature for 30 minutes. After the reaction was completed, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After the solvent was distilled off under reduced pressure, the oil obtained was purified by column chromatography [silica gel], chloroform] to thereby give 570.3 mg (94.4%) of compound 125, as a colorless oil. MS m / z: 320. NMR with 1H O: 4.47 (2H, s, CH2), 4.59 (2H, s, CH2), 5.77 (1H, dd, J = 2.9, 9.8 Hz, CH = CH2), 6.52 ( 1H, d, J = 2.7 Hz, CH = CH2), 6.54 (1H, d, J = 9.8 Hz, CH = CH2), 7.08 (2H, d, J = 8.1 Hz, Ar-H), 7.18 (2H, d, J = 8.1 Hz, Ar-H), 7.29 (2H, d, J = 8.1 Hz, Ar-H), 7.33 (2H, d, J = 8.1 Hz, Ar-H). 100 mg (0.31 mmol) of compound 125 above and 64.2 mg (0.38 mmol, 1.2 molar equivalents) of (R) - (+) - (1-naphthyl) ethylamine in chloroform / methanol were dissolved. (4: 1) and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 106.6 mg (69.5%) of K-2243 as a colorless oil. MS m / z: 491. NMR with 1HS: 1.51 (3H, d, J = 6.6 Hz, CH3), 2.60 (2H, t, J = 6.1, CH2), 2.82-2.96 (2H, m, CH2), 4.35 (2H, s, CH2), 4.53 (2H, s, CH2), 4.66 (1H, c, J = 6.6 Hz, CH), 7.03 (2H, d, J = 8.3 Hz, Ar-H), 7.12 (2H , d, J = 8.3 Hz, Ar-H), 7.27 (2H, d, J = 8.3 Hz, Ar-H), 7.30 (2H, d, J = 8.3 Hz, Ar-H), 7.47 (1H, t , J = 5.1 Hz, Ar-H), 7.48 (1H, t, J = 5.1 Hz, Ar-H), 7.49 (1H, t, J = 5.1 Hz, Ar-H), 7.67 (1H, d, J = 5.1 Hz, Ar-H), 7.74 (1H, d, J = 5.1 Hz, Ar-H), 7.87 (1H, t, J = 7.5 Hz, Ar-H), 7.16 (1H, d, J = 7.5 Hz, Ar-H).

EXAMPLE 92 SYNTHESIS OF K-2257 (N ', N' -DI [4- (TRIFLUOROMETOXY) BENCIL] -3- f [(IR) -1- (1-NAFTHYL) ETHYL] AMINO ^ PROPANAMIDE) It was added to 500 mg (2.62 mmoles) of p- (trifluoromethoxy) benzylamine and 497.3 mg (2.62 mmoles, 1.0 molar equivalent) of p- (trifluoromethoxy) benzaldehyde, 0.926 ml (3.14 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide, and the mixture thus obtained was stirred at room temperature for 4 hours. After the reaction was complete, the reaction mixture was dissolved in methanol and 396.5 mg (10.48 mmol, 4.0 molar equivalents) of sodium borohydride was added thereto. The obtained mixture was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were poured into the residue and filtered through celite. The residue was washed with ethyl acetate and then the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give 835.2 mg (87.5%) of compound 126, as a colorless oil. MS m / z: 365. NMR with H: 3.80 (4H, s, CH2x2), 7.17 (4H, d, J = 8.1H, Ar-H), 7.36 (4H, d, J = 8.1 Hz, Ar-H ). 500 mg (1.37 mmol) of compound 126 above and 0.23 ml (1.64 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 136.3 mg (1.51 mmol, 1.1 molar equivalent) was added while cooling with ice. ) of acryloyl chloride. The mixture obtained was then stirred at room temperature for 30 minutes. After the reaction was completed, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give 519.3 mg (90.5%) of compound 127, as a colorless oil. MS m / z: 419. 1 H NMR: 4.53 (2H, s, CH2), 4.64 (2H, s, CH2), 5.79 (1H, dd, J = 2.7, 9.5 Hz, CH = CH2), 6.53 ( 1H, d, J = 2.7 Hz, CH = CH2), 6.56 (1H, d, J = 9.5 Hz, CH = CH2), 7.15-7.31 (8H, m, Ar-H). 450 mg (1.07 mmol) of the compound 127 mentioned above and 220.7 mg (1.29 mmol, 1.2 molar equivalents) of (R) - (+) - (1-naphthyl) ethylamine in chloroform / methanol (4: 1) were dissolved and let stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 363 mg (57.3%) of K-2257 as a colorless oil. MS m / z: 590. NMR with 1H 6: 1.50 (3H, d, J = 6.6 Hz, CH3), 2.60 (2H, t, J = 5.9, CH2), 2.84-2.97 (2H, m, CH2), 4.41 (2H, s, CH2), 4. 57 (2H, s, CH2), 6.65 (1H, c, J = 6.6 Hz, CH), 7.12-7.29 (2H, m, Ar-H), 7.44-7.51 (3H, m, Ar-H), 7.66 (1H, d, J = 6.8 Hz, Ar-H), 7.73 (1H, d, J = 8.3 Hz, Ar-H), 7.86 (1H, dd, J = 2.4 Hz, 7.1 Hz, Ar-H), 8.17 (1H, d, J = 7.1 Hz, Ar-H).

EXAMPLE 93 SYNTHESIS OF K-2259 (N1, N '-DI [4- (TRIFLUOROMETHYL) BENCIL] -3- f [(IR) -1- (1-NAFTHYL) ETHYL] AMIN0) PRQPANAMIDE) It was added to 500 mg (2.85 mmol) of p- (trifluoromethyl) benzylamine and 497.1 mg (2.85 mmol, 1.0 molar equivalent) of p- (trifluoromethyl) benzaldehyde, 1.1 ml (3.43 mmol, 1.2 molar equivalents) of titanium tetraisopropoxide and The mixture thus obtained was stirred at room temperature for 4 hours. After the reaction was completed, the reaction mixture was dissolved in methanol and 431.3 mg (11.4 mmol, 4.0 molar equivalent) of sodium borohydride was added. The mixture thus obtained was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were poured into the residue and filtered through celite. The residue was washed with ethyl acetate and then the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give 458.7 mg (48.3%) of compound 128, as a colorless oil. MS m / z: 333. 1H NMR ': 3.86 (4H, s, CH2x2), 7.47 (4H, d, J = 8.1H, Ar-H), 7.59 (4H, d, J = 8.1 Hz, Ar- H). 450 mg (1.35 mmoles) of compound 128 mentioned above and 0.23 ml (1.62 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform and added, while cooling with ice, 134.4 mg (1.48 mmoles, 1.1 molar equivalent) ) of acryloyl chloride. The mixture obtained was then stirred at room temperature for 30 minutes. After the reaction was completed, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent under reduced pressure, the oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give 519.3 mg (99.3%) of compound 129, as a colorless oil. MS m / z: 387. NMR with 1H or: 4.59 (2H, s, CH2), 4.70 (2H, s, CH2), 5.80 (1H, dd, J = 3.7, 8.8 Hz, CH = CH2), 6.54 ( 1H, d, J = 3.7 Hz, CH = CH2), 6.56 (1H, d, J = 8.8 Hz, CH = CH2), 7.23-7.64 (8H, m, Ar-H). 800 mg (2.06 mmol) of the compound 129 mentioned above and 424.0 mg (2.48 mmol, 1.2 molar equivalents) of (R) - (+) - (1-naphthyl) ethylamine in chloroform / methanol were dissolved. (4: 1) and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 580.7 mg (50.3%) of K-2259, as a colorless oil. MS m / z: 558. 1 H NMR -: 1-51 (3 H, d, J = 6.6 Hz, CH 3), 2.60 (2H, t, J = 6.1, CH2), 2.85-2.98 (2H, m, CH2), 4.47 (2H, s, CH2), 4.64 (2H, s, CH2), 4.65 (1H, c, J = 6.6 Hz, CH), 7.23 (2H, d, J = 8.3 Hz, Ar-H), 7.31 (2H, d, J = 8.3 Hz, Ar-H), 7.44-7.51 / 3H, m, Ar-H), 7.55 (2H, d, J = 8.3 Hz, Ar-H), 7.59 (2H, d, J = 8.3 Hz, Ar-H), 7.66 (1H, d, J = 8.1 Hz, Ar-H), 7.74 (1H, d, J = 8.1 Hz, Ar-H), 7.87 (1H, dd, J = 2.4 Hz, 8.1 Hz , Ar-H), 8.18 (1H, dd, J = 2.4, 8.1 Hz, Ar-H).

EXAMPLE 94 SYNTHESIS OF K-2247 (N1 -BENCIL-N '- (4-CHLOROBENCIL) -3 - { [(IR) -1- (1-NAFTHYL) ETHYL] AMINO PROPANAMIDE) To 500 mg (3.56 mmol) of 4-chlorobenzaldehyde and 381.2 mg (3.56 mmol, 1.0 molar equivalent) of benzylamine, 1.26 ml (4.27 mmol, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred to the room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 538.7 mg (14.24 mmol, 4.0 equivalent) was added. molars) of sodium borohydride. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate., and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give 572.6 mg (69.5%) of a colorless oil, compound 201. MS m / z: 231. 300 mg was dissolved in chloroform (1.29). mmoles) of the dibenzylamine compound 201 and 0.22 ml (1.55 mmoles, 1.2 molar equivalents) of triethylamine, and 128.9 mg (1.42 mmoles, 1.1 molar equivalent) of acryloyl chloride was added while cooling with ice. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was completed, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 372.1 mg (100.0%) of a colorless oil, compound 202. MS m / z: 285. It was dissolved in chloroform / methanol (4: 1), 100.3 mg (0.35 mmol, 1.2 molar equivalents) of the conjugated ketone compound 202 and 50 mg (0.29 mmol) of '(R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week . After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2247 (64.5 mg, 40.2 %). MS m / z: 456. NMR with H 5: 1.53 (3H, d, J = 6.7 Hz, CH3), 2.60-2.67 (2H, m, CH2), 2.86-2.95 (2H, m, CH2), 4.39 ( 2H, d, J = 18.3 Hz, CH2), 4.58 (2H, d, J = 13.4 Hz, CH2), 4.69 (1H, c, J = 6.7 Hz, CH), 7.04 (1H, d, J = 8.5 Hz , Ar-H), 7.12 (1H, d, J = 6.7 Hz, Ar-H), 7.15 (1H, d, J = 8.5 Hz, Ar-H), 7.20 (1H, d, J = 6.7 Hz, Ar -H), 7.28-7.36 (5H, m, Ar-H), 7.46-7.51 (3H, m, Ar-H), 7.69 (1H, d, J = 7.3 Hz, Ar-H), 7.75 (1H, d, J = 7.9 Hz, Ar-H), 7.87 (1H, dd, J = 1.8 Hz, 7.9 Hz, Ar-H), 8.17 (1H, d, J = 7.9 Hz, Ar-H).

EXAMPLE 95 SYNTHESIS OF K-2248 It was added to 500 mg (3.20 mmol) of 2-naphthaldehyde and 343. 1 mg (3.20 mmoles, 1.0 molar equivalent) of benzylamine, 1.13 ml (3.84 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide and the mixture thus obtained was stirred at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 484.2 mg (12.8 mmol, 4.0 molar equivalents) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was completed, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give 769.1 mg (97.1%) of a colorless oil 203. MS m / z: 247. 500 mg (2.02 mmol) was dissolved in chloroform. of the dibenzylamine compound 203 and 0.34 ml (2.43 mmol, 1.2 molar equivalents) of triethylamine, and 201.3 mg (2.22 mmol, 1.1 molar equivalent) of acryloyl chloride was added while cooling with ice. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 579.7 mg (95.0%) of a colorless oil 204. MS m / z: 301. dissolved 105.8 mg (0.35 mmol, 1.2 molar equivalents) of the conjugated ketone compound 204 and 50 mg (0.29 mmol) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) , and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2247 (69.8 mg, 42.0 %). MS m / z: 472. NMR with 1H & 1.52 (3H, dd, J = 6.7, 8.5 Hz, CH3), 2.66-2.69 (2H, m, CH2), 2.89-3.00 (2H, m, CH2) , 4.51 (2H, d, J = 65.3 Hz, CH2), 4.67 (1H, c, J = 36.7 Hz, CH), 4.75 (2H, J = 48.2 Hz, CH2), 7.16 (1H, d, J = 7.3 Hz, Ar-H), 7.22-7.39 (5H, m, Ar-H), 7.43-7.52 (5H, m, Ar-H), 7.58 (1H, d, J = 25.6 Hz, Ar-H) , 7.68-7.88 (6H, m, Ar-H), 8.17 (1H, dd, J = 7.9, 21.4 Hz, Ar-H ,.

EXAMPLE 96 SYNTHESIS OF K-2249 To 500 mg (3.56 mmol) of 2-chlorobenzaldehyde and 381.2 mg (3.56 mmol, 1 mole equivalent) of benzylamine, 1.26 ml (4.17 mmoles, 1.2 molar equivalent) of titanium tetraisopropoxide was added, and the mixture was stirred at room temperature for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 538.7 mg (14.24 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was stirred at room temperature for 12 hours. After the reaction was completed, the solvent was removed by distillation under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 205 (427.7 mg, 51.9%). MS m / z: 231. 300 mg (1.29 mmol) of dibenzylamine compound 205 and 0.22 ml (1.55 mmol, 1.2 molar equivalent) of triethylamine were dissolved in chloroform, and 128.9 mg (1.42 mmol) was added while cooling with ice. , 1.1 molar equivalent) of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate.

After distilling off the solvent, the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil 206 (358.8 mg, 96.8%). MS m / z: 285. 100.3 mg (0.35 mmol, 1.2 molar equivalents) of the conjugated ketone compound 206 and 50 mg (0.29 mmol) (R) - (+) -1- (1-naphthyl) ethylamine, were dissolved in chloroform / methanol (4: 1) and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give 67.8 mg (50.8%) of a colorless oil K. 2249 MS m / z: 456. NMR with H 6: 1.53 (3H, dd, J = 6.7, 4.3 Hz, CH3), 2.51-2.74 (2H, m, CH2), 2.85-2.98 (2H, m, CH2), 4.50 (2H, d, J = 9.8 Hz, CH2), 4.64 (1H, s, CH2), 4.66-4.70 (1H, m, CH), 4.78 (1H, s, CH2), 7.15 (1H, d, J = 7.9 Hz, Ar-H), 7.19-7.39 (8H, m, Ar-H), 7.45-7.51 (3H, m, Ar-H), 7.70 (1H, t, J = 7.9 Hz, Ar-H) , 7.74 (1H, dd, J = 3.7, 7.9 Hz, Ar-H), 7.87 (1H, dd, J = 7.3 Hz, Ar-H), 8.17 (1H, t, J = 7.3 Hz, Ar-H) , EXAMPLE 97 SYNTHESIS OF K-2250 (N '-BENCIL-N' - (3, 4-DICHLOROBENCIL) -3-T [(IR) -1- (1-NAFTHYL) ETHYL] AMIN ?.}. PROPANAMIDE) To 300 mg (2.83 mmoles) of benzaldehyde and 497.7 mg (2.83 mmoles, 1.0 molar equivalent) of 3,4-dichlorobenzylamine, 1.00 ml (3.39 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 482.2 mg (11.32 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 207 (568 mg, 75.5%). MS m / z: 266. 300 mg (1.13 mmol) of the dibenzylamine compound 207 and 0.189 ml (1.35 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 112.3 mg were added while cooling with ice. 1.24 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 208 (358.3 mg 99.3%). MS m / z: 320. It was dissolved in chloroform / methanol (4: 1), 100 mg (0.31 mmol) of the conjugated ketone compound 208 and 64.2 mg (0.38 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2250 (96.5 mg, 62.9 %). MS m / z: 491. NMR with 1H 6: 1.51 (3H, d, J = 6.6 Hz, CH3), 2.49-2.68 (2H, m, CH2), 2.82-2.96 (2H, m, CH2), 4.38 ( 2H, d, J = 32.43 Hz, CH2), 4.54 (1H, s, CH2), 4.67 (2H, d, J = 41.5 Hz, CH2), 4.66 (1H, c, J = 6.6 Hz, CH), 7.11 (1H, d, J = 6.6 Hz, Ar-H), 7.19 (1H, d, J = 6.8 Hz, Ar-H), 7.21-7.41 (6H , m, Ar-H), 7.43-7.51 (3H, m, Ar-H), 7.67 (1H, dd, J = 2.0, 7.1 Hz, Ar-H), 7.74 (1H, d, J = 8.3 Hz, Ar-H), 7.86 (1H, dd, J = 2.2 Hz, 8.1 Hz, Ar-H), 8.16 (1H, d, J = 7.3 Hz, Ar-H).

EXAMPLE 98 SYNTHESIS OF K-2251 To 300 mg (2.83 mmoles) of benzaldehyde and 497.7 mg (2.83 mmoles, 1.0 molar equivalent) of 2,4-dichlorobenzylamine, 1.00 ml (3.39 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 482.2 mg (11.32 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 209 (469 mg, 62.4%). MS m / z: 266. 300 mg (1.13 mmol) of the dibenzylamine compound 209 and 0.189 ml (1.35 mmol, 1.2 molar equivalents) of triethylamine was dissolved in chloroform, and 112.3 mg was added while cooling with ice. 1.24 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 210 (311.6 mg 86.3%). MS m / z: 320. It was dissolved in chloroform / methanol (4: 1), 100 mg (0.31 mmol) of the conjugated ketone compound 210 and 64.2 mg (0.38 mmol, 1.2 molar equivalent) of (R) - (+ ) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2251 (126.7 mg, 82.6 %). MS m / z: 491. NMR with H d: 1.51 (3H, dd, J = 2.5, 6 .6? Lz, CH3), 2.51-2.53 (1H, m, CH2), 2.64-2.68 (1H, m, CH2), 2.84-2.96 (2H, m, CH2), 4.46 (2H, d, J = 13.4 Hz, CH2), 4.60 (1H, s, CH2), 4.65-4.68 (1H, m, CH), 4.69 ( 1H, s, CH2), 7.13 (1H, d, J = 7.3 Hz, Ar-H), 7.17-7.39 (7H, m, Ar-H), 7.44-7.50 (3H, m, Ar-H), 7.67 (1H, t, J = 7.3 Hz, Ar-H), 7.73 (1H, dd, J = 3.7, 7.9 Hz, Ar-H), 7.86 (1H, d, J = 7.3 Hz, Ar-H), 8.16 (1H, d, J = 7.9 Hz, Ar-H).

EXAMPLE 99 SYNTHESIS OF K-2252 To 500 mg (4.71 mmoles) of benzaldehyde and 667.2 mg (4.71 mmoles, 1.0 molar equivalent) of 3-chlorobenzylamine, 1.67 ml (5.65 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred to the room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 712.7 mg (18.84 mmol, 4.0 molar equivalents) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate., and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 211 (930.5 mg, 85.2%). MS m / z: 231. 500 mg (2.16 mmol) of the dibenzylamine compound 211 and 0.36 ml (2.59 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform and 214.8 mg (214.8 mg) was added while cooling with ice. 2.37 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 212 (308.5 mg 50.0%). MS m / z: 285. It was dissolved in chloroform / methanol (4: 1), 100 mg (0.35 mmol) of the conjugated ketone compound 212 and 71.8 mg (0.42 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2252 (85.5 mg, 53.2 %). MS m / z: 456. NMR with Hj j: 1.50 (3H, d, J = 6.6 Hz, CH3), 2.61 (2H, dt, J = 6.1, 21.0 Hz, CH2), 2.82-2.96 (2H, m , CH2), 4.40 (2H, d, J = 19.3 Hz, CH2), 4.60 (2H, d, J = 13.7 Hz, CH2), 4.66 (1H, c, J = 6.6 Hz, CH), 7.13 (2H, d, J = 7.1 Hz, Ar-H), 7.20-7.37 (7H, m, Ar-H), 7.43-7.51 (3H, m, Ar-H), 7.68 (1H, d, J = 8.1 Hz, Ar-H), 7.73 (1H, d, J = 8.1 Hz, Ar-H), 7.86 (1H, dd, J = 2.2, 7.3 Hz, Ar-H), 8.17 (1H, d, J = 7.6 Hz, Ar-H).

EXAMPLE 100 SYNTHESIS OF K-2253 To 500 mg (3.56 mmoles) of 3-chlorobenzaldehyde and 503.7 mg (3.56 mmoles, 1.0 molar equivalent) of 3-chlorobenzylamine, 1.26 ml (4.27 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred. at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 538.7 mg (14.24 mmol, 4.0 molar equivalents) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 213 (756.5 mg, 80.3%). MS m / z: 266. 500 mg (1.88 mmol) of dibenzylamine compound 213 and 0.31 ml (2.26 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 187.1 mg (187.1 mg) was added while cooling with ice. 2.07 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 214 (595.3 mg 98.8%). MS m / z: 320. It was dissolved in chloroform / methanol (4: 1), 100 mg (0.31 mmol) of the conjugated ketone compound 214 and 64.2 mg (0.48 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2253 (96.5 mg, 62.9 %). MS m / z: 491. NMR with 1H 6: 1.51 (3H, d, J = 6.1 Hz, CH3), 2.58 (2H, d, J = 6.1 Hz, CH2), 2.85-2.97 (2H, m, CH2) , 4.38 (2H, s, Hz, CH2), 4.57 (2H, d, J = 3.1 Hz, CH2), 4.65 (1H, c, J = 6.1 Hz, CH), 6.99 (1H, d, J = 5.5 Hz , Ar-H), 7.08 (1H, d, J = 6.1 Hz, Ar-H), 7.11 (1H, s, Ar-H), 7.20 (1H, s, Ar-H), 7.23-7.27 (4H, m, Ar-H), 7.44-7.49 (3H, m, Ar-H), 7.67 (1H, d, J = 7.3 Hz, Ar-H), 7.72 (1H, d, J = 7.9 Hz, Ar-H ), 7.85 (1H, d, J = 7.9 Hz, Ar-H), 8.18 (1H, d, J = 7.9 Hz, Ar-H).

EXAMPLE 101 SYNTHESIS OF K-2254 500 mg (3.56 mmol) of 2-chlorobenzaldehyde and 503.6 mg (3.56 mmol, 1.0 molar equivalent) of 2-chlorobenzylamine, 1.25 ml (4.27 mmol, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred. at room temperature, during 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 538.7 mg (14.2 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto.

The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate., and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 215 (632.6 mg, 66.9%). MS m / z: 266. 400 mg (1.50 mmol) of dibenzylamine compound 215 and 0.25 ml (1.80 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 149.7 mg was added while cooling with ice. 1.65 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 216 (391.7 mg 81.2%). MS m / z: 320. It was dissolved in chloroform / methanol (4: 1), 100 mg (0.31 mmol) of the conjugated ketone compound 216 and 64.2 mg (0.38 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2254 (72.7 mg, 47.4 %). MS m / z: 491. NMR with 1H 6: 1.49 (3H, d, J = 6.6 Hz, CH3), 2.53-2.60 (2H, m, CH2), 2.83-2.93 (2H, m, CH2), 4.57 ( 2H, s, CH2), 4.64 (1H, c, J = 6.6 Hz, CH2), 4.77 (2H, s, CH2), 7.13-7.38 (8H, m, Ar-H), 7.44-7.51 (3H, m , Ar-H), 7.66 (1H, d, J = 6.6 Hz, Ar-H), 7.72 (1H, d, J = 8.1 Hz, Ar-H), 7.85 (1H, dd, J = 2.4, 7.1 Hz , Ar-H), 8.14 (1H, dd, J = 2.2, 7.1 Hz, Ar-H).

EXAMPLE 102 SYNTHESIS OF K-2256 To 484.2 mg (3.90 mmoles) of 4-fluorobenzaldehyde and 500 mg (3.90 mmoles, 1.0 molar equivalent) of 4-fluorobenzylamine, 1.38 ml (4.68 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred. at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 590.1 mg (15.6 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 217 (783.2 mg, 84.0%). MS m / z: 233. 500 mg (2.15 mmoles) of the dibenzylamine compound 217 and 0.36 ml (2.58 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform and 213.6 mg (213.6 mg) was added while cooling with ice. 2.36 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 218 (572.6 mg 86.8%). MS m / z: 287. It was dissolved in chloroform / methanol (4: 1), 800 mg (1.63 mmol) of the conjugated ketone compound 218 and 33.7 mg (1.95 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2256 (375.1 mg, 48.2 %). MS m / z: 458. NMR with U 6: 1.50 (3H, d, J = 6.6 Hz, CH3), 2.60 (2H, t, J = 6.1, CH2), 2.84-2.96 (2H, m, CH2), 4.36 (2H, s, CH2), 4.54 (2H, s, CH2), 4.66 (1H, c, J = 6.6 Hz, CH2), 6.95-7.09 (6H, m, Ar-H), 7.16 (1H, d , J = 8.8 Hz, Ar-H), 7.17 (1H, d, J = 8.8 Hz, J = 8.8 Hz, Ar-H), 7.43-7.51 (3H, m, Ar-H), 7.67 (1H, d , J = 6.6 Hz, Ar-H), 7.73 (1H, d, J = 8.3 Hz, Ar-H), 7.87 (1H, dd, J = 2.4, 7.0 Hz, Ar-H), 8.17 (1H, dd , J = 2.0, 7.3 Hz, Ar-H).

EXAMPLE 103 SYNTHESIS OF K-2261 To 992.7 mg (7.06 mmol) of 3-chlorobenzaldehyde and 1 g (7.06 mmol, 1.0 molar equivalent) of 4-chlorobenzylamine, 2.5 ml (8.47 mmol, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 1.0683 g (28.4 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate., and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 219 (1.5847 g, 84.4%). MS m / z: 266. 1.3 g (4.89 mmoles) of the dibenzylamine compound 219 and 0.82 ml (5.86 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 486.6 mg (486.6 mg) was added while cooling with ice. 5.38 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 220 (1.2967 g 82.7%). MS m / z: 320. It was dissolved in chloroform / methanol (4: 1), 1 g (3.13 mmol) of the conjugated ketone compound 220 and 642.2 mg (3.75 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2261 (624.8 mg, 40.7 %). MS m / z: 491. NMR with 1H 6: 1.50 (3H, d, J = 6.6 Hz, CH3), 2.54-2.63 (2H, m, CH2), 2.82-2.96 (2H, m, CH2), 4.36 ( 2H, d, J = 4.4 Hz, CH2), 4.55 (2H, d, J = 2.9 Hz, CH2), 4.65 (1H, c, J = 6.6 Hz, CH2), 7.04 (2H, d, J = 8.6 Hz , Ar-H), 7.13 (2H, d, J = 8.6 Hz, Ar-H), 7.18-7.31 (4H, m, Ar-H), 7.44-7.51 (3H, m, Ar-H), 7.67 ( 1H, d, J = 7.3 Hz, Ar-H), 7.73 (1H, d, J = 8.1 Hz, Ar-H), 7.85 (1H, dd, J = 2.2, 7.3 Hz, Ar-H), 8.16 ( 1H, d, J = 7.6 Hz, Ar-H).

EXAMPLE 104 SYNTHESIS OF K-2262 (N '- (2-CHLOROBENCIL) -N' - (4-CL0R0BENCIL) -3- I [(IR) -1- (l-NAFTIL) ETHYL] AMIN?) PROPANAMIDE) To 992.7 mg (7.06 mmol) of 2-chlorobenzaldehyde and 1 g (7.06 mmol, 1.0 molar equivalent) of 4-chlorobenzylamine, 2.5 ml (8.47 mmol, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 1.0683 g (28.4 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer was washed with water and with a saturated aqueous solution of sodium chloride and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 221 (673.6 mg, 40.0%). MS m / z: 266. 600 mg (2.26 mmol) of the dibenzylamine compound 221 and 0.38 ml (2.71 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 224.6 mg (224.6 mg) was added while cooling with ice. 2.48 mmoles, 1.1 molar equivalent) of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 222 (684.2 g 94.8%). MS m / z: 320. It was dissolved in chloroform / methanol (4: 1), 500 mg (1.56 mmol) of the conjugated ketone compound 222 and 321.1 mg (1.88 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2262 (552.4 mg, 72.0 %). MS m / z: 491. NMR with 1H 6: 1.56 (3H, d, J = 6.6 Hz, CH3), 2.51-2.72 (2H, m, CH2), 2.83-2.98 (2H, m, CH2), 4.43 ( 2H, s, CH2), 4. 48 (1H, s, CH2), 4.56 (1H, d, J = 4.5 Hz, CH2), 4.68-4.72 (1H, m, CH), 4.73 (1H, d, J = 5.6 Hz, CH2), 7.05 ( 2H, d, J = 8.3 Hz, Ar- H), 7.15 (1H, d, J = 8.3 Hz, Ar-H), 7.20-7.39 (6H, m, Ar-H), 7.45-7.52 (3H, m , Ar-H), 7.68 (1H, d, J = 6.3 Hz, Ar-H), 7.75 (1H, d, J = 8.3 Hz, Ar-H), 7.87 (1H, d, J = 7.1 Hz, Ar -H), 8.14 (1H, d, J = 6.6 Hz, Ar-H).

EXAMPLE 105 SYNTHESIS OF K-2264 (N '- (3, 4-DICHLOROBENCIL) -N' - [(4-TRIFLUOROMETHYL) BENCIL] -3 - T [(IR) -1- (1-NAFTHYL) ETHYL] AMINO PROPANAMIDA) To 1 g (5.71 mmoles) of 3,4-dichlorobenzaldehyde and 1 g (5.71 mmoles, 1.0 molar equivalent) of 4-trifluoromethylbenzylamine, 2.02 ml (6.86 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture was stirred thus obtained at room temperature, for 4 hours. After the reaction was complete, the reaction mixture was dissolved in ethanol and 864.6 mg (22.86 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 223 (1668 g, 87.40%).

MS m / z: 334. NMR with H 6: 3.75 (2H, s, CH2), 3.84 (2H, s, CH2), 7.17 (1H, dd, J = 2.2, 8.3 Hz, Ar-H), 7.39 ( 2H, d, 8.3 Hz, Ar-H), 7.45 (1H, d, J = 8.3 Hz, Ar-H), 7.46 (1H, d, J = 2.2 Hz, Ar-H), 7.59 (2H, d, J = 8.3 Hz, Ar-H). 800 mg (2.39 mmol) of the dibenzylamine compound 223 and 0.4 ml (2.87 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 238.4 mg (2.63 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 224 (930 mg 100.0%). MS m / z: 388. NMR with H 6: 4.54 (2H, d, J = 42.0 Hz, CH2), 4.64 (2H, d, J = 39.0 Hz, CH2), 5.79.5.82 (1H, m, CH = CH2), 6.53-6.60 (2H, m, CH = CH2), 7.23-7.45 (5H, m, Ar-H ), 7.58 (1H, d, J = 7.8 Hz, Ar-H), 7.63 (1H, d, J = 7.8 Hz, Ar-H). It was dissolved in chloroform / methanol (4: 1), 800 mg (2.06 mmol) of the conjugated ketone compound 224 and 387.7 mg (2.26 mmol, 1.1 molar equivalent) of (R) - (+) -1- (1-naphthyl) ) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2264 (807.4 mg, 70.1 %). MS m / z: 559. NMR with 1H 6: 1.51 (3H, d, J = 6.6 Hz, CH3), 2.59 (2H, t, J = 6.1 Hz, CH2), 2.85-2.98 (2H, m, CH2), 4.41 (2H, d, J = 42.0 Hz, CH2), 4.58 (2H, d, J = 38.1 Hz, CH2), 4.66 (1H, c, J = 6.6 Hz, CH2), 7.19 (1H, d, J = 2.0 Hz, Ar-H), 7.22 (1H, d, J = 8.3 Hz, Ar-H), 7.30 (2H, d, J = 8.3 Hz, Ar-H), 7.44-7.52 (3H, m, Ar-H), 7.55 (1H, d, J = 8.3 Hz, Ar-H), 7.59 (1H, d, J = 8.3 Hz, Ar-H), 7.66 (1H, d, J = 7.1 Hz, Ar-H), 7.74 (1H, d, J = 8.3 Hz, Ar- H), 7.86 (1H, dd, J = 2.9, 6.6 Hz, Ar-H), 8.17 (1H, d, J = 8.3 Hz, Ar-H).

EXAMPLE 106 SYNTHESIS OF K-2265 (N ', N' -DI (3, 4-DICHLOROBENCIL) -3-T [(IR) -1- (1-NAFTHYL) ETHYL] AMINO ^ PROPANAMIDE) To 500 mg (2.86 mmoles) of 3,4-dichlorobenzaldehyde and 0.382 ml (2.86 mmoles) of 3,4-dichlorobenzylamine, 1.51 ml (5.14 mmoles, 1.8 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred at room temperature, for 28 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 443 mg (11.44 mmol, 4.0 molar equivalent) of sodium borohydride was added. The mixture thus obtained was then stirred at room temperature for 20 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Chloroform and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with chloroform and the wash liquor was combined with the filtrate and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, hexane-ethyl acetate (9: 1-4: 1)) to thereby give a colorless oil 225 (712.2 mg, 74.3%). MS m / z: 335. NMR with 1H 6: 3.74 (4H, d, J = 2.7 CH2 x 2), 7.17 (2H, dd, J = 2.0, 8.3 Hz, Ar-H), 7.39 (2H, d, 8.3 Hz, Ar-H), 7.44 (2H, d, J = 2.0 Hz, Ar-H). 315 mg (0.94 mmoles) of the dibenzylamine compound 225 and 0.16 ml (1.13 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 94 mg (1.04 mmoles, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride. The mixture obtained was stirred at room temperature for 1 hour. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After removing by 116 After distillation of the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 226 (347.1 mg 94.9%). MS m / z: 389. NMR with H 6: 4.47 (2H, s, CH2), 4.58 (2H, s, CH2), 5.58 (1H, dd, J = 5.9, 6.6 Hz, CH = CH2), 6.52 ( 1H, d, J = 5.9 Hz, CH = CH2), 6.52 (1H, d, J = 6.6 Hz, CH = CH2), 6.99 (1H, d, J = 7.6 Hz, Ar-H), 7.08 (1H, d, J = 7.6 Hz, Ar-H), 7.23 (1H, s, Ar-H), 7.32 (1H, s, Ar-H), 7.39 (1H, d, J = 7.8 Hz, Ar-H), 7.44 (1H, d, J = 7.3 Hz, Ar-H). It was dissolved in chloroform / methanol (4: 1), 280 mg (0.72 mmol) of conjugated ketone compound 226 and 148 mg (0.864 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ) ethylamine and allowed to stand at room temperature for 8 days. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2265 (314.1 mg, 77.9 %). Subsequently, 201.7 mg (0.36 mmol) of K-2265 obtained in a 10% solution of hydrochloric acid / methanol was dissolved and stirred for 10 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to thereby give 188.2 mg (87.6%) of the K-2265 hydrochloride, as colorless crystals.

MS m / z: 560. NMR with H 6: 1-56 (3H, d, J = 6.6 Hz, CH3), 2.55-2.63 (2H, m, CH2), 2.86-2.99 (2H, m, CH2), 4.35 (2H, s, CH2), 4.51 (2H, s, CH2), 4.71 (1H, c, J = 6.6 Hz, CH2), 6.94 (1H, dd, J = 22, 8.3 Hz, Ar-H), 7.04 (1H, dd, J = 2.2, 8.1 Hz, Ar-H), 7.18 1H, d, J = 2.0 Hz, Ar-H), 7.27 (1H, d, J = 2.0 Hz, Ar-H), 7.37 (1H, d, J = 8.1 Hz, Ar-H), 7.40 (1H, d, J = 8.3 Hz, Ar-H), 7.45-7.52 (3H, m, Ar-H), 7.68 (1H, c, J = 6.6 Hz, Ar-H), 7.75 (1H, d, J = 8.1 Hz, Ar-H), 7.87 (1H, dd, J = 2.2, 7.3 Hz, Ar-H), 8.15 (1H, d, J = 7.3 Hz, Ar-H).

EXAMPLE 107 SYNTHESIS OF K-2266 (N1- (4-CHLOROBENCIL) -N '- [(4-TRIFLUOROMETHYL) BENCIL] -3-f [(lR) -l- (1-NAFTHYL) ETHYL] AMIN ?.} PROPANAMIDA) To 1 g (5.74 mmoles) of 4- (trifluoromethyl) benzaldehyde and 813.2 mg (5.74 mmoles, 1.0 molar equivalent) of 4-chlorobenzylamine, 2.03 ml (6.89 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide was added and the mix thus obtained at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 868.6 mg (22.96 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 227 (1.6267 g, 94.5%). MS m / z: 299. NMR with 1H 6: 3.77 (2H, s, CH2), 3.84 (2H, s, CH2), 7.27 (2H, d, J = 9.0 Hz, Ar-H), 7.30 (2H, d, J = 9.0 Hz, Ar-H), 7.46 (2H, d, J = 8.1 Hz, Ar-H), 7.58 (2H, d, J = 8.1 Hz, Ar-H), 800 mg (2.67 mmoles) of the dibenzylamine compound 227 and 0.45 ml (3.20 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 265.7 mg (2.94 mmoles, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After removing the solvent by distillation, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 228 (938.5 mg 99.3%). MS m / z: 353. NMR with H 6: 4.53 (2H, d, J = 26.8 Hz, CH2), 4.65 (2H, d, J = 24.4 Hz, CH2), 5.79 (lH, 'dd, J = 2.4 , 9.8 Hz, CH = CH2), 6.50 (1H, dd, J = 2.4, 16.6 Hz, CH = CH2), 6.59 (1H, dd, J = 9.8 16.6 Hz, CH = CH2), 7.10 (1H, d, J = 8.3 Hz, Ar-H), 7.19 (1H, d, J = 8.3 Hz, Ar-H), 7.27 (1H, d, J = 8.3, Ar-H), 7.29 (1H, d, J = 8.3 Hz, Ar-H), 7.34 (1H, d, J = 7.8 Hz, Ar-H), 7.36 (1H, d, J = 6.8 Hz, Ar-H), 7.57 (1H, d, J = 7.8 Hz, Ar-H), 7.62 (1H, d, J = 7.8 Hz, Ar-H). It was dissolved in chloroform / methanol (4: 1), 800 mg (2.26 mmol) of the conjugated ketone compound 228 and 425.4 mg (2.48 mmol, 1.1 molar equivalent) of (R) - (+) -1- (1-naphthyl) ) ethylamine and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2266 (981.5 mg, 82.8 %). MS m / z: 524. NMR with ^ -H 6: 1.52 (3H, d, J = 6.6 Hz, CH3), 2.57-2.64 (2H, m, CH2), 2.86-2.97 (2H, m, CH2), 4.41 (2H, d, J = 23.9 Hz, CH2), 4.59 (2H, d, J = 24.9 Hz, CH2), 4.67 (1H, c, J = 6.6 Hz, CH), 7.04 (1H, d, J = 8.3 Hz, Ar-H), 7.13 (1H, d, J = 8.3 Hz, Ar-H), 7.21 (1H, d, J = 8.3 Hz, Ar-H), 7.26-7.31 (3H, m, Ar-H), 7.44-7.51 (3H, m, Ar-H), 7.55 (1H, d, J = 8.1 Hz, Ar-H), 7.59 (1H, d, J = 8.1 Hz, Ar-H), 7.67 (1H, dd, J = 3.0, 6.6 Hz, Ar-H), 7.74 (1H, d, J = 8.1 Hz, Ar-H), 7.87 (1H, dd, J = 2.0 Hz, 8.1, Ar-H), 8.17 (1H, d, J = 8.1 Hz, Ar-H).

EXAMPLE 108 SYNTHESIS OF K-2267 (N '- (4-CHLOROBENCIL) -N' - (3,4-DICHLOROBENCIL) -3-f [(IR) -1- (1-NAFTHYL) ETHYL] AMIN?) PROPANAMIDE) Methanol was dissolved in 1 g (7.06 mmol) of 4-chlorobenzylamine and 1.36 g (7.77 mmol, 1.1 molar equivalent) of 3,4-dichlorobenzaldehyde, and 1.02 g (8.47 mmol, 1.2 molar equivalents) of magnesium sulfate were added. and 10 drops of AcOH. The mixture obtained was then stirred at room temperature for 2 hours. After the reaction was completed, 334.0 mg (8.83 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture while cooling with ice. The mixture obtained was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. The residue obtained was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 1.6777 g (79.2%) of a colorless oil 229. MS m / z: 279. NMR with H 6: 3.72 (2H , s, CH2), 3.73 (2H, s, CH2), 7.15 (1H, dd, J = 2.0, 8.1 Hz, Ar-H), 7.24 (2H, d, J = 8.8 Hz, Ar-H), 7.29 (2H, d, J = 8.8 Hz, Ar-H), 7.38 (1H, d, J = 8.1 Hz, Ar-H), 7.43 (1H, d, J = 2.O Hz, Ar-H). 800 mg (2.66 mmol) of the dibenzylamine compound 229 and 0.45 ml (3.19 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform and added to it, while was cooled with ice, 265 mg (2.93 mmoles, 1.1 molar equivalent) of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 30 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. HE washed with water the chloroform layer and with an aqueous solution W saturated with sodium chloride, and dried over sodium sulfate.

After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 768.9 mg (81.4%) of a colorless oil 230. MS m / z: 333. NMR with 1H §: 4.47 (2H, d, J = 13.4 Hz, CH2), 4.57 (2H, d, J = 13.9 Hz, CH2), 5.79 (1H , dd, J = 3.2, 9.0 Hz, CH = CH2), 6.50 (1H, dd, J = 3.2, 16.6 Hz, CH = CH2), 6.57 (1H, dd, J = 9.0 16.6 Hz, CH = CH2), 7.08-7.46 (7H, m, Ar-H). 20 600 mg (1.69 mmol) of the conjugated ketone compound 230 and 347.2 mg, 2.03 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol was dissolved. (4: 1) and allowed to stand at room temperature for 1 week. After the reaction was completed it was removed by The solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil K-2267 (721.3 mg, 81.1%). MS m / z: 504. NMR with ^ -HS: 1.51 (3H, d, J = 6.6 Hz, CH3), 2.55- 2.62 (2H, m, CH2), 2.84-2.97 (2H, m, CH2), 4.35 (2H, d, J = 18.3 Hz, CH2), 4.52 (2H, d, J = 12.9 Hz, CH2), 4.66 (1H, c, J = 6.6 Hz, CH), 7.04 (2H, d, J = 8.3 Hz, Ar-H), 7.13 (1H, d, J = 8.3 Hz, Ar-H), 7.27-7.29 (1H, m, Ar-H), 7.31 ( 1H, d, J = 8.3 Hz, Ar-H), 7.36 (1H, d, J = 8.1 Hz, Ar-H), 7.39 (1H, d, J = 8.1 Hz, Ar-H), 7.45-7.50 (3H, m Ar-H), 7.66 (1H, d, J = 7.1 Hz, Ar-H), 7.74 (1H, d, J = 8.3 Hz, Ar-H), 7.87 (1H, dd, J = 2.2, 8.3 Hz, Ar-H), 8.17 (1H, d, J = 7.1 Hz, Ar-H).

EXAMPLE 109 S NTESIS OF K-2270 (N ', N' -D (4-METOX BENC L) -3 - [(IR) -1- (1-NAFTHYL) ETHYL AMINO> PROPANAMIDE) To 0.447 ml (3.67 mmoles) of 4-anisaldehyde and 0.479 ml (3.67 mmoles, 1.0 molar equivalent) of 4-methoxybenzylamine, 1.30 ml (4.40 mmoles, 1.2 molar equivalents) of titanium tetraisopropoxide were added and the mixture thus obtained was stirred at room temperature, for 10 hours. After the reaction was complete, the reaction mixture was dissolved in ethanol and 555 mg (14.68 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 231 (762.7 mg, 80.9%). MS m / z: 257. NMR with XH ß: 3.73 (4H, s, CH2), 3.80 (6H, S, OCH3), 6.86 (4H, d, J = 8.5 Hz, Ar-H), 7.25 (4H, d, J = 8.5 Hz, Ar-H). 500 mg (1.95 mmoles) of dibenzylamine compound 231 and 0.33 ml (2.33 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 195 mg (2.15 mmoles, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 232 (602.8 mg 99.4%). MS m / z: 311. NMR with H 6: 3.80 (3H, s, 0CH3), 3.81 (3H, s, OCH3), 4.43 (2H, s, CH2), 4.56 (2H, d, CH2), 5.73 ( 1H, dd, J = 2.2, 10.2 Hz, CH = CH2), 6.48 (1H, dd, J = 2.2, 16.6 Hz, CH = CH2), 6.62 (1H, dd, J = 10.2, 16.6 Hz, CH = CH2 ), 6.85 (2H, d, J = 8.5 Hz, Ar-H), 6.88 (3H, d, J = 8.5 Hz, Ar-H), 7.08 (2H, d, J = 8.5, Ar-H), 7.19 (1H, d, J = 8.5 Hz, Ar-H). It was dissolved in chloroform / methanol (4: 1), 450 mg (1.45 mmol) of the conjugated ketone compound 232 and 297 mg (1.74 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ) ethylamine and allowed to stand at room temperature for 2 weeks. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2270 (366.9 mg, 52.5 %). Subsequently, 244.5 mg (0.51 mmol) of K-2270 obtained in a 10% solution of hydrochloric acid / methanol was dissolved and stirred for 10 minutes. It was then concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to thereby give 150.7 mg (57.3%) of the K-2270 hydrochloride as colorless crystals. MS m / z: 482. NMR with 1H 6: 1.58 (3H, d, J = 6.6 Hz, CH3), 2.63-2.75 (2H, m, CH2), 2.86-2.98 (2H, m, CH2), 3.79 ( 3H, s, 0CH3), 3.80 (3H, s, OCH3), 4.32 (2H, s, CH2), 4.48 (1H, d, J = 14.5 Hz, CH2), 4.55 (1H, d, J = 14.5 Hz, CH2), 4.75 (1H, c, J = 6.6 Hz, CH), 6.83 (2H, d, J = 8.8 Hz, Ar-H), 6.86 (2H, d, J = 8.6 Hz, Ar-H), 7.03 (2H, d, J = 8.5 Hz, Ar-H), 7.14 (2H, d, J = 8.5 Hz, Ar-H), 7. 46-7.53 (3H, m, Ar-H), 7.74 (1H, d, J = 7.8 Hz, Ar-H), 7.76 (1H, d, J = 8.8 Hz, Ar-H), 7.88 (1H, d, J = 7.6 Hz, Ar-H), 8.15 (1H, d, J = 8.1 Hz, Ar-H).

EXAMPLE 110 SYNTHESIS OF K-2272 (N '- (3, 4-DICHLOROBENCIL) -N' - [4- (TRIFLUOROMETOXY) BENCIL] -3- { [(LR) -l- (l- NAFTIL) ETHYL] AMIN ?.}. PROPANAMIDA) Methanol was dissolved in 0.379 ml (2.84 mmol) of 3,4-dichlorobenzylamine and 503 mg (3.56 mmol, 1.0 molar equivalent) of 4- (trifluoromethoxy) benzaldehyde, and 410.2 mg (3.41 mmol, 1.2 molar equivalent) was added to it. magnesium sulfate and 10 drops of AcOH. The mixture obtained was then stirred at room temperature for 30 minutes. After the reaction was completed, 134 mg (3.55 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 10 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, hexane: ethyl acetate (9: 1-4: 1)] to thereby give 777.3 mg (78.2%) of a colorless oil 229. MS m / z: 350. NMR with 1H 6: 3.76 (2H, s, CH2), 3.79 (2H, s, CH2), 7.18 (1H, dd, J = 2.0, 8.5 Hz, Ar-H), 7.18 (2H, d, J = 8.5 Hz, Ar-H), 7.18 (2H, d, J = 8.5 Hz, Ar-H), 7.36 (2H, d, J = 8.5 Hz, Ar-H), 7.39 (1H, d, J = 8.5 Hz, Ar-H), 7.46 (1H, d, J = 2.0 Hz, Ar-H). 500 mg (1.43 mmoles) of the dibenzylamine compound 233 and 0.238 ml (1.71 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 142 mg (1.57 mmoles, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 30 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 454.6 mg (78.7%) of a colorless oil 234. MS m / z: 404 NMR with 1H 6: 4.50 (2H, d, J = 19.0 Hz, CH2), 4.61 (2H, d, J = 21.7 Hz, CH2), 5.80 (1H, dd, J = 1.7, 9.5 Hz, CH = CH2 ), 6.53 (1H, d, J = 1.7, 16.6 Hz, CH = CH2), 6.58 (1H, d, J = 9.5 16.6 Hz, CH = CH2), 7.16-7.22 (5H, m, Ar-H), 7.32 (1H, s, Ar-H), 7.41 (1H, d, J = 8.3 Hz, Ar-H). 350 mg (0.87 mmol) of the conjugated ketone compound 234 and 178 mg, 1.04 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) was dissolved. ) and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil K-2272 (360.7 mg, 72.4% ). Subsequently, 250 mg (0.435 mmol) of K-2272 obtained was dissolved in a 10% solution of hydrochloric acid / methanol and stirred for 10 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to thereby give 230.2 mg (86.5%) of K-2270 hydrochloride as colorless crystals. MS m / z: 575. NMR with 1H 6: 1.60 (3H, d, J = 6.6 Hz, CH3), 2.60-2.76 (2H, m, CH2), 2.88-3.02 (2H, m, CH2), 4.37 ( 2H, d, J = 22.7 Hz, CH2), 4.51 (1H, d, J = 2.4 Hz, CH2), 4.57 (1H, d, J = 6.1 Hz, CH2), 4.72-4.82 (1H, m, CH) , 7.13 (1H, d, J = 8.8 Hz, Ar-H), 7.15 (1H, d, J = 7.3 Hz, Ar-H), 7.17 (1H, d, J = 6.8 Hz, Ar-H), 7.19 (1H, d, J = 8.8 Hz, Ar-H), 7.22 (1H, d, J = 8.8 Hz, Ar-H), 7.28 (1H, d, J = 2.0 Hz, Ar-H), 7.37 (1H , d, J = 8.3 Hz, Ar-H), 7.38 (1H, dd, J = 8.3, 9.3 Hz, Ar-H), 7.47-7.55 (3H, m, Ar-H), 7.72 (1H, d, J = 7.1 Hz, Ar-H), 7.77 (1H, d, J = 8.1 Hz, Ar-H), 7.88 (1H, dd, J = 2.0, 7.8 Hz, Ar-H), 8.14 (1H, d, J = 7.8 Hz, Ar-H).

EXAMPLE 111 SYNTHESIS OF K-2283 (N '- (4-CHLOROBENCIL) -N' - [4- (TRIFLUOROMETOXY) BENCIL] -3-f [(lR) -l- (l-NAFTHYL) ETHYL] AMIN?) PROPANAMIDA) 0.555 ml (3.88 mmol, 1.1 molar equivalent) of 4- (trifluoromethoxy) benzaldehyde and 0.430 ml (4.24 mmol, 1.2 molar equivalent) of 4-chlorobenzylamine was dissolved in methanol, and 509.89 mg (4.24 mmol, 1.2 molar equivalent) was added. ) of magnesium sulfate and 3 drops of AcOH. The mixture obtained was then stirred at room temperature for 10 minutes. After the reaction was completed, 167 mg (4.41 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 10 minutes. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, hexane: ethyl acetate (9: 1-4: 1)] to thereby give 1.092 g (98.1%) of a colorless oil 235. MS m / z: 315. NMR with XH 6: 3.77 (2H, s, CH2), 3.79 (2H, s, CH2), 7.18 (2H, d, J = 7.8 Hz, Ar-H), 7.29 (4H, d, J = 2.2 Hz, Ar-H), 7.37 (2H, d, J = 8.9 Hz, Ar-H). 500 mg (1.58 mmoles) of the dibenzylamine compound 235 and 0.265 ml (1.90 mmoles, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 158 mg (1.74 mmoles, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 40 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 521.3 mg (89.3%) of a colorless oil 236. MS m / z: 369 NMR with §: 4.50 (2H, d, J = 4.9 Hz, CH2), 4.61 (2H, d, J = 8.1 Hz, CH2), 5.78 (1H, dd, J = 2.7, 9.5 Hz, CH = CH2) , 6.50 (1H, dd, J = 2.7, 16.6 Hz, CH = CH2), 6.57 (1H, dd, J = 9.5 16.6 Hz, CH = CH2), 7.09 (1H, d, J = 8.3 Hz, Ar-H ), 7.15-7.21 (4H, m, Ar-H), 7.27 (1H, d, J = 8.1 Hz, Ar-H), 7.28 (1H, d, J = 8.1 Hz, Ar-H), 7.33 (1H , d, J = 8.1 Hz, Ar-H). 400 mg (1.08 mmol) of the conjugated ketone compound 236 and 222 mg, 1.30 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) was dissolved. ) and allowed to stand at room temperature for 8 days. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil K-2283 (452.0 mg, 77.4% ). Subsequently, 248.9 mg (0.46 mmol) of K-2283 obtained was dissolved in a 10% solution of hydrochloric acid / methanol and stirred for 15 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to thereby give 235.0 mg (88.5%) of K-2283 hydrochloride as colorless crystals. MS m / z: 540. NMR with 1H 6: 1.60 (3H, d, J = 6.3 Hz, CH3), 2.62-2.74 (2H, m, CH2), 2.87-2.99 (2H, m, CH2), 4.38 ( 2H, d, J = 4.9 Hz, CH2), 4.55 (2H, t, J = 8.3 Hz, CH2), 4.75-4.80 (1H, m, CH), 7.04 (1H, d, J = 8.5 Hz, Ar- H), 7.12 (1H, d, J = 8.5 Hz, Ar-H), 7.14 (1H, d, J = 8.5 Hz, Ar-H), 7.22 (1H, d, J = 8.5 Hz, Ar-H) , 7.27 (2H, d, J = 8.5 Hz, Ar-H), 7.30 (1H, d, J = 8.5 Hz, Ar-H), 7.45-7.53 (3H, m, Ar-H), 7.72 (1H, d, J = 7.1 Hz, Ar-H), 7.77 (1H, d, J = 8.1 Hz, Ar-H), 7.88 (1H, dd, J = 2.0, 7.3 Hz, Ar-H), 8.14 (1H, d, J = 7.8 Hz, Ar-H).

EXAMPLE 112 SYNTHESIS OF K-2289 (N '- (4-CHLOROBENCIL) -N' - (4-METOXIBENCIL) -3 - { [(IR) -1- (l-NAFTIL) ETHYL] AMIN ?.}. PROPANAMIDA) Methanol 564 mg (4.01 mmol) was dissolved, 1.1 molar equivalent) of 4-chlorobenzaldehyde and 476 mg (3.64 mmol) of 4-methoxybenzylamine, and added 525.8 mg (4.37 mmol, 1.2 molar equivalents) of magnesium sulfate and 5 drops of AcOH. The mixture obtained was then stirred at room temperature for 40 minutes. After the reaction was completed, 172 mg (4.55 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 15 minutes. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, hexane: ethyl acetate (9: 1-4: 1)] to thereby give 711.8 mg (74.8%) of a colorless oil 235. MS m / z: 261. NMR with H d: 3.72 (2H, s, CH2), 3.75 (2H, s, CH2), 3.80 (3H, s, CH2), 6.86 (2H, d, J = 8.5 Hz, Ar- H), 7.24 (2H, d, J = 8.5 Hz, Ar-H), 7.28 (4H, d, J = 2.2 Hz, Ar-H). 501.4 mg (1.92 mmol) of the dibenzylamine compound 237 and 0.32 ml (2.30 mmol, 1.2 molar equivalents) of triethylamine was dissolved in chloroform, and 191 mg (2.11 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 30 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 557.2 mg (91.9%) of a colorless oil 238. MS m / z: 315 NMR with H t): 3.80 (3H, d, J = 5.4 Hz, OCH3), 4. 44 (2H, d, J = 8.5 Hz, CH2), 4.57 (2H, d, J = 4.1 Hz, CH2), 5.75 (1H, dd, J = 1.7, 10.3 Hz, CH = CH2), 6.48 (1H, dd, J = 1.7, 16.6 Hz, CH = CH2), 6.64 (1H, dd, J = 10.3, 16.6 Hz, CH = CH2), 6.85 (1H, d, J = 8.3 Hz, Ar-H), 6.88 (1H, d, J = 8.5 Hz, Ar-H), 7.07 (1H, d, J = 8.3 Hz, Ar-H), 7.08 (1H, d, J = 6.3 Hz, Ar-H), 7.17 (1H, d, J = 8.8 Hz, Ar-H), 7.19 (1H, d, J = 8.3 Hz, Ar-H), 7.28 (1H, d, J = 8.5 Hz, Ar-H), 7.32 (2H, d, J = 7.8 Hz, Ar- H) ,. 414 mg (1.31 mmol) of the conjugated ketone compound 238 and 270 mg, 1.57 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) was dissolved. ) and allowed to stand at room temperature for 12 days. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil K-2289 (441.8 mg, 69.3% ). Subsequently, 269.4 mg (0.55 mmol) of K-2289 obtained was dissolved in a 10% solution of hydrochloric acid / methanol and stirred for 15 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to thereby give 270.1 mg (93.2%) of K-2289 hydrochloride as colorless crystals. MS m / z: 486. NMR with H 6: 1.56 (3H, d, J = 6.6 Hz, CH3), 2.57-2.70 (2H, m, CH2), 2.84-2.95 (2H, m, CH2), 3.80 ( 3H, d, J = 2.2 Hz, OCH3), 4.33 (2H, d, J = 5.4 Hz, CH2), 4.52 (2H, t, J = 6.6 Hz, CH2), 4.70-4.74 (1H, m, CH) , 6.83 (1H, d, J = 9.0 Hz, Ar-H), 6.85 (1H, d, J = 9.0 Hz, Ar-H), 7.02 (1H, d, J = 8.5 Hz, Ar-H), 7.03 (1H, d, J = 8.5 Hz, Ar-H), 7.12 (1H, d, J = 8.5 Hz, Ar-H), 7.13 (1H, d, J = 8.3 Hz, Ar-H), 7.27 (1H , d, J = 8.5 Hz, Ar-H), 7.29 (1H, d, J = 8.5 Hz, Ar-H), 7.46-7.52 (3H, m, Ar-H), 7.71 (1H, dd, J = 3.4, 6.8 Hz, Ar-H), 7.75 (1H, d, J = 8.3 Hz, Ar-H), 7.87 (1H, d, J = 7.6 Hz, Ar-H), 8.15 (1H, d, J = 7.6 Hz, Ar-H).

EXAMPLE 113 SYNTHESIS OF K-2290 (N '- (4-METOXYBENCIL) -N' - [4- (TRIFLUOROMETHYL) BENCIL] -3 - f [(lR) -l- (l- NAFTIL) ETHYL] AMINO PROPANAMIDE) 1,269 g (7.29 mmoles) of 4- (trifluoromethyl) benzaldehyde and 1 g (7.29 mmoles) of 4-methoxybenzylamine were dissolved in methanol, and 1.0530 g (8.75 mmoles, 1.2 molar equivalents) of magnesium sulfate and 10 g of methanol were added thereto. AcOH drops. The mixture obtained was then stirred at room temperature for 2 hours. After the reaction was completed, 344.7 mg (9.11 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. The residue obtained was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 1.40 g (65.0%), of a colorless oil 239. MS m / z: 295. NMR with 1H 6: 3.73 (2H, s, CH2), 3.80 (3H, s, OCH3), 3.83 (2H, s, CH2), 6.87 (2H, d, J = 8.5 Hz, Ar-H), 7.24 (2H, d, J = 8.5 Hz , Ar-H), 7.45 (2H, d, J = 8.5 Hz, Ar-H), 7.57 (1H, d, J = 87.5 Hz, Ar-H), 7.59 (1H, d, J = 8.5 Hz, Ar -H) 1.30 g (4.40 mmol) of the dibenzylamine compound 239 and 0.74 ml (5.28 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 438.3 mg (4.84 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 30 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 974.7 mg (63.5%) of a colorless oil 240. MS m / z: 349 NMR with 1H 6: 3.80 (3H, d, J = 4.9 Hz, 0CH3), 4.53 (2H, d, J = 52.0 Hz, CH2), 4.61 (2H, d, J = 45.1 Hz, CH2), 5.77 ( 1H, dd, J = 2.0, 10.5 Hz, CH = CH2), 6.49 (1H, dd, J = 2.0, 16.6 Hz, CH = CH2), 6.65 (1H, dd, J = 10.5, 16.6 Hz, CH = CH2 ), 6.85 (1H, d, J = 8.3 Hz, Ar-H), 6.89 (1H, d, J = 8.5 Hz, Ar-H), 7.07 (1H, d, J = 8.3 Hz, Ar-H), 7.17 (1H, d, J = 8.1 Hz, Ar-H), 7.27 (1H, d, J = 6.8 Hz, Ar-H), 7.35 (1H, d, J = 7.8 Hz, Ar-H), 7.56 ( 2H, d, J = 8.1 Hz, Ar-H), 7.61 (1H, d, J = 7.3 Hz, Ar-H). 874.7 mg (2.50 mmol) of the conjugated ketone compound 240 and 513.9 mg, 3.00 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) was dissolved. ) and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil K-2290 (1,005 g, 77.2% ). MS m / z: 520. NMR with H §: 1.51 (3H, dd, J = 3.0, 6.6 Hz, CH3), 2. 55 (1H, t, J = 6.1 Hz, CH2), 2.67 (1H, t, J = 6.1 Hz, CH2), 2.82-2.98 (2H, m, CH2), 3.79 (3H, d, J = 4.6 Hz, OCH3), 4.39 (2H, d, J = 28.3 Hz, CH2), 4.57 (2H, d, J = 30.0 Hz, CH2), 4.64-4.70 (1H, m, CH), 6.83 (1H, d, J = 8.8 Hz, Ar-H), 6.86 (1H, d, J = 8.8 Hz, Ar-H), 7.03 (1H, d, J = 8.8 Hz, Ar-H), 7.12 (1H, d, J = 8.6 Hz, Ar-H), 7.21 (1H, d, J = 8.1 Hz, Ar-H), 7.30 (1H, d, J = 8.3 Hz, Ar-H), 7.43-7.51 (3H, m, Ar-H), 7.54 (1H, d, J = 8.3 Hz, Ar-H), 7.57 (1H, d, J = 8.1 Hz, Ar-H), 7.68 (1H, t, J = 7.6 Hz, Ar-H), 7.73 (1H, dd, J = 3.7, 8.1 Hz, Ar-H), 7.86 (1H, dd, J = 2.4, 7.3 Hz, Ar-H), 8.17 (1H, d, J = 7.6 Hz, Ar-H) .

EXAMPLE 114 SYNTHESIS OF K-2291 (N1 - (4-CHLOROBENCIL) -N '- (2-NAFETYMETIL) -3- { [(IR) -1- (1-NAFTHYL) ETHYL] AMINO> PROPANAMIDE) To 500 mg (3.20 mmoles) of 2-naphthaldehyde and 0.389 ml (3.20 mmoles, 1.0 molar equivalent) of 4-chlorobenzylamine, 1.70 ml (5.76 mmoles, 1.8 molar equivalents) of titanium isopropoxide was added and the mixture thus obtained was stirred at room temperature, for 4 hours. After the reaction was completed, the reaction mixture was dissolved in ethanol and 485 mg (12.82 mmol, 4.0 molar equivalent) of sodium borohydride was added thereto. The mixture thus obtained was then stirred at room temperature for 29 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. Ethyl acetate and water were added to the obtained residue and the mixture was filtered through celite. The residue was washed with ethyl acetate and the wash liquor was combined with the filtrate and extracted with ethyl acetate. The ethyl acetate layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The oil obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil 241 (767.4 mg, 85.2%). MS m / z: 281. NMR with XH: d: 3.80 (2H, s, CH2), 3.95 (2H, s, CH2), 7.26 (2H, d, J = 12.0 Hz, Ar-H), 7.31 (2H, d, J = 12.0 Hz, Ar-H), 7.42-7.49 (3H, m, Ar-H), 7.75 ( 1H, s, Ar-H), 7.81 (1H, d, J = 8.1 Hz, Ar-H), 7.82 (1H, d, J = 8.5 Hz, Ar-H), 7.83 (1H, d, J = 8.1 Hz, Ar-H). 506.7 mg (1.80 mmol) of the dibenzylamine compound 241 and 0.301 ml (2.16 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform and 179 mg (1.98 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and saturated aqueous sodium chloride solution were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give an oil 242 (652.4 mg 100%). MS m / z: 335. NMR with XH 6: 4.58 (2H, d, J = 65.9 Hz, CH2), 4.74 (2H, d, J = 52.0 Hz, CH2), 5.76 (1H, dd, J = 2.0, 10.2 Hz, CH = CH2), 6.53 (1H, dd, J = 2.0, 16.6 Hz, CH = CH2), 6.54 (1H, dd, J = 10.2 16.6 Hz, CH = CH2), 7.10 (1H, d, J = 8.1 Hz, Ar-H), 7.21-7.35 (4H, m, Ar-H), 7.437-7.62 (3H, m, Ar-H), 7.79-7.86 (3H, m, Ar-H). It was dissolved in chloroform / methanol (4: 1), 500 mg (1.49 mmol) of the conjugated ketone compound 242 and 307 mg (1798 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ) ethylamine and allowed to stand at room temperature for 13 days. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil, K-2291 (521.1 mg, 69.0%). Subsequently, 521.1 g (69.0%) was dissolved. Subsequently, 394.1 mg (0.78 mmol) of K-2291 obtained in a 10% solution of hydrochloric acid / methanol was dissolved and stirred for 15 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to give 358.7 mg (85.1%) of K-2291 hydrochloride, as colorless crystals. MS m / z: 506. NMR with H 6: 1.56 (3H, d, J = 6.8 Hz, CH3), 2.61-2.76 (2H, m, CH2), 2.88-3.01 (2H, m, CH2), 4.38 ( 1H, s, CH2), 4.55 (1H, s, CH2), 4.62 (1H, d, J = 3.7 Hz, CH2), 4.75 (1H, d, J = 6.8 Hz, CH2), 4.70-4.76 (1H, m, CH), 7.05 (1H, d, J = 8.5 Hz, Ar-H), 7.16 (1H, d, J = 8.3 Hz, Ar-H), 7.28 (1H, d, J = 8.5 Hz, Ar- H), 7.30 (1H, d, J = 8.5 Hz, Ar-H), 7.44-7.58 (6H, m, Ar-H), 7.69-7.89 (7H, m, Ar-H), 8.10-8.17 (1H , m, Ar-H).

EXAMPLE 115 SYNTHESIS OF K-2294 (N '- (3, 4-DICHLOROBENCIL) -N' - (4-METHYLBENCIL) -3-f [(IR) -1- (l-NAFTHYL) ETHYL] AMINO> PROPANAMIDE ) Methanol was dissolved in 1555 g (8.25 mmoles) of 3,4-dichlorobenzaldehyde and 1 g (8.25 mmoles, 1.0 molar equivalent) of 4-methylbenzylamine, and 1.1920 g (9.90 mmoles, 1.2 molar equivalents) of magnesium sulfate was added. and 10 drops of AcOH. The mixture obtained was then stirred at room temperature for 2 hours. After the reaction was completed, 390.2 mg (10.30 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. The residue obtained was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 1.5942 g (69.2%), of a colorless oil 243. MS m / z: 280. NMR with H 6: 2.34 (3H , s, CH3), 3.73 (4H, s, CH2x2), 7.14 (2H, d, J = 8.1 Hz, Ar-H), 7.16 (1H, dd, J = 2.0, 8.1 Hz, Ar-H), 7.19 (2H, d, J = 8.1 Hz, Ar-H), 7.37 (1H, d, J = 8.1 Hz, Ar-H), 7.43 (1H, d, J = 2.0 Hz, Ar-H). 1.4942 g (5.35 mmol) of the dibenzylamine compound 243 and 0.89 ml (6.42 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 532.6 mg (5.88 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 30 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 1.6587 g (92.9%) of a colorless oil 244. MS m / z: 334 NMR with H 6: 2.34 (3H, d, J = 6.3 Hz, OCH3), 4.46 (2H, d, J = 13.4 Hz, CH2), '4.58 (2H, d, J = 16.1 Hz, CH2), 5.76 (1H, dd, J = 2.0, 10.2 Hz, CH = CH2), 6.48 (1H, dd, J = 2.0, 16.8 Hz, CH = CH2), 6.63 (1H, dd, J = 10.2, 16.8 Hz, CH = CH2), 7.04 (2H, d, J = 7.8 Hz, Ar-H), 7.09 (1H, d, J = 8.3 Hz, Ar-H), 7.17 (2H, d, J = 7.8 Hz, Ar-H) , 7.31 (1H, s, Ar-H), 7.37 (1H, d, J = 8.3 Hz, Ar-H). 1.5587 g (4.67 mmol) of the conjugated ketone compound 244 and 959.6 mg, 5.60 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) was dissolved. ) and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil K-2294 (2.1115 g, 89.3% ). MS m / z: 505. NMR with H? : 1.50 (3H, d, J = 6.6 Hz, CH3), 2.34 (3H, d, J = 6.6 Hz, CH3), 2.52 (1H, dt, J = 3.4, 9.3 Hz, CH2), 2.63 (1H, t , J = 6.6 Hz, CH3), 2.74-2.96 (2H, m, CH2), 4.35 (2H, d, J = 22.0 Hz, CH2), 4.53 (2H, d, J = 13.7 Hz, CH2), 4.62- 4.68 (1H, m, CH), 6.99 (1H, d, J = 7.8 Hz, Ar-H), 7.04 (1H, dd, J = 2.0, 8. 1 Hz, Ar-H), 7.09 (1H, d, J = 8.3 Hz, Ar-H), 7.12 (1H, d, J = 8.1 Hz, Ar-H), 7.14 (1H, d, J = 8.1 Hz, Ar-H), 7.26 (1H, d, J = 2.0 Hz, Ar-H), 7.34 (1H, d, J = 8.3 Ar- H), 7.43-7.52 (3H, m, Ar-H), 7.68 (1H, d, J = 7.1 Hz, Ar-H), 7.72 (1H, d, J = 8.1 Hz, Ar-H), 7.85 ( 1H, d, J = 7.1 Hz, Ar-H), 8.17 (1H, d, J = 7.1 Hz, Ar-H).

EXAMPLE 116 SYNTHESIS OF K-2299 (N '- (4-METHYLBENCIL) -N' - [4- (TRIFLUOROMETHYL) BENCIL] 3 - T [(IR) -1- (1-NAFTHYL) ETHYL] AMIN?) PROPANAMIDE ) Methanol was 1.4369 g (8.25 mmoles) of 4- (trifluoromethyl) benzaldehyde and 1 g (8.25 mmoles), 1.0 molar equivalent) of 4-methylbenzylamine, and 1.1920 g (9.90 mmol, 1.2 molar equivalents) of magnesium sulfate and 10 drops of AcOH were added. The mixture obtained was then stirred at room temperature for 2 hours. After the reaction was completed, 390.2 mg (10.30 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was distilled off under reduced pressure. The residue obtained was extracted with ethyl acetate. The ethyl acetate layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give 1.6877 g (73.2%) of a colorless oil 245.

MS m / z: 279. NMR with XH 6: 2.34 (3H, s, CH3), 3.76 (2H, s, CH2), 3.85 (2H, s, CH2), 7.14 (2H, d, J = 7.8 Hz, Ar-H), 7.21 (2H, d, J = 8.1 Hz, Ar-H), 7.46 (2H, d, J = 8.1 Hz, Ar-H), 7.57 (2H, d, J = 8.3 Hz, Ar- H). Chloroform 1.5877 g (5.68 mmoles) of dibenzylamine compound 245 and 0.95 ml (6.82 mmoles, 1.2 molar equivalents) of triethylamine was dissolved, and 565.96 mg (6.25 mmoles, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 30 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 1.5568 g (82.0%) of a colorless oil 246. MS m / z: 333 NMR with 1H ß: 2.34 (3H, d, J = 6.8 Hz, CH3), 4.52 (2H, d, J = 26.8 Hz, CH2), 4.65 (2H, d, J = 22.4 Hz, CH2), 5.76 (1H, dd, J = 1.7, 10.2 Hz, CH = CH2), 6.49 (1H, dd, J = 1.7, 16.8 Hz, CH = CH2), 6.64 (1H, dd, J = 10.2, 16.8 Hz, CH = CH2), 7.05 (2H, d, J = 7.8 Hz, Ar-H), 7.17 (2H, d, J = 7.8 Hz, Ar-H), 7.35 (2H, d, J = 8.1 Hz, Ar-H), 7.56 (2H, d, J = 8.1 Hz, Ar-H). 1.4568 g (4.36 mmol) of the conjugated ketone compound 246 and 896.8 mg (5.24 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol was dissolved (4.- 1) and allowed to stand at room temperature for 1 week. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil K-2299 (884.4 mg, 40.1% ). MS m / z: 504. NMR with H 6: 1.51 (3H, d, J = 6.6 Hz, CH3), 2.33 (3H, d, J = 6.3 Hz, CH3), 2.53 (1H, dt, J = 6.1, 19.3 Hz, CH2), 2.66 (1H, t, J = 6.1 Hz, CH3), 2.77-2.97 (2H, m, CH2), 4.40 (2H, d, J = 19.8 Hz, CH2), 4.59 (2H, d , J = 24.9 Hz, CH2), 4.65-4.69 (1H, m, CH), 7.00 (1H, d, J = 7.8 Hz, Ar-H), 7.08 (1H, d, J = 8.3 Hz, Ar-H), 7.12 (1H, d, J = 7.8 Hz, Ar-H), 7.14 (1H, d, J = 7.8 Hz, Ar-H), 7.20 (1H, d, J = 8.1 Hz, Ar-H), 7.30 (1H, d, J = 8.1 Ar-H), 7.43-7.51 (3H, m, Ar-H), 7.53 ( 1H, d, J = 8.3 Hz, Ar-H), 7.57 (1H, d, J = 8.1 Hz, Ar-H), 7.68 (1H, d, J = 6.8 Hz, Ar-H), 7.73 (1H, dd, J = 3.2, 8.1 Hz, Ar-H), 7.86 (1H, dd, J = 2.2, 7.6 Hz, Ar-H), 8.17 (1H, d, J = 7.6 Hz, Ar-H).

EXAMPLE 117 SYNTHESIS OF K-2300 (N ', N' -DI (4-METHYLBENCIL) -3-C [(IR) -1- (1-NAFTHYL) ETHYL] AMIN?) PROPANAMIDE) Methanol was dissolved in 500 mg (3.56 mmoles) of 4-tolualdehyde and 503.6 mg (3.56 mmoles, 1.0 molar equivalent) of 4-methylbenzylamine, and 514.2 mg (4.27 mmoles, 1.2 molar equivalents) of magnesium sulfate and 3 drops of AcOH were added. The mixture obtained was then stirred at room temperature for 50 minutes. After the reaction was completed, 168.3 mg (4.45 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 15 minutes. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, hexane: ethyl acetate (9: 1-4: 1)] to thereby give 819.4 mg (88.2%) of a colorless oil 247. MS m / z: 225. NMR with H ß: 2.33 (6H, s, CH3x2), 3.75 (4H, s, CH2x2), 7.13 (4H, d, J = 7.8 Hz, Ar-H), 7.22 (4H, d, J = 7.8 Hz, Ar-H). 500 mg (2.22 mmoles) of the dibenzylamine compound 247 and 0.372 ml (2.67 mmoles) were dissolved in chloroform., 1.2 molar equivalents) of triethylamine, and 221 mg (2.44 mmoles, 1.1 molar equivalent) of acryloyl chloride, dissolved in chloroform, was added while cooling with ice. The reaction mixture was stirred for 30 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 534.5 mg (86.3%) of a colorless oil 248. MS m / z: 279 NMR with H 6: 2.34 (3H, s, CH3), 2.35 (3H, s, CH3), 4.45 (2H, s, CH2), 4.60 (2H, s, CH2), 5.71 (1H, dd, J = 2.2, 10.2 Hz, CH = CH2), 6.47 (1H, dd, J = 2.2, 16.6 Hz, CH = CH2), 6.60 (1H, dd, J = 10.2, 16.6 Hz, CH = CH2), 7.05 (2H, d, J = 7.8 Hz, Ar-H), 7.13-7.17 (6H, m, Ar-H). 400 mg (1.43 mmol) of the conjugated ketone compound 248 and 295 mg (1.72 mmol, 1.2 molar equivalent) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol was dissolved. (4: 1) and allowed to stand at room temperature for 2 weeks. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil K-2300 (372.5 mg, 57.9% ). Subsequently it dissolved 253. 6 mg (0.56 mmol) of K-2300 obtained in a 10% solution of hydrochloric acid / methanol and stirred for 15 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized in ethanol / water to give in that way 113. 7 mg (41.4%) of the K-2300 hydrochloride, as colorless crystals. MS m / z: 450. NMR with 1H 6: 1.57 (3H, d, J = 6.6 Hz, CH3), 2.34 (3H, s, CH3), 2.60-2.71 (2H, m, CH2), 2.85-2.97 (2H, m, CH2), 4.35 (2H, s, CH2), 4.52 (1H, d, J = 14.6 Hz, CH2), 4.59 (1H, d, CH2), 4.74 (1H, c, J = 6.6 Hz, CH), 7.00 (2H, d, J = 8.1 Hz, Ar-H), 7.11 (4H, d, J = 1.2 Hz, Ar-H), 7.14 (2H, d, J = 7.8 Hz, Ar-H), 7.45-7.52 (3H, m, Ar-H), 7.74 (1H, d, J = 7.8 Hz, Ar- H), 7.75 (1H, d, J = 8.8 Hz, Ar-H), 7.87 (1H, dd, J = 2.2, 7.8 Hz, Ar-H), 8.14 (1H, d, J = 7.8 Hz, Ar-H).

EXAMPLE 118 SYNTHESIS OF K-2309 (N '- (3, 4-DICHLOROBENCIL) -N' - (4-METOXYBENCIL) -3-f [(IR) -1- (1-NAFTHYL) ETHYL] AMINO PROPANAMIDE) 702 mg (4.01 mmol, 1.1 molar equivalents) of 3,4-dichlorobenzaldehyde and 0.476 ml were dissolved in methanol. (3.64 mmol) of 4-methylbenzylamine, and 525.8 mg was added (4.37 mmoles, 1.2 molar equivalents) of magnesium sulfate and 5 drops of AcOH. The mixture obtained was then stirred at room temperature for 30 minutes. After the reaction was completed, 172 mg was added to the reaction mixture. (4.55 mmoles, 1.25 molar equivalents) of sodium borohydride. The mixture obtained was stirred at room temperature for 20 minutes. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, hexane-ethyl acetate (9: 1-4: 1)] to thereby give 827.0 mg (76.8%) of a colorless oil 249. MS m / z: 296. NMR with H d: 3.72 (2H, s, CH2), 3.74 (2H, s, CH2), 3.80 (3H, s, OCH3), 6.87 (2H, d, J = 8.8 Hz, Ar -H), 7.18 (1H, dd, J = 2.0, 8.3 Hz, Ar-H), 7.24 (2H, d, J = 8.3 Hz, Ar-H), 7.38 (1H, d, J = 8.1 Hz, Ar -H), 7.45 (1H, d, J = 2.0 Hz, Ar-H). 711.2 mg (2.41 mmol) of the dibenzylamine compound 249 and 0.402 ml (2.89 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 240 mg (2.65 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 45 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 837.2 mg (99.3%) of a colorless oil 250. MS m / z: 350 .NMR with -H Ü: 3.81 (3H, s, OCH3), 4.50 (2H, d, J = 44.2 Hz, CH2), 4.54 (2H, d, J = 49.3 Hz, CH2), 5.78 (1H, dd , J = 1.7, 10.2 Hz, CH = CH2), 6.59 (1H, dd, J = 1.7, 16.6 Hz, CH = CH2), 6.65 (1H, dd, J = 10.2, 16.6 Hz, CH = CH2), 6.89 (2H, d, J = 8.5 Hz, Ar-H), 7.07 (2H, d, J = 8.5 Hz, Ar-H), 7.09 (1H, d, J = 8.3 Hz, Ar-H), 7.30 (1H , s, Ar-H), 7.38 (1H, d, J = 8.3 Hz, Ar-H). 692.4 mg (1.98 mmol) of the conjugated ketone compound 250 and 407 mg (2.37 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol was dissolved. (4: 1) and allowed to stand at room temperature for 2 weeks. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained [silica gel, chloroform] was purified by column chromatography to thereby give a colorless oil K-2309 (835.9 mg, 81.0% ). Subsequently 630.1 mg (1.21 mmol) of K-2309 obtained in a 10% solution of hydrochloric acid / methanol was dissolved and stirred for 15 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to thereby give 566.8 mg (84.0%) of the K-2309 hydrochloride as colorless crystals. MS m / z: 521. NMR with 1H 6: 1.55 (3H, d, J = 6.3 Hz, CH3), 2.55-2.70 (2H, m, CH2), 2.86-2.97 (2H, m, CH2), 3.80 ( 3H, d, J = 3.4 Hz, 0CH3), 4.33 (2H, d, J = 12.7 Hz, CH2), 4.51 (2H, d, J = 8.8 Hz, CH2), 4.68-4.73 (1H, m, CH) , 6.85 (2H, d, J = 8.8 Hz, Ar-H), 7.02 (2H, d, J = 8.5 Hz, Ar-H), 7.11 (1H, d, J = 8.5 Hz, Ar-H), 7.26 (1H, s, Ar-H), 7.35 (1H, d, J = 8.3 Ar-H), 7.45-7.52 (3H, m, Ar-H), 7.70 (1H, t, J = 6.8 Hz, Ar- H), 7.75 (1H, d, J = 8.3 Hz, Ar-H), 7.87 (1H, dd, J = 2.2, 7.8 Hz, Ar-H), 8.16 (1H, d, J = 7.8 Hz, Ar- H).

EXAMPLE 119 SYNTHESIS OF K-2310 (N '- (4-METHYLBENCIL) -N' - [4- (TRIFLUOROMETOXY) BENCIL] -3 - f [(lR) -l- (l- NAFTIL) ETHYL] AMINO PROPANAMIDE) 0.648 ml (4.54 mmol, 1.1 molar equivalents) of 4- (trifluoromethoxy) benzaldehyde and 0.525 ml (4.13 mmol) of 4-methylbenzylamine were dissolved in methanol, and 596.6 mg (4.96 mmol, 1.2 molar equivalents) of sodium sulfate were added to it. magnesium and 5 drops of AcOH. The mixture obtained was then stirred at room temperature for 40 minutes. After the reaction was completed, 195 mg (5.16 mmol, 1.25 molar equivalents) of was added to the reaction mixture. sodium borohydride. The mixture obtained was stirred at room temperature for 20 minutes. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, hexane: ethyl acetate (9: 1-4: 1)] to thereby give 979.1 mg (80.4%) of a colorless oil 251. MS m / z: 295. NMR with H 6: 2.34 (3H, s, CH3), 3.76 (2H, s, CH2), 3.79 (2H, s, CH2), 7.14 (2H, d, J = 8.1 Hz, Ar- H), 7.16 (2H, d, J = 8.5 Hz, Ar-H), 7.22 (2H, d, J = 8.1 Hz, Ar-H), 7.36 (2H, d, J = 8.5 Hz, Ar-H) . 846.8 mg (2.87 mmol) of the dibenzylamine compound 251 and 0.480 ml (3.44 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 286 mg (3.16 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 45 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 844.5 mg (84.3%) of a colorless oil 252. MS m / z: 349 NMR with H 6: 2.34 (3H, d, J = 6.8 Hz, CH3), 4.55 (2H, d, J = 49.0 Hz, CH2), 4.56 (2H, d, J = 50.2 Hz, CH2), 5.75 ( 1H, dd, J = 2.2, 10.0 Hz, CH = CH2), 6.49 (1H, dd, J = 2.2, 16.8 Hz, CH = CH2), 6.62 (1H, dd, J = 10.0, 16.8 Hz, CH = CH2 ), 7.04 (2H, d, J = 7.8 Hz, Ar-H), 7.13-7.21 (4H, m, Ar-H), 7.28 (2H, d, J = 8.5 Hz, Ar-H). 685.1 mg (1.96 mmol) of conjugated ketone compound 252 and 403 mg (2.36 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) was dissolved. ) and allowed to stand at room temperature for 12 days. After the reaction was completed, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel], chloroform] to thereby give a colorless oil K-2310 (777.8 mg, 76.3%). Subsequently, 539.0 mg (1.04 mmol) of K-2310 obtained in a 10% solution of hydrochloric acid / methanol was dissolved and stirred for 15 minutes. Then it was concentrated under reduced pressure. The crystals thus formed were recrystallized from ethanol / water to thereby give 493.0 mg (85.1%) of the K-2310 hydrochloride as colorless crystals. MS m / z: 520. NMR with H 6: 1.52 (3H, d, J = 6.6 Hz, CH3), 2.34 (3H, d, J = 5.4 Hz, CH3), 2.62 (2H, dt, J = 5.9, 21.7 Hz, CH2), 2. 84-2.96 (2H, m, CH2), 4.38 (2H, s, CH2), 4.56 (2H, d, J = 8.6 Hz, CH2), 4.67 (1H, c, J = 6.6 Hz, CH), 7.00 (2H, d, J = 8.1 Hz, Ar-H), 7.07-7.18 (4H, m, Ar-H), 7.22 ( 2H, d, J = 8.6 Hz, Ar-H), 7.44-7.51 (3H, m, Ar-H), 7.68 (1H, d, J = 6.6 Hz, Ar-H), 7.73 (1H, d, J = 8.1 Hz, Ar-H), 7.86 (1H, dd, J = 2.2, 8.1 Hz, Ar-H), 8.16 (1H, d, J = 8.5 Hz, Ar-H).

EXAMPLE 120 SYNTHESIS OF K-2311 0.573 ml (4.01 mmol, 1.1 molar equivalents) of 4- (trifluoromethoxy) benzaldehyde and 0.476 ml (3.64 mmol) of 4-methylbenzylamine were dissolved in methanol, and 525.8 mg (4.37 mmol, 1.2 molar equivalents) of sodium sulfate were added to it. magnesium and 5 drops of AcOH. The mixture obtained was then stirred at room temperature for 30 minutes. After the reaction was complete, 172 mg (4.55 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 30 minutes. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, hexane: ethyl acetate (9: 1-4: 1)] to thereby give 944.0 mg (83.4%) of a colorless oil 253. MS m / z: 311. NMR with ^ -H 6: 3.74 (2H, s, CH2), 3.79 (2H, s, CH2), 3.80 (2H, s, 0CH3), 6.87 (2H, d, J = 8.5 Hz, Ar-H), 7.17 (2H, d, J = 8.3 Hz, Ar-H), 7.25 (2H, d, J = 8.3 Hz, Ar-H), 7.37 (2H, d, J = 8.5 Hz, Ar- H). 766.5 mg (2.46 mmol) of the dibenzylamine compound 253 and 0.411 ml (2.95 mmol, 1.2 molar equivalents) of triethylamine were dissolved in chloroform, and 245 mg (2.71 mmol, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 45 minutes at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After distilling off the solvent, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 749.0 mg (83.4%) of a colorless oil 254. MS m / z: 365 NMR with 1H 6: 3.80 (3H, s, OCH3), 4.48 (2H, d, J = 13.4 Hz, CH2), 4.60 (2H, d, J = 12.4 Hz, CH2), 5.76 (1H, dd, J = 2.0, 10.2 Hz, CH = CH2), 6.49 (1H, dd, J = 2.0, 16.8 Hz, CH = CH2), 6.65 (1H, dd, J = 10.2, 16.8 Hz, CH = CH2), 6.84 (1H , d, J = 8.5 Hz, Ar-H), 6.88 (1H, d, J = 8.5 Hz, Ar-H), 7.07 (1H, d, J = 8.3 Hz, Ar-H), 7.16 (1H, d , J = 8.8 Hz, Ar-H), 7.18 (3H, d, J = 7.6 Hz, Ar-H), 7.27 (1H, d, J = 9.5 Hz, Ar-H). 612.8 mg (1.68 mmol) of conjugated ketone compound 254 and 345 mg (2.01 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol (4: 1) was dissolved. ) and allowed to stand at room temperature for 12 days. After the reaction was complete, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [silica gel, chloroform] to thereby give a colorless oil K-2311 (668.3 mg, 74.2% ). MS m / z: 536. NMR with HO: 1.53 (3H, d, J = 6.6 Hz, CH3), 2.55-2.73 (2H, m, CH2), 2.84-2.96 (2H, m, CH2), 3.79 ( 3H, d, J = 3.2 Hz, OCH3), 4.36 (2H, d, J = 10.0 Hz, CH2), 4.54 (2H, d, J = 12.9 Hz, CH2), 4.70 (1H, c, J = 6.6 Hz , CH), 6.82 (1H, d, J = 8.8 Hz, Ar-H), 6.85 (1H, d, J = 8.8 Hz, Ar-H), 7.02 (2H, d, J = 8.5 Hz, ArH), 7.12 (1H, d, J = 8.8 Hz, Ar-H), 7.13-7.18 (3H, m, Ar-H), 7.22 (1H, d, J = 8.5 Hz, Ar-H), 7.45-7.51 (3H , m, Ar-H), 7.70 (1H, t, J = 6.6 Hz, Ar-H), 7.74 (1H, d, J = 8.3 Hz, Ar-H), 7.86 (1H, d, J = 8.1 Hz , Ar-H), 8.16 (1H, d, J = 8.1 Hz, Ar-H).

PLE 121 SYNTHESIS OF K-2312 490 mg (4.01 mmol, 1.1 molar equivalents) of 4-hydroxybenzaldehyde and 0.476 ml (3.64 mmol) of 4-methylbenzylamine were dissolved in methanol, and 525.8 mg was added. (4.37 mmoles, 1.2 molar equivalents) of magnesium sulfate and 5 drops of AcOH. The mixture obtained was then stirred at room temperature for 45 minutes. After the reaction was complete, 172 mg (4.55 mmol, 1.25 molar equivalents) of sodium borohydride was added to the reaction mixture. The mixture obtained was stirred at room temperature for 10 minutes. After the reaction was complete, the solvent was distilled off under reduced pressure. The obtained residue was extracted with chloroform. The chloroform layer was washed with a saturated aqueous solution of sodium bicarbonate, with water and with a saturated aqueous solution of sodium chloride, and dried over sodium sulfate and the solvent was distilled off under reduced pressure. The oil thus obtained was purified by column chromatography [silica gel, chloroform / methanol] to thereby give 858.9 mg (97.1%) of a colorless oil 255. MS m / z: 243. NMR with 1H 6: 3.69 (2H, s, CH2), 3.77 (2H, s, CH2), 3.79 (2H, s, 0CH3), 6.64 (2H, d, J = 8.5 Hz, Ar-H), 6.86 (2H, d, J = 8.8 Hz, Ar-H), 7.09 (2H, d, J = 8.5 Hz, Ar-H), 7.26 (2H, d, J = 8.5 Hz, Ar-H). Chloroform 521.4 mg (2.15 mmoles) of dibenzylamine compound 255 and 0.359 ml (2.57 mmoles, 1.2 molar equivalents) of triethylamine was dissolved, and 214 mg (2.36 mmoles, 1.1 molar equivalent) was added while cooling with ice. of acryloyl chloride, dissolved in chloroform. The reaction mixture was stirred for 1 hour at room temperature. After the reaction was complete, the reaction mixture was poured into water and extracted with chloroform. The chloroform layer and a saturated aqueous solution of sodium chloride were washed with water and dried over sodium sulfate. After the solvent was distilled off, the oil thus obtained was purified by means of column chromatography [silica gel, chloroform] to thereby give 375.5 mg (58.8%) of a colorless oil 256. A MS m / z: 297. NMR with 1H 6: 3.80 (3H, d, J = 6.8 Hz, 0CH3), 4.44 (2H, d, J = 16.1 Hz, CH2), 4.56 (2H, d, J = 9.0 Hz, CH2), 5.76 (1H, dd, J = 2.2, 10.2 Hz, CH = CH2), 6.48 (1H, ddd, J = 2.0, 7.1, 16.6 Hz, CH = CH2), 6.64 (1H, ddd, J = 3.2, 10.2, 16.6 Hz, CH = CH2), 6.79 (1H, d, J = 8.5 Hz, Ar-H), 6.83 (1H, d, J = 8.5 Hz, Ar-H), 6.85 (1H, d, J = 8.5 Hz, Ar-H), 6.89 (1H, d, J = 8.5 Hz, Ar-H), 6.98 (1H, d, J = 8.3 Hz, Ar-H), 7.08 (1H, d, J = 6.8 Hz, Ar-H), 7.10 (1H, d, J = 6.8 Hz, Ar-H), 7.19 (1H, d, J = 8.5 Hz, Ar-H). ^ P 260.2 mg (0.88 mmol) of the conjugated ketone compound 256 and 180 mg (1.05 mmol, 1.2 molar equivalents) of (R) - (+) -1- (1-naphthyl) ethylamine in chloroform / methanol was dissolved. (4: 1) and allowed to stand at room temperature for 13 days. After the reaction was completed, the solvent was distilled off under reduced pressure and the oil thus obtained was purified by column chromatography [gel W of silica, chloroform / methanol] to thereby give a colorless oil K-2312 (177.4 mg, 43.3%). 20 MS m / z: 468. NMR with H d: 1.61 (3H, d, J = 6.8 Hz, CH3), 2.63-2.71 (1H, m, CH2), 2.81-2.88 (2H, m, CH2), 2.95 (1H, d, J = 5.4 Hz, CH2), 3.78 (3H, d, J = 5.4 Hz, 0CH3), 4.22 (2H, d, J = 18.3 Hz, CH2), 4.27 (2H, d, J = 30.5 Hz, CH2), 4.81-4.86 (1H, m, CH), 6. 72 (1H, d, J = 8.5 Hz, Ar-H), 6.74 (1H, d, J = 8.5 Hz, Ar-H), 25 6.82 (1H, d, J = 8.8 Hz, Ar-H), 6.83 (1H, d, J = 8.5 Hz, Ar-H), 6. 85 (1H, d, J = 8.5 Hz, Ar-H), 6.98 (1H, d, J = 8.8 Hz, Ar-H), 7.02 (1H, d, J = 8.5 Hz, Ar-H), 7.10 ( 1H, d, J = 8.5 Hz, Ar-H), 7.45-7.54 (3H, m, Ar-H), 7.77 (2H, d, J = 7.6 Hz, Ar-H), 7.88 (1H, d, J = 8.1 Hz, Ar-H), 8.11 (1H, d, J = 8.1 Hz, Ar-H).

PLE 122 SYNTHESIS OF K-2280 (N-f5- [(4-METOXYPENYL) UNCLE] PENTIL-N- [(IR) -1- (1-NAFTHYL) ETHYL] AMIN) 753 mg (5.37 mmoles) of 4-methoxyphenol was dissolved in 10 ml of acetonitrile. It was added successively to the solution thus obtained, at room temperature, 754 mg (5.46 mmoles) of potassium carbonate and 0.73 ml (5.35 mmoles) of 1,5-dibromopentane, and the reaction mixture was stirred at room temperature for 3 hours. After confirming that the reaction was complete by means of TLC, 931 mg (6.75 mmoles) of potassium carbonate and 0.52 ml (3.22 mmoles) of (R) - (+) were added to the reaction system at the same temperature. -1- (1-naphthyl) ethylamine. In addition, the reaction mixture was stirred at 85 ° C for 12 hours. After the reaction was completed, the mixture was cooled by allowing it to stand at room temperature and water was added. The reaction mixture was then subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give a pale yellow compound in the form of syrup K-2280, as a free compound. Subsequently, 5 ml of 10% hydrochloric acid / methanol was poured into the K-22880 obtained above, and it was allowed to stand for 3 minutes, and then it was concentrated. The crystals thus obtained were subjected to Kiriyama filtration and the precipitate was washed with diethyl ether. 210 mg (0.55 mmol, yield of 20.6%) of K-2280 hydrochloride were obtained in this manner, as white crystals. 10 NMR at 400 MHz 10.49 (1H, broad s), 9.98 (1H, broad s), 8.24 F (1H, d, J = 7.32 Hz), 7.98 (1H, d, J = 8.56 Hz), 7.94 (1H, dd, J = 8.04 Hz, J = 1.48 Hz), 7.90 (1H, d, J = 8.28 Hz), 7.52-7.68 (3H, m), 7.19-7.23 (2H, m), 6.73-6.77 (2H, m), 5.14-5.24 (1H, m), 3. 73 (3H, s), 2.67-2.75 (2H, m), 2.65 (2H, t, J = 7.20 Hz), 2.02 (3H, d, J = 6.84 Hz), 1.91-1.99 (2H, m), 1.38-1.46 (2H, m), 1.21- 1.35 (2H, m), m / z = 379. f EXAMPLE 123 SYNTHESIS OF K-2281 (N- [(IR) -1- (1-NAFT L) ETHYL] -N-f4- [(2, 4, 5- 20 TRICLOROFENIL) UNCLE] BUTIL ')' AMINE) 770 mg (3.61 mmol) of 2,4-trichlorothiophenol was dissolved in 10 ml of acetonitrile. The solution thus obtained was successively added, at room temperature, 560 mg (4.05 mmoles) of potassium carbonate and 0.43 ml (3.60 mmoles) of 1,4-dibromobutane, and the reaction mixture was stirred at room temperature for 3 hours. After confirming that the reaction was complete by means of TLC, 545 mg (3.94 mmol) of potassium carbonate and 0.41 ml (3.94 mmol) of (R) - (+) were added at the same temperature to the reaction system. -1- (1-naphthyl) ethylamine. In addition, the reaction mixture was stirred at 85 ° C for 12 hours. After the reaction was completed, the mixture was cooled by allowing it to stand at room temperature and water was added. The reaction mixture was then subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give a pale yellow compound in the form of syrup K-2281, as a free compound. Subsequently, 10 ml of 10% hydrochloric acid / methanol was poured into the K-2281 obtained above, and allowed to stand for 3 minutes, and then concentrated. The crystals thus obtained were subjected to Kiriyama filtration and the precipitate was washed with diethyl ether. 280 mg (0.59 mmol, yield of 15.06%) of K-2281 hydrochloride were obtained in this manner, as white crystals. NMR at 400 MHz 10.64 (1H, broad s), 10.07 (1H, broad s), 8.26 (1H, dd, J = 7.3 Hz, J = 0.7 Hz), 8.01 (1H, d, J = 8.3 Hz), 7.90 -7.95 (2H, m), 7.52-7.68 (3H, m), 7.36 (1H, s), 7.11 (1H, s), 5.20-5.26 (1H, m), 2.76 (2H, t, J = 7.0 Hz ), 2.76-2.82 (2H, m), 2.87 (3H, d, J = 6.8 Hz), 1.53-1.63 (2H, m), m / z = 437, 439.

EXAMPLE 124 SYNTHESIS OF K-2282 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N-f5- [(2, 4, 5- TRICHLOROPHENYL) UNCLE] BUTILYAMINE) Dissolve in 15 ml of acetonitrile 1.53 g (7.15 mmol) of 2,4-trichlorothiophenol. The solution thus obtained was successively added, at room temperature, 1083 g (7.84 mmol) of potassium carbonate and 0.98 ml (7.19 mmol) of 1,5-dibromopentane, and the reaction mixture was stirred at room temperature. 2.5 hours. After confirming that the reaction was complete by means of TLC, 1.0 g (7.25 mmole) of potassium carbonate and 0.69 ml (4.27 mmole) of (R) - (+) were added to the reaction system at the same temperature. -1- (1-naphthyl) ethylamine. In addition, the reaction mixture was stirred at 85 ° C for 12 hours. After the reaction was completed, the mixture was cooled by allowing it to stand at room temperature and water was added. The reaction mixture was then subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give a pale yellow compound in the form of syrup K-2282, as a free compound. Subsequently, 15 ml of 10% hydrochloric acid / methanol was poured into K-2282 obtained above, and allowed to stand for 5 minutes, and then concentrated. The crystals thus obtained were subjected to Kiriyama filtration and the precipitate was washed with diethyl ether. Thereby obtained 283 mg (0.58 mmol, yield of 13.5%) of K-2282 hydrochloride, as white crystals. NMR at 400 MHz 10.55 (1H, broad s), 10.03 (1H, broad s), 8.25 (1H, d, J = 7.3 Hz), 8.00 (1H, d, J = 8.5 Hz), 7.90-7.95 (2H, m), 7.54-7.68 (3H, m), 7.37 (1H, s), 7.16 ( 1H, s), 5.17-5.26 (1H, m), 2.73-2.82 (4H, m), 1.97-2.05 (2H, m), 2.05 (3H, d, J = 6.6 Hz), 1.52-1.60 (2H, m), 1.31-1.45 (2H, m), m / z = 451, 453.

EXAMPLE 125 SYNTHESIS OF K-2287 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (4-f [4- (TRIFLUOROMETOXY) PHENYL) UNCLE] BUTIL) AMIN) 908 mg (4.68 mmol) of 4-trifluoromethoxythiophenol was dissolved in 10 ml of acetonitrile. 679 mg was added successively to the solution thus obtained, at room temperature. (4.91 mmoles) of potassium carbonate and 0.568 ml (4.69 mmoles) of 1,4-dibromobutane, and the reaction mixture was stirred at room temperature for 5 hours. After confirming that the reaction had been completed by means of TLC, the reaction system was added at the same temperature, 710 mg (5.14 mmol) of potassium carbonate and 0.53 ml (3.28 mmol) of (R) - (+) -1- (1-naphthyl) ethylamine. In addition, the reaction mixture was stirred at 90 ° C for 12 hours. After the reaction was completed, the mixture was cooled by allowing it to stand at room temperature and water was added. The reaction mixture was then subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give a pale yellow compound in the form of syrup K-2287, as a free compound. Subsequently 10 ml of 10% hydrochloric acid / methanol was poured into K-2287 obtained above, and allowed to stand for 5 minutes, and then concentrated. The crystals thus obtained were subjected to Kiriyama filtration and the precipitate was washed with diethyl ether. 245 mg (0.54 mmol, 16.5% yield) of K-2287 hydrochloride were obtained in this manner, as white crystals. NMR at 400 MHz 10.58 (1H, broad s), 10.07 (1H, broad s), 8.25 (1H, d, J = 6.8 Hz), 8.00 (1H, d, J = 8.5 Hz), 7.90-7.96 (2H, m), 7.52-7.67 (3H, m), 7.15-7.19 (3H, m), 7.02-7.04 (2H, m), 5.19-5.24 (1H, m), 2.73-2.76 (4H, m), 2.06- 2.17 (2H, m), 2.06 (3H, d, J = 6.8 Hz), 1.41-1.59 (2H, m), m / z = 419.

EXAMPLE 126 SYNTHESIS OF K-2288 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (5-f [4- (TRIFLUOROMETOXY) PHENYL) UNCLE] PENTIL) MINE) Acetonitrile 995 mg (5.12 mmoles) of 4-trifluoromethoxythiophenol was dissolved in 10 ml of acetonitrile. Successively added to the obtained solution, at room temperature, 715 mg (5.17 mmol) of potassium carbonate and 0.70 ml (5.14 mmol) of 1,5-dibromopentane, and the reaction mixture was stirred at room temperature for 5 hours. hours. After confirming that the reaction was complete by means of TLC, 770 mg (5.57 mmol) of potassium carbonate and 0.58 ml (3.59 mmol) of (R) - were added to the reaction system at the same temperature. +) -1- (1-naphthyl) ethylamine. In addition, the reaction mixture was stirred at 85 ° C for 12 hours. After completing the reaction, the mixture was cooled by allowing it to stand at room temperature and water was added. The reaction mixture was then subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride, and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give a pale yellow compound, such as syrup, K-2288, as a free compound. Subsequently, 10 ml of 10% hydrochloric acid / methanol was poured into the K-2288 obtained above, and allowed to stand for 5 minutes, after which it was concentrated. The pale yellow crystals thus obtained were subjected to Kiriyama filtration and the precipitate was washed with hexane. Thus, 313 mg (0.67 mmol, yield 18.7%) of K-2288 hydrochloride were obtained as white crystals. NMR at 400 MHz 10.53 (1H, m), 10.03 (1H, broad s), 8.24-8.26 (1H, m), 7.99 (1H, d, J = 8.3 Hz), 7.52-7.67 (3H, m), 7.19-7.23 (2H, m), 7.04-7.07 (2H, m), 5.15-5.25 (1H, m), 2.76 (2H, t, J = 7.2 Hz), 2.69-2.78 (2H, m), 2.03 (3H, d , J = 6.8 Hz), 1.92-2.04 (2H, m), 1.49 (2H, tt, J = 7.4 Hz, J = 7.4 Hz), 1.27-1.38 (2H, m), m / z = 433.

EXAMPLE 127 SYNTHESIS OF K-2293 (N-f4- [(4- (CHLOROPHENYL) UNCLE] BUTIL -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMINE) 782 mg (5.41 mmoles) of 4-chlorothiophenol was dissolved in 10 ml of acetonitrile. Successively added to the obtained solution, at room temperature, 850 mg (6.15 mmol) of potassium carbonate and 0.65 ml (5.44 mmol) of 1,4-dibromobutane, and the reaction mixture was stirred at room temperature for 5 hours. hours . After confirming that the reaction was complete by means of TLC, 775 mg (5.61 mmol) of potassium carbonate and 0.62 ml (3.84 mmol) of (R) - (+) were added to the reaction system at the same temperature. ) -1- (1-naphthyl) ethylamine. In addition, the reaction mixture was stirred at 85 ° C for 24 hours. After completing the reaction, the mixture was cooled by allowing it to stand at room temperature and water was added. The reaction mixture was then subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride, and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give a pale yellow compound, such as syrup, K-2293, as a free compound. Subsequently, 10 ml of 10% hydrochloric acid / methanol was poured into the K-2293 obtained above, and allowed to stand for 5 minutes, after which it was concentrated. The pale yellow crystals thus obtained were subjected to filtration, and the precipitate was washed with hexane. 420 mg (1.03 mmol, yield 26.9%) of K-2293 hydrochloride were obtained in this manner, as white crystals. NMR at 400 MHz 10.58 (1H, broad s), 10.05 (1H, broad s), 8.25 (1H, d, J = 6.8 Hz), 7.99 (1H, d, J = 8.3 Hz), 7.94 (1H, dd, J = 8.0 Hz, J = 1.2 Hz), 7.91 (1H, d, J = 8.04 Hz), 7.52-7.67 (3H, m), 7. 12-7.16 (2H, m), 7.06-7.10 (2H, m), 5.16-5.25 (1H, m), 2.70- 2.74 (4H, m), 2.06-2.15 (2H, m), 2.05 (3H, d) , J = 6.6 Hz), 1.40-1.57 (2H, m), m / z = 369.

EXAMPLE 128 SYNTHESIS OF K-2240 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (3-f [4- (TRIFLUOROMETHYL) PHENYL) TI?) PROPYL) AMINE) K-2240 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol and 1,4-dibromobutane, respectively, by 4-trifluoromethyl-thiophenol and 1, 3 -dibromopropane, m / z = 389.

EXAMPLE 129 SYNTHESIS OF K-2263 (N-f4- [(4- (FLUOROFENYL) UNCLE] BUTIL -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMIN) The K-2263 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol with 4-fluorothiophenol. NMR at 400 MHz 10.57 (1H, broad s), 10.04 (1H, broad s), 8.24 (1H, d, J = 7.3 Hz), 7.99 (1H, d, J = 8.52 Hz), 7.90-7.96 (2H, m), 7.52-7.67 (3H, m), 7.15-7.20 (2H, m), 6.86-6.92 (2H, m), 5.19-5.22 (1H, m), 2.67-2.77 (2H, m), 2.69 ( 2H, t, J = 7.1 Hz), 2.05-2.15 (2H, m), 2.05 (3H, d, J = 6.8 Hz), 1.36-1.54 (2H, m), m / z = 353.

EXAMPLE 130 SYNTHESIS OF K-2269 (N-f4- [(3- (METOXYPENYL) UNCLE] BUTIL) -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMIN) The K-2269 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol with 3-methoxyphenol. NMR at 400 MHz 10.58 (1H, broad s), 10.06 (1H, broad s), 8.24-8.26 (1H, m), 7.99 (1H, d, J = 8.3 Hz), 7.88-7.94 (3H, m), 7.53-7.67 (3H, m), 7.08 (1H, dd, J = 8.3 Hz), 6.71-6.74 (2H, m), 6.64 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = l. 0 Hz), 5.15-5.25 (1H, m), 2.70-2.79 (2H, m), 2.75 (2H, t, J = 7.2 Hz), 2.07-2.16 (2H, m), 2.05 (3H, d, J = 6.8 Hz), 1.43-1.60 (2H, m), m / z = 365.

EXAMPLE 131 SYNTHESIS OF K-2271 (N-f [4- (5-ETOXY-1, 3-BENZOTIAZOL-2-IL) THYO] BUTIL) -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMIN) The K-2271 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol with 6-ethoxy-2-mercaptobenzothiazole. NMR at 400 MHz 10.56 (1H, broad s), 10.04 (1H, broad s), 8.29 (1H, d, J = 7.0 Hz), 8.02 (1H, d, J = 8.5 Hz), 7.87-7.92 (2H, m), 7.52-7.70 (4H, m), 7.13 (1H, d, J = 2.2 Hz), 6.96 (1H, dd, J = 8.8 Hz, J = 2.2 Hz), 5.20-5.28 (1H, m), 4.02 (2H, dd, J = 13.9 Hz, J = 7.1 Hz), 3.27 (2H, dd, J = 7.1 Hz, J = 7.1 Hz), 2.20-2.60 (4H, m), 2.12-2.23 (2H, m ), 2.06 (3H, d, J = 6.6 Hz), 1.76-1.87 (2H, m), 1.42 (3H, t, J = 6.8 Hz), m / z = 436. 5 EXAMPLE 132 SYNTHESIS OF K-2279 ( Nf [5- (3-METOXYPENYL) UNCLE] PENTIL> -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMIN) Hydrochloride K-2279 was obtained as crystals ?? blanks, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol and 1,4-dibromobutane, respectively by 3-methoxythiophenol and 1,5-dibromopentane. 15 NMR at 400 MHz 10.51 (1H, broad s), 9.99 (1H, broad s), 8.24 (1H, d, J = 7.1 Hz), 7.89-7.99 (3H, m), 7.54-7.67 (3H, m), 7.10 (1H, dd, J = 7.9 Hz, J = 7.9 Hz), 6.75-6.79 (2H, m), 6.61-6.65 (1H, f ddd, J = 8.0 Hz, J = 2.4 Hz, J = 0.7 Hz), 5.14-5.24 (1H, m), 3.72 (3H, s), 2.68-2.79 (4H, m), 2.03 (3H, d, J = 6.8 Hz), 1.93-1.99 (2H, m), 1.47-1.54 (2H, m), 1.24-1.38 (2H, m), m / z = 379.

EXAMPLE 133 SYNTHESIS OF K-2284 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (5-f [2, 3, 5, 6 - TETRAFLU0R0-4- (TRIFLUOROMETHYLENE) PHENYL] TI ?) PENTIL) MINE) 25 The K-2284 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol and the 1,4-dibromobutane, respectively, 2, 3, 5, 6-tetrafluoro-4-trifluoromethylthiophenol and 1,5-dibromopentane. NMR at 400 MHz 10.54 (1H, broad s), 10.43 (1H, broad s), 8.24 (1H, d, J = 6.6 Hz), 7.99 (1H, d, J = 8.3 Hz), 7.90-7.96 (2H, m), 7. 55-7.67 (3H, m), 5.15-5.25 (1H, broad s), 2.91 (2H, t, J = 7.2 Hz), 2.70-2.80 (2H, m), 2.04 (3H, d, J = 6.6 Hz), 1.93-2.02 (2H | m), 1.48 (2H, tt, J = 7.4 Hz, J = 7.4 Hz), 1.26-1.41 (2H, m), m / z = 489.

EXAMPLE 134 SYNTHESIS OF K-2286 (N- { 6- [(4-CHLOROPHENYL) UNCLE] HEXIL > -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMINE) The K-2286 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 1,4-dibromobutane with and 1,6-dibromohexane. m / z = 397.

EXAMPLE 135 SYNTHESIS OF K-2292 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (7- { [2, 3, 5, 6-TETRAFLUORO-4- (TRIFLUOROMETHYLENE) PHENYL ] TI?) HEPTIL) AMINA) The K-2292 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol and 1,4-dibromobutane, respectively by 2, 3, 5, 6 -tetrafluoro-4-trifluoromethylthiophenol and 1,5-dibromopentane. NMR at 400 MHz 10.48 (1H, broad s), 9.98 (1H, broad s), 8.26 (1H, d, J = 6.8 Hz), 8.00 (1H, d, J = 8.3 Hz), 7.94 (1H, d, J = 7.3 Hz), 7.91 (1H, d, J = 8.0 Hz), 7.54-7.68 (3H, m), 5.21 (1H, broad s), 2.92 (2H, t, J = 7.3 Hz), 2.74 (2H, broad s), 2.05 (3H, d, J = 5.1 Hz), 1.97 (2H, s broad), 1.42-1.50 (2H, m), 1.23-1.38 (2H, m), 1.17 (4H, broad s), m / z = 517.

EXAMPLE 136 SYNTHESIS OF K-2295 The K-2295 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol and the 1,4-dibromobutane, respectively by 2, 4, 5-trichlorothiophenol and l-bromo-2-chloroethane. NMR at 400 MHz 10.94 (1H, broad s), 10.31 (1H, broad s), 8.17 (1H, d, J = 6.6 Hz), 7.88-7.96 (3H, m), 7.55-7.65 (3H, m), 7.42 (1H, s), 7.29 (1H, s), 5.20-5.28 (1H, m), 3.47-3.59 (2H, m), 2.92-3.07 (2H, m), 2.03 (3H, d, J = 6.6 Hz), m / z = 409.

EXAMPLE 137 SYNTHESIS OF K-2296 (N-f [5- (2, 5-DICHLOROPHENYL) UNCLE] PENTIL -N- [(1R) -1- (1-NAFTHYL) ETHYL] AMIN) The K-2296 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol and 1,4-dibromobutane, respectively, by 2,5-dichlorothiophenol and 1, 5-dibromopent no. NMR at 400 MHz 10.63 (1H, broad s), 10.08 (1H, broad s), 8.26 (1H, d, J = 6.8 Hz), 8.01 (1H, d, J = 8.5 Hz), 7.90-7.94 (2H, m), 7.52-7.68 (3H, m), 7.18 (1H, d, J = 8.3 Hz), 6.98-7.02 (2H, m), 5.18-5.28 (1H, m), 2.75-2.84 (2H, m) , 2.77 (2H, t, J = 7.2 Hz), 2.12-2.20 (2H, m), 2.07 (3H, d, J = 6.6 Hz), 1.56-1.67 (4H, m), m / z = 417.

EXAMPLE 138 SYNTHESIS OF K-2297 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (4-f [2, 3, 5, 6-TETRAFLUORO-4- (TRIFLUOROMETHYL) PHENYL] TIOlBUTIL AMINA) The K-2297 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol by 2,3,5,6-tetrafluoro-4-trifluoromethylthiophenol. NMR at 400 MHz 10.59 (1H, wide), 10.08 (1H, broad s), 8.23 (1H, d, J = 6.6 Hz), 8.00 (1H, d, J = 8.3 Hz), 7.94 (1H, sd , J = 8.0 Hz, J = 1.2 Hz), 7.55-7.67 (3H, m), 5.18-5.23 (1H, m), 2.89 (2H, t, J = 7.3 Hz), 2.70-2.82 (2H, m) , 2.04-2.13 (2H, m), 2.05 (3H, d, J = 6.6 Hz), 1.47-1.60 (2H, m), m / z = 475.

EXAMPLE 139 SYNTHESIS OF K-2298 (N-f4- [(2,5-DICHLOROPHENYL) UNCLE] BUTIL.}. -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMINE) The K-2298 hydrochloride was obtained as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol with 2,5-dichlorothiophenol. NMR at 400 MHz 10.64 (1H, broad s), 10.09 (1H, broad s), 8.26 (1H, d, J = 6.6 Hz), 8.01 (1H, d, J = 8.3 Hz), 7.89-7.94 (2H, m), 15 7.52-7.68 (3H, m), 7.18 (1H, d, J = 8.3 Hz), 7.01 (1H, dd, J = 6.6 Hz, J = 2.4 Hz), 5.18-5.28 (1H, m) , 2.73-2.85 (2H, m), 2.76 (2H, t, J = 7.2 Hz), 2.16 (2H, tt, J = 7.2 Hz, J = 7.2 Hz), 2.07 (3H, d, J = 6.8 Hz) , 1.52-1.68 (2H, m), m / z = 403.

EXAMPLE 140 SYNTHESIS OF K-2301 (N- [(IR) -1- (1-NAFTHYL) ETHYL] -N- (6-f [4- (TRIFLUOROMETOXY) PHENYL] TIOTHEXYL) MINE) The K-2301 hydrochloride was obtained, as crystals targets, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol and 1,4-dibromobutane, respectively, by 4-trifluoromethoxythiophenol and 1,6-dibromohexane. NMR at 400 MHz 10.53 (1H, broad s), 10.00 (1H, broad s), 8.27 (1H, d, J = 7.3 Hz), 8.00 (1H, d, J = 8.3 Hz), 7.89-7.95 (2H, m), 7.52-7.68 (3H, m), 7.21-7.24 (2H, m), 7.05-7.08 (2H, m), 5.21 (1H, broad s), 2.70-2.78 (2H, m), 2.76 (2H , t, J = 7.3 Hz), 2.06 (3H, d, J = 6.6 Hz), 1.92-2.02 (2H, m), 1.46-1.54 (2H, m), 1.17- 1.35 (4H, m), m / z = 447.

EXAMPLE 141 SYNTHESIS OF K-2302 (N-f4- [(2,4-DIMETHYLPHENYL) UNCLE] BUTIL) -N- [(IR) -1- (1-NAFTHYL) ETHYL] AMYL) The K-2302 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol by 2,4-dimethylthiophenol. NMR at 400 MHz 10.60 (1H, broad s), 10.05 (1H, broad s), 8.25 (1H, d, J = 7.3 Hz), 7.99 (1H, d, J = 8.6 Hz), 7.93 (1H, d, J = 7.84 Hz), 7.89 (1H, d, J = 8.3 Hz), 7.51-7.66 (3H, m), 7.00 (1H, d, J = 7.8 Hz), 6.90 (1H, s), 6.83 (1H, d, J = 7.8 Hz), 5.15-5.24 (1H, m), 2.70-2.78 (2H, m), 2.66 (2H, t, J = 7.2 Hz), 2.22 (6H, s), 2. 07-2.13 (2H, m), 2.05 (3H, d, J = 6.8 Hz), 1.40-1.55 (2H, m), m / z = 363. 25 EXAMPLE 142 SYNTHESIS OF K-2303 (N-f5- [ (2, 4-DIMET LFENIL) UNCLE] PENTIL > -N- [(1R) -1- (1-NAFTHYL) ETHYL] AMIN) K-2303 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol and the 1,4-dibromobutane, respectively, 2,4-dimethylthiophenol and 1, 5-dibromohexane. 10 NMR at 400 MHz 10.51 (1H, broad s), 10.00 (1H, broad s), 8.25 (1H, d, J = 7.1 Hz), 7.98 (1H, d, J = 8.3 Hz), 7.94 (1H, dd, J = 7.8 Hz, J = 1.2 Hz), 7.90 (1H, d, J = 8.3 Hz), 7.53-7.67 (3H, m), 7.05 (1H, d, J = 7.8 Hz), 6.90 (1H, s), 6.85 (1H, d, J = 7.8 Hz), 5.14- 5.23 (1H, m), 2.67-2.78 (2H, m), 2.67 ( 2H, t, J = 7.3 Hz), 2.24 (3H, s), 2.21 (3H, s), 2.02 (3H, d, J = 6.6 Hz), 1.92-2.01 (2H, m), 1.43-1.51 (2H, m), 1.27-1.34 (2H, m), m / z = 377.

EXAMPLE 143 SYNTHESIS OF K-2304 (N-f4- [(4-METHYLPHENYL) THYO] BUTIL > -N- [(IR) -1-20 (1-NAFTHYL) ETHYL] AMIN) The K-2304 hydrochloride was obtained, as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol with 4-25 methylthiophenol. NMR at 400 MHz 10.55 (1H, broad s), 10.03 (1H, broad s), 8.25 (1H, d, J = 7.1 Hz), 7.99 (1H, d, J = 8.5 Hz), 7.93-7.95 (1H, m), 7.89 (1H, d, J = 8.0 Hz), 7.06-7.86 (5H, m), 6.96-6.99 (2H, m), 5.18-5.22 (1H, m), 2.68-2.77 (2H, m) , 2.69 (2H, t, J = 7.2 Hz), 2.25 (3H, s), 2.04-2.14 (2H, m), 2.04 (3H, d, J = 6.6 Hz), 1.37-1.55 (2H, m), m / z = 349.

EXAMPLE 144 SYNTHESIS OF K-2305 (N-f5- [(4-METHYLPHENYL) UNCLE] PENTILl-N- [(IR) -1- (1-NAFTHYL) ETHYL] AMIN) The K-2305 hydrochloride was obtained as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol and the 1,4-dibromobutane, respectively, by 4-methylthiophenol and 1,5-dibromopentane. NMR at 400 MHz 10.50 (1H, broad s), 9.99 (1H, broad s), 8.25 (1H, d, J = 7.1 Hz), 7.98 (1H, d, J = 8.3 Hz), 7.94 (1H, dd, J = 7.8 Hz, J = 1.2 Hz), 7.89 (1H, d, J = 8.3 Hz ), 7.52-7.66 (3H, m), 7.11- 7.13 (2H, m), 6.98-7.00 (2H, m), 5.18 (1H, broad), 2.68-2.73 (2H, m), 2.71 (2H, t, J = 7.2 Hz), 2.24 (3H, s), 2.02 (3H, d, J = 6.6 Hz), 1.91-1.99 (2H, m), 1.42-1.50 (2H, m), 1.26-1.34 (2H, m), m / z = 363.

EXAMPLE 145 SYNTHESIS OF 2275 The K-2275 hydrochloride was obtained as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol and the 1,4-dibromobutane, respectively, by 3-trifluoromethyl-thiophenol and l-bromo-2-chloroethane. NMR at 400 MHz 10.88 (1H, broad s), 10.25 (1H, broad s), 8.16 (1H, d, J = 6.6 Hz), 7.87-7.95 (3H, m), 7.52-7.65 (3H, m), 7.40 () 1H, broad s), 7.31-7.34 (2H, m), 7.21-7.26 (1H, m), 5.18-5.28 (1H, m), 3.53 (2H, t, J = 7.7 Hz), 2.91- 3.06 (2H, m), 2.01 (3H, d, J = 6.84 Hz), m / z = 375.

EXAMPLE 146 SYNTHESIS OF 2314 The K-2314 hydrochloride was obtained as white crystals, by the same method that was used for the synthesis of K-2293 but replacing the 4-chlorothiophenol with 4-methoxythiophenol. NMR at 400 MHz 10.55 (1H, broad s), 10.03 (1H, broad s), 8.25 (1H, d, J = 7.4 Hz), 7.99 (1H, d, J = 87.5 Hz), 7.89-7.95 (2H, m), 7. 52-7.68 (3H, m), 7.15-7.18 (2H, m), 6.71-6.75 (2H, m), 5.18-5.22 (1H, m), 3.74 (3H, s), 2.67-2.76 (2H, m ), 2.64 (2H, t, J = 7.1 Hz), 2.03-2.15 (2H, m), 2.05 (2H, d, J = 6.8 Hz), 1.32-1.50 (2H, m), m / z = 365.

EXAMPLE 147 SUMMARY OF 2008 The K-2008 hydrochloride was obtained as white crystals, by the same method that was used for the synthesis of K-2293 but replacing 4-chlorothiophenol, 1,4-dibromobutane and (R) - (+) -1- (1-naphthyl) ethylamine, respectively, by 3-trifluoromethylthiophenol, l-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-methylbenzylamine, m / z = 355.

EXAMPLE 148 S NTESIS OF S-l 580 mg (4.20 mmoles) of 2,5-dimethylphenol was dissolved in 6 ml of acetonitrile. Successively added to the obtained solution, at room temperature, 785 mg (5.68 mmol) of potassium carbonate and 0.35 ml (4.21 mmol) of 1-bromo-2-chloroethane, and the reaction mixture was stirred at room temperature for 2.5 hours. After confirming that the reaction was completed, by means of TLC, 730 mg (5.28 mmol) of potassium carbonate and 500 mg (3.30 mmol) of (R) - (+) were added at the same temperature to the reaction system. -3-methoxy-O-benzylmethylamine. In addition, the reaction mixture was stirred at 909 ° C for 24 hours. After the reaction was complete, the mixture was cooled allowing it to stand at room temperature and water was added. The reaction mixture was then subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The organic residue was purified by means of silica gel column chromatography (chloroform: methanol = 200: 1) to thereby give a pale yellow compound in the form of syrup S-1 (332 mg., 1.05 mmoles, yield 31.8%). NMR with H at 500 MHz, 7.30 (1H, d, J = 8.0 Hz), 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.06 (1H, s), 6.86-6.90 (3H, m), 6.75-6.78 (1H, m), 3.80 (3H, m), 3.74 (1H, c, J = 6.5 Hz), 2.95-3.03 (2H, m), 2.68-2.77 (2H, m), 2.32 (3H, s), 2.27 (3H, s), 1.34 (3H, d, J = 6.5 Hz), m / z = 315.

EXAMPLE 149 SYNTHESIS OF S-2 S-2 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing l-bromo-2-chloroethane by 1,3-dibromopropane. NMR with 1H at 500 MHz, 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.06 (1H, s), 7.02 (1H, d, J = 7.5 Hz), 6.86-6.88 (3H, m), 6.76-6.78 (1H, m), 3.80 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.85-2.96 (2H, m), 2.53-2.66 (2H, m), 2.29 (3H, s), 2.28 (3H, s), 1.74-1.82 (2H, m), 1.33 (3H, d, J = 6.5 Hz), m / z = 329.

EXAMPLE 150 SYNTHESIS OF S-3 S-3 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing l-bromo-2-chloroethane by 1,4-dibromobutane. NMR at 500 MHz, 7.22 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 7.04 (1H, s), 7.03 (1H, d, J = 8.0 Hz), 6.85-6.89 (3H, m) , 6.75-6.78 (1H, m), 3.80 (3H, s), 3.71 (1H, c, J = 6.8 Hz), 2.85 (2H, t, J = 7.3 Hz), 2.42-2.55 (2H, m), 2.30 (3H, s), 2.29 (3H, s), 1.56-1.70 (4H, m), 1.33 (3H, d, J = 6.8 Hz), m / z = 343.

EXAMPLE 151 SYNTHESIS OF S-4 S-4 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing l-bromo-2-chloroethane by 1,5-dibromopentane. NMR with 500 MHz XH, 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 7.05 (1H, s), 7.03 (1H, d, J = 7.5 Hz), 6.87-6.88 (3H, m ), 6.76-6.78 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.85 (2H, t, J = 7.5 Hz), 2.40-2.51 (2H, m) , 2.31 (3H, s), 2.30 (3H, s), 1.61-1.67 (4H, m), 1.42-1.51 (4H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 357 .

EXAMPLE 152 SYNTHESIS OF S-5 S-5 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing l-bromo-2-chloroethane by 1,6-dibromohexane. NMR with H at 500 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.05 (1H, s), 7.03 (1H, d, J = 8.0 Hz), 6.86-6.89 (3H, m ), 6.76-6.78 (3H, m), 3.81 (3H, s), 3.72 (1H, c, J = 7.0 Hz), 2.85 (2H, t, J = 7.3 Hz), 2.39-2.52 (2H, m) , 2.31 (3H, s), 2.30 (3H, s), 1.61-1.67 (2H, m), 1.39-1.50 (4H), 1.34 (3H, d, J = 7.0 Hz), 1.29-1.34 (2H, m ), m / z = 371.

EXAMPLE 153 SYNTHESIS OF S-6 S-6 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing l-bromo-2-chloroethane with 1,7-dibromoheptane. NMR with 500 MHz XH, 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.05 (1H, s), 7.03 (1H, d, J = 7.5 Hz), 6.80-6.86 (3H, m), 6.75-6.78 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.8 Hz), 2.85 (2H, t, J = 7.5 Hz), 2.38-2.51 (2H, m), 2.31 (3H, s), 2.29 (3H, s) 1.60- 1.66 (2H, m), 1.37-1.48 (4H, m), 1.34 (3H, d, J = 6.8 Hz), 1.27-1.30 (4H, m), m / z = 385.

EXAMPLE 154 SYNTHESIS OF S-7 S-7 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing l-bromo-2-chloroethane by 1,8-dibromooctane. NMR with 1H at 500 MHz, 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 7.06 (1H, s), 7.03 (1H, d, J = 8.0 Hz), 6.87-6.89 (3H, m ), 6.75-6.78 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.86 (2H, t, J = 7.5 Hz), 2.39-2.51 (2H, m) , 2.31 (3H, s), 2.30 (3H, s), 1.61-1.67 (2H, m), 1.38-1.47 (4H, m), 1.34 (3H, d, J = 6.5 Hz), 1.23-1.31 (6H , m), m / z = 399.

EXAMPLE 155 SYNTHESIS OF S-8 S-8 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the (R) - (+) - 3-methoxy-O-benzylmethylamine by (R) - (+) -1- (1 -naphthyl) ethylamine. NMR with H at 500 MHz, 8.16 (1H, d, J = 8.8 Hz), 7.83-7.87 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 7.1 Hz ), 7.42-7.51 (3H, m), 7.05 (1H, s), 7.03 (1H, d, J = 8.0 Hz), 6.88 (1H, d, J = 7.8 Hz), 4.63 (1H, c, J = 6.6 Hz), 3.05 (2H, t, J = 6.6 Hz), 2. 77-2.87 (2H, m), 2.32 (3H, s), 2.24 (3H, s), 1.49 (3H, d, J = 6.6 Hz), m / z = 335.

EXAMPLE 156 SYNTHESIS OF S-9 S-9 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 1-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 1,3-dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 500 MHz, 8.18 (1H, d, J = 8.3 Hz), 7.83-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 6.8 Hz ), 7.44-7.52 (3H, m), 7.25 (1H, s), 7.06 (1H, s), 7.02 (1H, d, J = 7.7 Hz), 6. 87 (1H, d, J = 7.7 Hz), 4.62 (1H, c, J = 6.6 Hz), 2.87-3.00 (2H, m), 2.64-2.77 (2H, m), 2.28 (3H, s), 2.27 (3H, s), 1.81-1.88 (2H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 349.

EXAMPLE 157 SYNTHESIS OF S-10 S-10 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 1-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with ^ -H at 500 MHz, 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.66 (1H, d, J = 6.8 Hz), 7.03 (1H, s), 7.01 (1H, d, J = 7.8 Hz), 6.86-6.89 (1H, m), 4.64 (1H, c, J = 6.2 Hz), 2.85 (2H, t, J = 6.8 Hz), 2.55-2.65 (2H, m), 2.30 (3H, s), 2.28 (3H, s), 1.65-1.70 (4H, m), 1.50 (3H, d, J = 6.2 Hz), m / z = 363.

EXAMPLE 158 SYNTHESIS OF S-ll S-11 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 1-10 bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively , by 1, 5-dibromopentane (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 500 MHz, 8.45 (1H, d, J = 8.0 Hz), 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (2H, d, J = 8.3 Hz ), 7.64 (1H, d, J = 7.1 Hz), 7.42-7.52 (3H, m), 7.01-7.04 (2H, m), 6.87 (1H, c, J = 7.6 Hz), 4.62 (1H, c, J = 6.5 Hz) , 2.85 (2H, t, J = 7.3 Hz), 2.51-2.63 (2H, m), 3.00 (3H, s), 2.29 (3H, s), 1.61-1.68 (2H, m), 1.44-1.57 (4H , m), 1.49 (3H, d, J = 6.5 Hz), m / z = 377.

EXAMPLE 159 SYNTHESIS OF S-12 S-12 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 1-25 bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 1, 6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 500 MHz, 8.17 (1H, d, J = 8.3 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 7.1 Hz), 7.40-7.52 (3H, m), 6.06-6.98 (2H, m), 6.87 (1H, d, J = 7.6 Hz), 4.62 (1H, c, J = 6.6 Hz), 2.84 (2H, t, J = 7.3 Hz), 2.49-2.63 (2H, m) , 2.30 (3H, s), 2.29 (3H, s), 1.59-1.67 (2H, m), 1.46-1.55 (2H, m), 1.49 (3H, d, J = 6.6 Hz), 1.27-1.46 (4H , m), m / z = 391.

EXAMPLE 160 S NTESIS OF S-13 S-13 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 1-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 1, 7-dibromoheptane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 500 MHz, 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.68 (1H, d, J = 7.1 Hz ), 7.41-7.53 (3H, m), 7.04 (1H, s), 7.02 (1H, d, J = 7.6 Hz), 6.87 (1H, d, J = 7.6 Hz), 4.66 (1H, c, J = 6.5 Hz), 2.84 (2H, t, J = 7.3 Hz), 2.30 (3H, s), 2.29 (3H, s), 1.58-1.66 (2H, m), 1.53 (3H, d, J = 6.5 Hz), 1.34-1.44 ( 2H, m), 1.26-1.30 (4H, m), m / z = 405.

EXAMPLE 161 SYNTHESIS OF S-14 S-14 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 1-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 1,8-dibromooctane and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 419.

EXAMPLE 162 SYNTHESIS OF S-15 S-15 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 1-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 1, 10-dibromodecane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.18 (1H, d, J = 8.6 Hz), 7.83-7.88 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.65 (1H, d, J = 6.8 Hz ), 7.40-7.52 (3H, m), 7.06 (1H, s), 7.03 (1H, d, J = 7.6 Hz), 6.87 (1H, d, J = 7.6 Hz), 4.63 (1H, c, J = 6.5 Hz), 2.86 (2H, t, J = 7.3 Hz), 2. 50-2.62 (2H, m), 2.31 (3H, s), 2.30 (3H, s), 1.60-1.70 (2H, m), 1.49 (3H, d, J = 6.5 Hz), 1.20-1.50 (14H, m), m / z = 447.

EXAMPLE 163 SYNTHESIS OF S-16 S-16 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 1-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 1,22-dibromododecane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.65 (1H, d, J = 7.1 Hz), 7.46-7.53 (3H, m), 7.06 (1H, s), 7.03 (1H, d, J = 7.8 Hz), 6.87 (1H, d, J = 7.8 Hz), 4.63 (1H, c, J = 6.6 Hz), 2.87 (2H, t, J = 7.4 Hz), 2.50-2.63 (2H, m), 2.31 (3H, s), 2.30 (3H, s), 1.61-1.69 (2H, m), 1.15 -1.55 (18H, m), 1.50 (3H, d, J = 6.6 Hz), m / z = 475.

EXAMPLE 164 SYNTHESIS OF S-17 S-17 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 2,4-dimethylthiophenol. NMR with XH at 400 MHz, 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.14 (1H, d, J = 8.0 Hz), 6.98 (1H, s), 6.90-6.92 (1H, m), 6.85-6.88 (2H, m), 6.75-6.81 (1H, m), 3.80 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.93-2.97 (2H, m), 2.62-2.74 (2H, m ), 2.34 (3H, s), 2.27 (3H, s), 1.33 (3H, d, J = 6.6 Hz), m / z = 315.

EXAMPLE 165 SYNTHESIS OF S-18 S-18 was synthesized by almost the same method as 5 was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,4-dimethylthiophenol and 1, 3 -dibromopropane. NMR with 1H at 400 MHz, 7.22 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 7.16 (1H, d, J = 7.8 Hz), 6.98 (1H, s), 6.92-6.95 (1H, m ), 6.86-6.88 10 (2H, m), 6.75-6.79 (1H, m), 3.80 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.80-2.93 (2H, m), 2.51 -2.65 (2H, m), 2.32 (3H, s), 2.28 (3H, s), 1.70-1.81 (2H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 329.

EXAMPLE 166 15 SYNTHESIS OF S-19 It was synthesized S-19 by almost the same method as á? It was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2, 4-dimethylthiophenol and 1,4-dibromobutane. NMR with 1H at 400 MHz, 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 7.16 (1H, d, J = 7.8 Hz), 6.98 (1H, similar as), 6.93-6.95 (1H, m), 6.86-6.88 (2H, m), 6.75-6.79 (1H, m), 3.80 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.81 (2H, t, J = 6.9 Hz ), 2.40-2.54 (2H, m), 2.33 (3H, s), 2.28 (3H, s), 1.50-1.66 (4H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 343.

EXAMPLE 167 SYNTHESIS OF S-20 S-20 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,4-dimethylthiophenol and 1, 5 dibromopentane. NMR with 1H at 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.16 (1H, d, J = 7.8 Hz), 6.98 (1H, s), 6.95 (1H, d, J = 8.0 Hz), 6.66-6.89 (2H, m), 6.70-6.79 (1H, m), 3.81 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.81 (2H, t, J = 7.3 Hz), 2.38-2.52 (2H, m), 2.33 (3H, s), 2.28 (3H, s), 1.56-1.64 (2H, m), 1.35-1.50 (4H, m), 1.34 (3H, d , J = 6.6 Hz), m / z = 357.

EXAMPLE 168 SYNTHESIS OF S-21 S-21 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,4-dimethylthiophenol and 1, 6 dibromohexane NMR with 1H at 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.16 (1H, d, J = 7.8 Hz), 6.98 (1H, s), 6.93-6.96 (1H, m ), 6.87-6.90 (2H, m), 6.75-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.81 (2H, t, J = 7.3 Hz) , 2.38-2.51 (2H, m), 2.34 (3H, s), 2.28 (3H, s), 1.56-1.64 (2H, m), 1.24-1.50 (6H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 371.

EXAMPLE 169 SYNTHESIS OF S-22 5 S-22 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2,4-dimethylthiophenol and 1,7-dibromoheptane. 10 NMR with 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.16 (1H, d, J = 7.8 Hz), 6.99 (1H, s), 6.93-6.96 (1H, m), 6.87-6.90 (2H, m), 6.73-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.81 (2H, t, J = 7.4 Hz), 2.37-2.51 (2H, m), 2.34 (3H, s), 2. 28 (3H, s), 1.56-1.64 (2H, m), 1.24-1.46 (8H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 385.

EXAMPLE 170 SYNTHESIS OF S-23 • S-23 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,4-dimethylthiophenol and 1,8. -dibromooctane. NMR with XH at 400 MHz, 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 7.17 (1H, d, J = 8.0 Hz), 6.99 (1H, s), 6.95 (1H, d, J = 8.0 Hz), 6.87-6.89 (1H, m), 6.75-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.82 (2H, t, J = 7.5 Hz), 2.38-2.52 (2H, m), 2.34 (3H, s), 2.28 (3H, s), 1.55-1.64 (2H, m), 1.20-1.50 (10H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 399.

EXAMPLE 171 SYNTHESIS OF S-24 S-24 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2, 4-dimethylthiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.15 (1H, d, J = 8.16 Hz), 7.83-7.90 (1H, m), 7.72 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 7.3 Hz ), 7.42-7.52 (3H, m), 7.14 (1H, d, J = 7.8 Hz), 6.98 (1H, s), 6.87-6.90 (1H, m), 4.61 (1H, c, J = 6.5 Hz) , 3.02 (2H, t, J = 8.7 Hz), 2.73-2.81 (2H, m), 2.34 (3H, s), 2.27 (3H, s), 1.48 (3H, d, J = 6.5 Hz), m / z = 335.

EXAMPLE 172 SYNTHESIS OF S-25 S-25 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,4-dimethylthiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 349.

EXAMPLE 173 SYNTHESIS OF S-26 S-26 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,4-dimethylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.15 (1H, d, J = 8.31 Hz), 7.85-7.87 (1H, m), 7.23 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 7.1 Hz ), 7.15 (1H, d, J = 7.8 Hz), 6.98 (1H, s), 6.93-6.95 (1H, m), 4.62 (1H, c, J = 6.6 Hz), 2.80 (2H, t, J = 7.3 Hz), 2.48-2.62 (2H, m), 2.35 (3H, s), 2.27 (3H, s), 1.57-1.63 (2H, m), 1.43-1.53 (2H, m), 1.25-1.44 (4H , m), 1.49 (3H, d, J = 6.6 Hz), m / z = 391.

EXAMPLE 174 SYNTHESIS OF S-27 S-27 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,4-dimethylthiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.15 (1H, d, J = 8.3 Hz), 7.87 (1H, d, J = 6.0 Hz), 7.68-7.78 (2H, m), 7.45-7.55 (3H, m), 7.15 (1H, d, J = 7.8 Hz), 6.98 (1H, s), 6.94 (1H, d, J = 7.8 Hz), 4.69 (1H, C, J = 6.6 Hz), 2.79 (2H, t, J = 7.3 Hz), 2.50-2.63 (2H, m), 2.33 (3H, s), 2.27 (3H, s), 1.14-1.62 (13H, m), m / z = 405.

EXAMPLE 175 SYNTHESIS OF S-28 S-28 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,4-dimethylthiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.15 (1H, d, J = 8.0 Hz), 7.86-7.90 (1H, m) 7.70-7.80 (2H, m), 7.45-7.55 (3H, m), 7.16 (1H, d) , J = 7.8 Hz), 6.98 (1H, s), 6.94 (1H, d, J = 7.8 Hz), 4.72 (1H, c, J = 6.4 Hz), 2.80 (2H, t, J = 7.4 Hz), 2.50-2.65 (2H, m), 2.33 (3H, s), 2.27 (3H, s), 1.17-1.63 (15H, m), m / z = 419.

EXAMPLE 176 SYNTHESIS OF S-29 S-29 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol by 2,6-dimethylthiophenol. NMR with H at 400 MHz, 7.21 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 7.05-7.12 (3H, m), 6.83-6.86 (2H, m), 6.73-6.78 (1H, m) , 3.80 (3H, s), 3.69 (1H, c, J = 6.6 Hz), 2.72-2.82 (2H, m), 2.57-2.64 (2H, m), 2.51 (6H, s), 1.32 (3H, d) , J = 6.6 Hz), m / z = 315.

. EXAMPLE 177 SYNTHESIS OF S-30 S-30 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-10 dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 2,6-dimethylthiophenol and 1,3 -dibromopropane. NMR with ^ -H at 400 MHz, 7.22 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 7.05-7.90 (3H, m), 6.84-6.86 (2H, m), 6.74-6.78 (1H, m), 3.80 (3H, s), 3.69 (1H, c, J = 6.6 Hz), 2.62-2.70 (2H, m), 2.51-2.60 (2H, m), 2.50 (6H, s), 1.61-1.70 (2H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 329. fc EXAMPLE 178 SYNTHESIS OF S-31 20 S-31 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2,6-dimethylthiophenol and 1,4-dibromobutane. 25 NMR with E at 400 MHz, 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.04-7.90 (3H, ra), 6.85-6.88 (2H, m), 6.77 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.80 (3H, s), 3.70 (1H, c, J = 6.6 Hz), 2.61 (2H, t, J = 6.7 Hz), 2.51 (6H, s), 2.39-2.48 (2H, m), 1.48-1.58 (4H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 343.

EXAMPLE 179 SYNTHESIS OF S-32 S-32 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 2, 6-dimethylthiophenol and 1,5-dibromopentane NMR with H at 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.06- 7.11 (1H, m), 6.86-6.88 (2H, ra), 6.75-6.79 (1H, m), 3.81 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.61 (2H, t, J = 7.3 Hz), 2.52 (6H, s), 2.38-2.49 (2H, m), 1.34-1.54 (6H, m), 1.33 (3H, d, J = 6.6 -Hz), m / z = 357.

EXAMPLE 180 SYNTHESIS OF S-33 S-33 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,6-dimethylthiophenol and 1, 6 dibromohexane NMR with H at 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.07- 7.11 (3H, m), 6.86-6.88 (2H, m), 6.75-6.79 (1H, m) , 3.81 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.61 (2H, t, J = 7.3 Hz), 2.52 (6H, s), 2.36-2.50 (2H, m), 1.21- 1.54 (8H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 371.

EXAMPLE 181 SYNTHESIS OF S-34 S-34 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,6-dimethylthiophenol and 1, 7- dibromoheptane. NMR with 1H at 400 MHz, 7.20-7.25 (1H, m), 7.07-7.09 (3H, m), 6.86-6.90 (2H, m), 6.75-6.78 (1H, m), 3.81 (3H, s), 3.72 (1H, C, J = 6.6 Hz), 2.61 (2H, t, J = 7.32 Hz), 2.53 (6H, s), 2.36-2.50 (2H, m), 1.20-1.54 (10H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 385.

EXAMPLE 182 SYNTHESIS OF S-35 S-35 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,6-dimethylthiophenol and 1, 8- dibromooctane. NMR with 1H at 400 MHz, 7.20-7.25 (1H, m), 7.05-7.10 (3H, m), 6.88-6.89 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.73 (1H, c, J = 6.5 Hz), 2.61 (2H, t, J = 7.3 Hz), 2.53 (6H, s), 2.37-2.49 (2H, m), 1.20-1.55 (12H, m), 1.35 (3H, d, J = 6.5 Hz), m / z = 399.

EXAMPLE 183 SYNTHESIS OF S-36 S-36 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2, 6-dimethylthiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.15 (1H, d, J = 8.0 Hz), 7.83-7.90 (1H, m) 7.73 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 7.1 Hz) , 7.43-7.52 (3H, m), 7.04-7.12 (3H, m), 4.59 (1H, c, J = 6.6 Hz), 2.77-2.86 (2H, m), 2.70 (2H, t, J = 6.6 Hz), 1.47 (3H, d, J = 6.6 Hz), m / z = 335.

EXAMPLE 184 SYNTHESIS OF S-37 S-37 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,6-dimethylthiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.15 (1H, d, J = 8.0 Hz), 7.84-7.87 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.62 (1H, d, J = 7.1 Hz ), 7.44-7.51 (3H, m), 7.04-7.11 (3H, m), 4.58 (1H, c, J = 6.5 Hz), 2.58-2.73 (4H, m), 2.50 (6H, s), 1.68- 1.75 (2H, m), 1.47 (3H, d, J = 6.5 Hz), m / z = 349.

EXAMPLE 185 SYNTHESIS OF S-38 S-38 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-10 dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy - F ^^ O-benzylmethylamine, respectively, by 2,6-dimethylthiophenol, 1,4-dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.16 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 7.1 Hz ), 7.44-7.52 (3H, 15 m), 7.05-7.11 (3H, m), 4.61 (1H, c, J = 6.5 Hz), 2.61 (2H, t, J = 7.3 Hz), 2.50-2.59 (2H , m), 2.50 (6H, s), 1.50-1.64 (2H, m), 1.48 (3H, d, J = 6.5'Hz), m / z = 363.

EXAMPLE 186 20 SYNTHESIS OF S-39 S-39 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- 25-O-benzylmethylamine, respectively, by 2,6-dimethylthiophenol, 1,5-dibromopentane and (R) - (+) -1- (1-naphthyl) ethylamine.

NMR with 1H at 400 MHz, 8.17 (1H, d, J = 8.0 Hz), 7.85-7-88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 7.1 Hz), 7.44-7.52 (3H, m), 7.06-7.08 (3H, m), 4.61 (1H, c, J = 6.6 Hz), 2.61 (2H, t, J = 7.1 Hz), 2.50-2.58 (2H, m), 2.51 ( 6H, s), 1.35-1.55 (6H, m), 1.48 (3H, d, J = 6.6 Hz), m / z = 377.

EXAMPLE 187 SYNTHESIS OF S-40 S-40 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,6-dimethylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.17 (1H, d, J = 8.0 Hz), 7.85-7.87 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 5.9 Hz ), 7.44-7.52 (3H, m), 7.05-7.09 (3H, m), 4.62 (1H, c, J = 6.5 Hz), 2.50-2.62 (4H, m), 2.52 (6H, s), 1.23-1.53 (8H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 391.

EXAMPLE 188 SYNTHESIS OF S-41 S-41 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,6-dimethylthiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 7.1 Hz ), 7.44-7.53 (3H, m), 7.07-7.09 (3H, m), 4.62 (1H, c, J = 6.6 Hz), 2.50-2.62 (4H, m), 1.20-1.53 (10H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 405.

EXAMPLE 189 SYNTHESIS OF S-42 S-42 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,6-dimethylthiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.15 (1H, d, J = 8.6 Hz), 7.86-7.89 (1H, m) 7.74-7.78 (2H, m), 7.46-7.54 (3H, m), 6.99-7.10 (3H , m), 4.70-4.78 (1H, m), 2.51-2.62 (4H, m), 2.52 (6H, s), 1.07-1.84 (12H, m), 1.59 (3H, d, J = 6.1 Hz), m / z = 419.

EXAMPLE 190 SYNTHESIS OF S-43 S-43 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 3,4-dimethylthiophenol.

NMR with H at 400 MHz, 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.11 (1H, s), 7.00-7.07 (2H, m), 6.80-6.87 (2H, m), 6.75-6.78 (2H, m), 3.79 (3H, s), 3.72 (1H, c, J = 6.5 Hz ), 2.95-2.99 (2H, m), 2. 63-2.70 (2H, m), 2.21 (3H, s), 2.20 (3H, s), 1.33 (3H, d, J = 6.5 Hz), m / z = 315.

EXAMPLE 191 SYNTHESIS OF S-44 S-44 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 3, 4-dimethylthiophenol and 1,3-dibromopropane. NMR with H at 400 MHz, 7.20-7.25 (1H, m), 7.12 (1H, s), 7.01-7.08 (2H, m), 6.84-6.88 (2H, m), 6.75-6.78 (1H, m), 3.80 (3H, s), 3.70 (1H, c, J = 7.0 Hz), 2.83-2.95 (2H, m), 2.50-2.63 (2H, m), 2.22 (3H, s), 2.21 (3H, s) , 1.72-1.77 (2H, m), 1.32 (3H, d, J = 7.0 Hz), m / z = 329.

EXAMPLE 192 SYNTHESIS OF S-45 S-45 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 3,4-dimethylthiophenol and 1,4 - dibromobutane.

NMR with 1H at 400 MHz, 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.11 (1H, s), 7.01-7.07 (2H, m), 6.85-6.87 (2H, m), 6.75-6.78 (1H, m), 3.80 (3H, s), 3.70 (1H, c, J = 7.0 Hz ), 2.84 (2H, t, J = 7.5) Hz), 2.40-2.52 (2H, m), 2.22 (3H, s), 2.21 (3H, s), 1.54-1.65 (4H, m), 1.32 (3H, d, J = 7.0 Hz), m / z = 343.

EXAMPLE 193 SYNTHESIS OF S-46 S-46 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2, 5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 3,4-dimethylthiophenol and 1, 5 -dibromopentane, m / z = 357.

EXAMPLE 194 SYNTHESIS OF S-47 S-47 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 3,4-dimethylthiophenol and 1, 6 dibromohexane NMR with ^ -H at 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.12 (1H, s), 7.02-7.08 (2H, m), 6.86-6.89 (2H, m), 6.75-6.78 (1H, m), 3.81 (3H, s), 3.71 (1H, c, J = 7.0 Hz ), 2.84 (2H, t, J = 7.3 Hz), 2.38-2.50 (2H, m), 2.23 (3H, s), 2.22 (3H, s), 1.56-1.62 (2H, m), 1.24-1.48 ( 6H, m), 1.33 (3H, d, J = 7.0 Hz), m / z = 377.

EXAMPLE 195 SYNTHESIS OF S-48 S-48 was synthesized by almost the same method as 5 was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 3,4-dimethylthiophenol and 1,7 -dibromoheptane. NMR with H at 400 MHz, 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.11 (1H, s), 7.01-7.08 (2H, m), 6.86-6.88 (2H, m), 6.75-6.78 (1H, m), 3.80 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.80 (2H, t, J = 7.5 Hz), 2.38-2.50 (2H, m), 2.22 (3H, s) , 2.21 (3H, s), 1.56-1.62 (2H, m), 1.33-1.45 (4H, m), 1.33 (3H, d, J = 6.5 Hz), 1.24-1.28 (4H, m), m / z = 385.

EXAMPLE 196 SYNTHESIS OF S-49 mk? S-49 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5- 20 dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 3,4-dimethylthiophenol and 1,8. -dibromooctane. NMR with 1H at 400 MHz, 7.21-7.25 (1H, m), 7.02-7.08 (2H, m), 6.87-6.89 (1H, d, J = 8.0 Hz), 6.87 (1H, s), 6.76-6.78 ( 1H, m), 3.80 (3H, s), 3.70-3.74 (1H, m), 2.85 (2H, t, J = 7.8 Hz), 2.38- 25 2.50 (2H, m), 2.22 (3H, s), 2.21 (3H, s), 1.56-1.62 (2H, m), 1.33-1.46 (4H, m), 1.34 (3H, d, J = 7.0 Hz), 1.25 (6H, broad s), m / z 399, EXAMPLE 197 SYNTHESIS OF S-50 S-50 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 3, 4-dimethylthiophenol and (R) - (+) -1- (1-naphthyl) ethylamine.

EXAMPLE 198 SYNTHESIS OF S-51 S-51 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,4-dimethylthiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with XH at 400 MHz, 8.16 (1H, d, J = 8.5 Hz), 8.85 (1H, d, J = 9.0 Hz), 7.72 (1H, d, J = 8.0 Hz), 7.61 (1H, d, J = 7.5 Hz), 7.43-7.49 (3H, m), 7.11 (1H, s), 6.97-7.07 (2H, m), 4.58 (1H, c, J = 6.5 Hz), 2.85-2.97 (2H, m) , 2.61-2.73 (2H, m), 2.22 (6H, s), 1.76-1.82 (2H, m), 1.46 (3H, d, J = 6.5 Hz), m / z = 349.

EXAMPLE 199 SYNTHESIS OF S-52 S-52 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,4-dimethylthiophenol, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.86 (1H, d, J = 9.0 Hz), 8.18 (1H, d, J = 8.5 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.62 (1H, d, J = 7.0 Hz), 7.44-7.51 (3H, m), 7.11 (1H, s), 7.01-7.07 (2H, m), 4.60 (1H, c, J = 6.5 Hz), 2.84 (2H, t, J = 6.8 Hz), 2.50-2.62 (2H, m), 1.60- 1.68 (4H, m), 1.47 (3H, d, J = 6.5 Hz), m / z = 363.

EXAMPLE 200 SYNTHESIS OF S-53 S-53 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,4-dimethylthiophenol, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.17 (1H, d, J = 8.5 Hz), 7.86 (1H, dd, J = 8.0 Hz, J = 1.5 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.62 ( 1H, d, J = 7.0 Hz), 7.44-7.51 (3H, m), 7.11 (1H, s), 7.01-7.09 (2H, m), 4.60 (1H, c, J = 6.5 Hz), 2.84 (2H , t, J = 7.3 Hz), 2.50-2.61 (2H, m), 2.22 (3H, s), 2.24 (3H, s), 1.57-1.63 (2H, m), 1.41-1.53 (4H, m), 1.48 (3H, d, J = 6.5 Hz), m / z = 377.

EXAMPLE 201 SYNTHESIS OF S-54 S-54 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,4-dimethylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 391.

EXAMPLE 202 SYNTHESIS OF S-55 S-55 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,4-dimethylthiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with ^ -H at 400 MHz, 8.18 (1H, d, J = 8.0 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.63 (1H, d , J = 7.5 Hz), 7.39-7.51 (3H, m), 7.11 (1H, s), 7.01-7.07 (2H, m), 4.60 (1H, c, J = 6.5 Hz), 2.83 (2H, t, J = 7.3 Hz), 2.49-2.59 (2H, m), 2.22 (3H, s), 2.20 (3H, s), 1.28-1.62 (10H, m), 1.48 (3H, d, J = 6.5 Hz), m / z = 405 EXAMPLE 203 SYNTHESIS OF S-56 S-56 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,4-dimethylthiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.18 (1H, d, J = 8.0 Hz), 7.87 (1H, d, J = 8.0 Hz), 7.74 (1H, d, J = 8.0 Hz), 7.65 (1H, d, J = 7.5 Hz), 7.45-7.52 (3H, ra), 7.12 (1H, s), 7.02-7.08 (2H, m), 4.63 (1H, C, J = 7.0 Hz), 2.84 (2H, t, J = 7.3 Hz), 2.51-2.62 (2H, m), 2.22 (3H, s), 2.21 (3H, s), 1.56-1.62 (2H, m), 1.50 (3H, d, J = 7.0 Hz), 1.45- 1.52 (2H, m), 1.33-1.42 (2H, m), 1.25-1.28 (6H, m), m / z = 419.

EXAMPLE 204 SYNTHESIS OF S-57 S-57 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol by 3, 5-dimethylthiophenol. NMR with 1H at 400 MHz, 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.96 (2H, s), 6.88-6.91 (2H, m), 6.82 (1H, s), 6.78-6.80 (1H, m), 3.82 (3H, s), 3.76 (1H, c, J = 6.5 Hz), 3.01-3.06 (2H, m), 2.69-2.78 (2H, m), 2.28 (6H, s), 1.36 (3H, d, J = 6.5 Hz), m / z = 315.

EXAMPLE 205 SYNTHESIS OF S-58 S-58 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 3,5-dimethylthiophenol and 1,3-dimethylthiophene. dibromopropane. NMR with 1H at 400 MHz, 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.93 (2H, s), 6.86-6.88 (2H, m), 6.76-6.78 (2H, m), 3.80 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.86-2.98 (2H, m), 2.51-2.65 (2H, m), 2.27 (6H, s), 1.74-1.81 (2H, m ), 1.32 (3H, d, J = 6.5 Hz), m / z = 329.

EXAMPLE 206 SYNTHESIS OF S-59 S-59 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the 1-bromo-2-chloroethane, respectively, by 3,5-dimethylthiophenol and 1,4 - dibromobutane. NMR with H at 400 MHz, 7.22 (1H, dd, J = 7.5 Hz, J = 7.5 Hz), 6.92 (2H, s), 6.86-6.88 (2H, m), 6.75-6.78 (2H, m), 3.80 (3H, s), 3. 71 (1H, c, J = 7.0 Hz), 2.86 (2H, t, J = 7.0 Hz), 2.39-2.54 (2H, m), 2.27 (6H, s), 1.55-1.68 (4H, m), 1.33 (3H, d, J = 7.0 Hz), m / z = 343.

EXAMPLE 207 SYNTHESIS OF S-60 S-60 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 3, 5 -dimethylthiophenol and 1,5-dibromopentane. NMR with H at 400 MHz, 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.92 (2H, s), 6.86-6.88 (2H, m), 6.75-6.78 (2H, m), 3.81 (3H, s), 3. 71 (1H, c, J = 7.0 Hz), 2.87 (2H, t, J = 7.3 Hz), 2.39-2.51 (2H, m), 2.27 (6H, s), 1.58-1.65 (2H, m), 1.40 -1.49 (4H, m), 1.33 (3H, d, J = 7.0 Hz), m / z = 357.

EXAMPLE 208 P SYNTHESIS OF S-61 S-61 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 3,5-dimethylthiophenol and 1,6 -dibromohexane. NMR with H at 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.93 (2H, s), 6.86-6.89 (2H, m), 6.76-6.78 (2H, m), 3.81 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.87 (2H, t, J = 7.3 Hz), 2.39-2.88 (2H, m), 2.27 (6H, s), 1.58-1.65 (2H, m), 1.36-1.49 (4H, m), 1.33 (3H, d, J = 6.5 Hz ), 1.25-1.31 (2H, ra), m / z = 371.

EXAMPLE 209 SYNTHESIS OF S-62 S-62 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 3,5-dimethylthiophenol and 1, 7- dibromoheptane. NMR with H at 400 MHz, 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.93 (2H, s), 6.86-6.89 (2H, m), 6.75-6.78 (2H, m), 3.81 (3H, s), 3.72 (1H, c, J = 7.0 Hz), 2.87 (2H, t, J = 7.5 Hz), 2.38-2.51 (2H, m), 2.72 (6H, s), 1.58-1.64 (2H, m), 1.35-1.47 (4H, m), 1.33 (3H, d, J = 7.0 Hz) , 1.25-1.30 (4H, m), m / z = 385.

EXAMPLE 210 SYNTHESIS OF S-63 S-63 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 3,5-dimethylthiophenol and 1, 8- dibromooctane. NMR with ^ -H at 400 MHz, 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.91 (2H, s), 6.85-6.88 (2H, m), 6.77 (1H, s), 6.74 -6.75 (1H, m), 3.79 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.86 (2H, t, J = 7.5 Hz), 2.37-2.49 (2H, m), 2.26 ( 6H, s), 1.57-1.63 (2H, m), 1.34-1.43 (4H, m), 1.32 (3H, d, J = 6.5 Hz), 1.20-1.30 (6H, m), m / z = 399.

EXAMPLE 211 SYNTHESIS OF S-64 S-64 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 3, 5 -dimethylthiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.15 (1H, d, J = 8.0 Hz), 7.85-7.87 (1H, m) 7.72 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 6.5 Hz) , 7.42-7.52 (3H, m), 6.93 (2H, s), 6.79 (1H, s), 4.61 (1H, c, J = 6.5 Hz), 3.05 (2H, t, J = 6.5 Hz), 2.76- 2.84 (2H, m), 2.24 (6H, s), 1.48 (3H, d, J = 6.5 Hz), m / z = 335.

EXAMPLE 212 SYNTHESIS OF S-65 S-65 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,5-dimethylthiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.18 (1H, d, J = 8.5 Hz), 7.86 (1H, d, J = 7.0 Hz), 7.24 (1H, d, J = 8.5 Hz), 7.63 (1H, d, J = 6.5 Hz), 7.45-7.51 (3H, m), 6.93 (2H, s), 6.78 (1H, s), 4.60 (1H, c, J = 6.5'Hz), 2.89-3.01 (2H, m), 2.63-2.75 (2H, m), 2.26 (6H, s), 1.79-1.85 (2H, m), 1.48 (3H, d, J = 6.5 Hz), m / z = 349.

EXAMPLE 213 SYNTHESIS OF S-66 S-66 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,5-dimethylthiophenol, 1,4-dibromobutane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.86 (1H, d, J = 8.5 Hz), 8.18 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 7.5 Hz), 7.23 (1H, d, J = 8.0 Hz), 7.44-7.51 (3H, m), 6.92 (2H, s), 6.78 (1H, s), 4.61 (1H, c, J = 7.0 Hz), 2.86-2.88 (2H, m), 2.53 -2.64 (2H, m), 2.26 (6H, s), 1.60-1.70 (4H, m), 1.48 (3H, d, J = 7.0 Hz), m / z = 363.

EXAMPLE 214 SYNTHESIS OF S-67 S-67 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,5-dimethylthiophenol, 1,5-dibromopentane and (R) - (+) - 1-ethylamine. NMR with H at 400 MHz, 8.85 (1H, d, J = 7.5 Hz), 8.16 (1H, d, J = 8.5 Hz), 7.72 (1H, d, J = 8.0 Hz) (, 7.61 (1H, d, J = 7.5 Hz), 7.43-7.50 (3H, m), 6.91 (2H, s), 6.77 (1H, s), 4.60 (1H, c, J = 6.5 Hz), 2.85 (2H, t, J = 7.5 Hz), 2.49-2.60 (2H, m), 2.25 (6H, s), 1.58-1.64 (2H, m), 1.41-1.53 (4H, m), 1.47 (3H, d, J = 6.5 Hz), m / z = 377.

EXAMPLE 215 SYNTHESIS OF S I-68 II S-68 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol, l-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 3,5-dimethylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 400 MHz 8.18 (1H, d, J = 8.5 Hz), 7.86 (1H, d, J = 7.5 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 7.5 Hz), 7.46-7.50 (3H, m), 6.92 (2H, s), 6.77 (1H, s), 4.61 (1H, c, J = 6.5 Hz), 2. 86 (2H, t, J = 7.3 Hz), 2.52-2.61 (2H, m), 2.26 (6H, s), 1.57-1.64 (2H, m), 1.45-1.57 (2H, m), 1.48 (3H , d, J = 6.5 Hz), 1.35-1.44 (2H, m), 1.29-1.36 (2H, m), m / z = 391.

EXAMPLE 216 SYNTHESIS OF S-69 S-69 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3,5-dimethylthiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.18 (1H, d, J = 8.0 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 7.5 Hz), 7.42-7.52 (3H, m), 6.92 (2H, s), 6.78 (1H, s), 4.62 (1H, c, J = 7.0 Hz), 2.86 (2H, t, J = 7.3 Hz ), 2.51-2.60 (2H, m), 2.27 (6H, s), 1.79-1.85 (2H, m), 1.57-1.63 (2H, m), 1.49 (3H, d, J = 7.0 Hz), 1.39 ( 2H, broad s), 1.29 (4H, broad s), m / z = 405.

EXAMPLE 217 SYNTHESIS OF S-70 S-70 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Ó-benzylmethylamine, respectively, by 3,5-dimethylthiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.18 (1H, d, J = 8.5 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 7.5 Hz), 7.44-7.52 (3H, m), 6.93 (2H, s), 6.78 (1H, s), 4.62 (1H, c, J = 6.5 Hz), 2.87 (2H, t, J = 7.5 Hz ), 2.50-2.61 (2H, m), 2.27 (6H, s), 1.58-1.64 (2H, m), 1.47-1.52 (2H, m), 1.49 (3H, d, J = 6.5 Hz), 1.35- 1.42 (2H, m), 1.24-1.30 (6H, m), m / z = 419.

EXAMPLE 218 SYNTHESIS OF S-71 S-71 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 4-bromothiophenol. NMR with H at 400 MHz, 7.33-7.37 (2H, m), 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.13-7.16 (2H, m), 6.83-6.87 (2H, m), 6.76-6.79 (1H, m), 3.80 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.99 (2H, t, J = 6.5 Hz), 2.59-2.75 (2H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 365, 367.

EXAMPLE 219 SYNTHESIS OF S-72 S-72 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-bromothiophenol and 1,3-dibromopropane. NMR with XH at 400 MHz, 7.37 (2H, d, J = 8.8 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.15 (2H, d, J = 8.8 Hz), 6.85- 6.88 (2H, m), 6. 78 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.80 (3H, s), 3.71 (1H, c, J = 8.2 Hz), 2.85-2.98 (2H, m ), 2.50-2.65 (2H, m), 1.71-1.81 (2H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 379, 381.

EXAMPLE 220 SYNTHESIS OF S-73 S-73 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-bromothiophenol and 1,4-dibromobutane. NMR at 400 MHz, 7.37 (2H, d, J = 8.5 Hz), 7.23 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 7.15 (2H, ra), 6.75-6.79 (1H, m) , 3.80 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.85 (2H, t, J = 7.1 Hz), 2.39-2.54 (2H, m), 1.51-1.69 (4H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 393, 3.95.

EXAMPLE 221 SYNTHESIS OF S-74 S-74 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-bromothiophenol and 1,5-dibromopentane. NMR with 1H at 400 MHz, 7.37 (2H, d, J = 8.8 Hz), 7.23 (1H, dd, J = 8.2 Hz, J = 8.2 Hz), 7.15 (2H, d, J = 8.8 Hz), 6.86- 6.88 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.86 (2H, t, J = 7.3 Hz), 2.38-2.52 (2H, m), 1.60 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.36-1.51 (4H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 407, 409 EXAMPLE 222 SYNTHESIS OF S-75 S-75 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 4-bromothiophenol and 1,6-dibromohexane. NMR with H at 400 MHz, 7.37 (2H, d, J = 8.6 Hz), 7.23 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 7.15 (2H, d, J = 8.6 Hz), 6.87-6.89 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.72 ( 1H, c, J = 6.6 Hz), 2.86 (2H, t, J = 7.3 Hz), 2.38-2.52 (2H, m), 1.60 (2H, tt, J = 7.2 Hz, J = 7.3 Hz) 1.23-1.50 (6H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 421, 423.

EXAMPLE 223 SYNTHESIS OF S-76 S-76 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-bromothiophenol and 1,7-dibromoheptane.

NMR with 1H at 400 MHz, 7.38 (2H, d, J = 8.5 Hz), 7.23 (1H, dd, J = 8.1 Hz, 'J = 8.1 Hz), 6.87-6.89 (2H, m), 6.78 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.81 (3H, s), 3.73 (1H, c, J = 6.6 Hz), 2.86 (2H, t, J = 7.3 Hz), 2.38 -2.52 (2H, m), 1.60 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.08-1.50 (8H, m), 1.36 (3H, d, J = 6.6 Hz), m / z = 435, 437.

EXAMPLE 224 SYNTHESIS OF S-77 S-77 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 4-bromothiophenol and 1,8-dibromooctane . NMR with H at 400 MHz, 7.35-7.40 (2H, m), 7.23 (1H, d, J = 8.0 Hz), 7.14-7.18 (2H, m), 6.88-6.92 (2H, m), 6.74-6.80 ( 1H, m), 3.81 (3H, s), 3.75 (1H, c, J = 6.7 Hz), 2.86 (2H, t, J = 7.6 Hz), 2.39-2.53 (2H, m), 1.54-1.64 (2H , m), 1.20-1.50 (10H, m), 1.38 (3H, d, J = 6.7 Hz), m / z = 449, 451.

EXAMPLE 225 SYNTHESIS OF S-78 S-78 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 4-bromothiophenol and (R) - (+) -1- (1-naphthyl) ethylamine.

EXAMPLE 226 5 SYNTHESIS OF S-79 S-79 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy -benzylmethylamine, respectively, by 4-bromothiophenol, 1,3- ^ dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz, 8.16 (1H, d, J = 7.8 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.62 (1H, d, J = 6.8 Hz ), 7.44-7.52 (3H, m), 7.32-7.42 (2H, m), 7.10-7.15 (2H, m), 4.60 (1H, c, J = 6.6 Hz), 2.83-3.05 (2H, m), 2.60-2.77 (2H, m), 1.76-1.87 (2H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 399, 401.

EXAMPLE 227 SYNTHESIS OF S-80 20 S-80 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 4-bromothiophenol, 1,4- 25 dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR at 400 MHz, 8.17 (1H, d, J = 7.8 Hz), 7.84-7.88 (1H, m), 7.74 (1H, d, J = 8.28 Hz), 7.62 (1H, d, J = 6.6 Hz) , 7.43-7.52 (3H, m), 7.33-7.37 (2H, m), 7.11-7.16 (2H, m), 4.61 (1H, c, J = 6.5 Hz), 2.85 (2H, d, J = 7.0 Hz ), 2.50-2.64 (2H, m), 1.58-1.68 (4H, m), 1.48 (3H, d, J = 6.5 Hz), m / z = 413.415.

EXAMPLE 228 SYNTHESIS OF S-81 S-81 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-bromothiophenol, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.2 Hz), 7.64 (1H, d, J = 7.3 Hz ), 7.45-7.53 (3H, m), 7.34-7.37 (2H, m), 7.11-7.16 (2H, m), 4.62 (1H, c, J = 6.6 Hz), 2.85 (2H, t, J = 7.3 Hz), 2.49-2.62 (2H, m), 1.40-1.65 (6H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 427.429 EXAMPLE 229 SYNTHESIS OF S-82 S-82 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-bromothiophenol, 1,6-dibromohexane and (R) - (+) -1- (1-naphthyl) ethylamine, EXAMPLE 230 SYNTHESIS OF S-83 S-83 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-bromothiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.30 (1H, broad s), 8.10 (1H, d, J = 8.0 Hz), 7.90 (1H, d, J = 8.1 Hz), 7.82 (1H, d, J = 8.1 Hz), 7.49-7.59 (3H, m), 7.33-7.38 (2H, m), 7.11-7.15 (2H, m), 4.96 (1H, broad s), 2.80 (2H, t, J = 7.3 Hz), 2.54-2.74 (2H, m), 0.95-1.88 (13H, m), m / z = 455, 457.

EXAMPLE 231 SYNTHESIS OF S-84 S-84 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-bromothiophenol, 1,8-dibromooctane and '(R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz, 8.35 (1H, s), 8.13 (1H, d, J = 8.0 Hz), 7.88 (1H, d, J = 8.2 Hz), 7.79 (1H, d, J = 8.3 Hz), 7.45-7.56 (3H, m), 7.33-7.39 (2H, m), 7.12-7.18 (2H, m), 4.82 (1H, broad s), 2.84 (2H, t, J = 7.3 Hz), 2.58-2.64 (2H, m), 1.00-1.74 (15H, m), m / z = 469, 471.

EXAMPLE 232 SYNTHESIS OF S-85 S-85 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-10 dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 4-iodophenol and 1,3-dibromopropane . NMR with H at 400 MHz 7.50-7.54 (2H, m), 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.88 (2H, m), 6.76 (1H, dd, J = 8.0 , J = 2.5 Hz), 6.61-6.65 (2H, m), 3.93-4.00 (1H, m), 3.78 (3H, s), 3.72-3.76 (1H, m), 2.58-2.70 (2H, m), 1.86-1.94 (2H, m), 1.34 (3H, d, J = 7.0 Hz), m / z = 411.

EXAMPLE 233 SYNTHESIS OF S-86 20 S-86 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 4 - Iodophenol and 1,4-dibromobutane. 25 NMR with 1H at 400 MHz 7.50-7.53 (2H, m), 7.22 (1H, dd, J = 3.0 Hz, J = 3.0 Hz), 6.87-6.89 (2H, m), 6.76-6.78 (1H, m) , 6.76-6.78 (1H, m), 6.61-6.64 (2H, m), 3.88 (1H, t, J = 6.8 Hz), 3.80 (3H, s), 3.73 (1H, c, J = 6.8 Hz), 2.46-2.58 (2H, m), 1.72-1.82 (2H, m), 1.55-1.67 (2H, m), 1.34 (3H, d, J = 6.8 Hz), m / z = 425.

EXAMPLE 234 SYNTHESIS OF S-87 S-87 was synthesized by almost the same method as that used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, with 4-iodophenol and 1,5-dibromopentane. NMR with 1H at 400 MHz 7.52 (2H, d, J = 8.5 Hz), 7.20-7.25 (1H, m), 6.87 (2H, s), 6.74-6.80 (1H, m), 6.64 (2H, d, J = 8.0 Hz), 3.88 (2H, t, J = 6.5 Hz), 3.80 (3H, s), 3.72 (1H, c, J = 6.3 Hz), 2.40-2.55 (2H, m), 1.71-1.77 (2H , m), 1.40-1.45 (4H, m), 1.34 (3H, d, J = 6.3 Hz), m / z = 439.

EXAMPLE 235 SYNTHESIS OF S-88 S-88 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-iodophenol and 1,6-dibromohexane NMR with 1H at 400 MHz 7.52 (2H, d, J = 9.0 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.87-6.89 (2H, m), 6.77 (1H, dd, J = 8.0 Hz, J = 2.0 Hz), 6.64 (2H, d, J = 9. O Hz), 3.88 (3H, t, J = 6.5 Hz), 3.81 (3H, s), 3.72 (1H, c, J = 7.0 Hz), 2.41-2.53 (2H, m), 1.71-1.76 (2H, m), 1.46-4.50 (2H, m), 1.39-1.45 (2H, m), 1.31-1.38 (2H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 453.

EXAMPLE 236 SYNTHESIS OF S-89 S-89 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 4-iodophenol and 1, 7-dibromoheptan NMR with XH at 400 MHz 7.52 (2H, d, J = 9.0 Hz), 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.87-6.89 (2H, m), 6.76-6.78 (1H, m), 6.65 (2H, d, J = 8.5 Hz), 3.88 (3H, t, J = 6.5 Hz), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.39-2.51 (2H, m), 1.70-1.76 (2H, m), 1.37- 1.49 (4H, m), 1.34 (3H, d, J = 6.5 Hz), 1.25-1.36 (6H, m), m / z = 467.

EXAMPLE 237 SYNTHESIS OF S-90 S-90 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 4-iodophenol and 1,8-dibromooctane NMR with H at 400 MHz 7.53 (2H, d, J = 8.5 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.87-6.89 (2H, m), 6.75-6.78 (1H, m ), 6.65 (2H, d, J = 8.5 Hz), 3.89 (2H, t, J = 6.8 Hz), 3.81 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.39-2.51 (2H , m), 1.71-1.76 (2H, m), 1.38-1.47 (4H, m), 1.34 (3H, d, J = 6.5 Hz), 1.25-1.35 (6H, m), m / z = 481.

EXAMPLE 238 SYNTHESIS OF S-91 S-91 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-iodophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17-8.19 (1H, m), 7.84-7.87 (1H, m), 7.73 (1H, d, J = 8.0 Hz), 7.61 (1H, d, J = 7.0 Hz), 7.50-7.53 (2H, m), 7. 34-7.49 (3H, m), 6.61 (2H, d, J = 9.0 Hz), 4.63 (1H, c, J = 6.5 Hz), 3.95-4.01 (2H, m), 2.69-2.80 (2H, m), 1.91-1.97 (2H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 431.

EXAMPLE 239 SYNTHESIS OF S-92 S-92 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-iodophenol, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.19 (1H, d, J = 7.5 Hz), 7.86 (1H, d, J = 8.0 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 8.0 Hz), 7.45-7.52 (5H, m), 6.61 (2H, d, J = 7.5 Hz), 4.63 (1H, c, J = 6.5 Hz), 3.88 (2H, t, J = 6.5 Hz), 2.56 -2.69 (2H, m), 1.74-1.84 (2H, m), 1.62-1.68 (2H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 445.

EXAMPLE 240 SYNTHESIS OF S-93 S-93 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-iodophenol, 1,5-dibromopentane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.18 (1H, d, J = 8.0 Hz), 7.86 (1H, d, J = 8.5 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 7.0 Hz), 7.45-7.53 (5H, m), 6.63 (2H, d, J = 8.5 Hz), 4.58-4.64 (1H, m), 3.85-3.88 (2H, m), 2.50-2.65 (2H, m ), 1.70-1.76 (2H, m), 1.40-1.55 (4H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 459.

EXAMPLE 241 SYNTHESIS OF S-94 S-94 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-iodophenol, 1,6-dibromohexane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.18 (1H, d, J = 8.5 Hz), 7.83 (1H, d, J = 7.0 Hz), 7.72 (1H, d, J = 7.5 Hz), 7.64 (1H, d, J = 7.5 Hz), 7.40-7.53 (5H, m), 6.63 (2H, d, J = 9.5 Hz), 4.64 (1H, c, J = 6.5 Hz), 3.87 (2H, t, J = 6.5 Hz), 2.50-2.62 (2H, m), 1.70-1.75 (2H, m), 1.35- 1.60 (6H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 473.

EXAMPLE 242 SYNTHESIS OF S-95 S-95 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-iodophenol, 1,7-dibromoheptane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.5 Hz), 7.87 (1H, d, J = 8.0 Hz), 7.74 (1H, d, J = 7.5 Hz), 7.67 (1H, d, J = 7.0 Hz), 7.45-7.53 (5H, m), 6.64 (2H, d, J = 8.5 Hz), 4.65 (1H, c, J = 7.0 Hz), 3.87 (2H, t, J = 6.8 Hz), 2.51 -2.63 (2H, m), 1.78-1.84 (2H, m), 1.69-1.75 (2H, m), 1.52 (3H, d, J = 7. O Hz), 1.25-1.45 (6H, m), m / z = 487.

EXAMPLE 243 SYNTHESIS OF S-96 S-96 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-iodophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.86 (1H, d, J = 7.5 Hz), 8.18 (1H, d, J = 8.5 Hz), 7.74 (1H, d, J = 8.0 Hz), 7.66 (1H, d, J = 7.5 Hz), 7.45-7.54 (5H, m), 6.65 (2H, d, J = 8.5 Hz), 4.64 (1H, c, J = 6.5 Hz), 3.88 (2H, t, J = 6.8 Hz), 2.51-2.63 (2H, m) , 1.79-1.85 (2H, m), 1.70-1.75 (2H, m), 1.51 (3H, d, J = 6.5 Hz), 1.24-1.43 (8H, m), m / z = 501.

EXAMPLE 244 SYNTHESIS OF S-97 S-97 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 2-naphthalenethiol. m / z = 337.

EXAMPLE 245 SYNTHESIS OF S-98 S-98 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-naphthalenethiol and 1,3-dibromopropane. NMR with E at 400 MHz 7.75-7.77 (1H, m), 7.69-7.73 (3H, m), 7.37-7.48 (3H, m), 7.21 (1H, dd, J = 8.2 Hz, J = 8.2 Hz), 6.85-6.88 (2H, m), 6.75-6.79 (1H, m), 3.79 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.98-3.11 (2H, m), 2.54-2.68 ( 2H, m), 1.78-1.87 (2H, m), 1.32 (3H, d, 'J = 6.6 Hz), m / z = 351.

EXAMPLE 246 SYNTHESIS OF S-99 S-99 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-naphthalenethiol and 1,4-dibromobutane. NMR with 1H at 400 MHz 7.69-7.78 (4H, m), 7.38-7.51 (3H, m), 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.85-6.88 (2H, m), 6.76 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.79 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.99 (2H, t, J = 7.1 Hz), 2.41-2.55 (2H, m), 1.56-1.74 (4H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 365 .

EXAMPLE 247 SYNTHESIS OF S-100 S-100 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2-naphthalenethiol and 1,5-dibromopentane. NMR with H at 400 MHz 7.69-7.78 (4H, m), 7.37-7.51 (3H, m), 7.22 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.88 (2H, m), 6.77 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.80 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.99 (2H, t, J = 7.3 Hz), 2.39-2.52 (2H, m), 1.67 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.41-1.53 (4H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 379.

EXAMPLE 248 SYNTHESIS OF S-101 S-101 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-naphthalenethiol and 1,6-dibromohexane. NMR with H at 400 MHz 7.70-7.78 (4H, m), 7.38-7.47 (3H, m), 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 6.86-6.88 (2H, m), 6.77 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = l .0 Hz), 3.80 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.99 (2H, t, J = 7.3 Hz), 2.37-2.51 (2H, m), 1.67 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.39-1.50 (4H, m), 1.25-1.35 (2H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 393.

EXAMPLE 249 SYNTHESIS OF S-102 S-102 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-naphthalenethiol and 1,7-dibromoheptane. NMR with XH at 400 MHz 7.70-7.78 (4H, m), 7.38-7.47 (3H, m), 7.24 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 6.90-6.95 (2H, m), 6.78-6.81 (1H, m), 3.81 (3H, s), 3.79-3.82 (1H, m), 2.99 (2H, t, J = 7.4 Hz), 2. 41-2.54 (2H, m), 1.66 (2H, tt, J = 7.4 Hz, J = 7.4 Hz), 1.15-1.55 (8H, m), 1.43 (3H, d, J = 6.6 Hz), m / z = 407.

EXAMPLE 250 SYNTHESIS OF S-103 S-103 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-naphthalenethiol and 1,8-dibromooctane. NMR with XH at 400 MHz 7.70-7.78 (4H, m), 7.38-7.47 (3H, m), 7.23 (1H, d, J = 7.8 Hz), 6.88-6.92 (2H, m), 6.78 (1H, ddd, J = 8.3 Hz, J = 2.7 Hz, J = 1.0 Hz), 3.81 (3H, s), 3.76 (1H, c, J = 6.4 Hz), 2.99 (2H, t, J = 7.3 Hz), 2.39-2.52 (2H, m), 1.66 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.15-1.55 (10H, m), m / z = 421, EXAMPLE 251 SYNTHESIS OF S-104 S-104 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2- Naphthalenethiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 357.

EXAMPLE 252 SYNTHESIS OF S-105 S-105 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy-O -benzylmethylamine, respectively, by 2-naphthalenethiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.14-8.16 (1H, m), 7.84-7.88 (1H, m), 7.75-7.77 (2H, m), 7.68-7.76 (3H, m), 7.64 (1H, d, J = 6.6 Hz), 7.36-7.48 (6H, m), 4.61 (1H, c, J = 6.6 Hz), 3.00-3.14 (2H, m), 2.66-2.79 (2H, m), 1.88 (2H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 371.

EXAMPLE 253 SYNTHESIS OF S-106 S-106 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy-O -benzylmethylamine, respectively, by 2-naphthalenethiophenol, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.16 (1H, d, J = 8.1 Hz), 7.84-7.87 (1H, m), 7.74-7.77 (2H, m), 7.68-7.72 (3H, m), 7.63 (1H, d) , J = 7.1 Hz), 7.36-7.51 (6H, m), 4.62 (1H, c, J = 6.6 Hz), 2.98 (2H, t, J = 7.0 Hz), 2.52-2.65 (2H, m), 1.63 -1.76 (4H, m), 1.48 (3H, d, J = 6.6 Hz), m / z = 385.

EXAMPLE 254 SYNTHESIS OF S-107 S-107 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy-O -benzylmethylamine, respectively, by 2-naphtalenethiophenol, 1,5-dibromopentane and (R) - (+) -1- (1-naphthyl) ethylamine.

EXAMPLE 255 SYNTHESIS OF S-108 S-108 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy-O -benzylmethylamine, respectively, by 2-naphthalenethiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.16 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74-7.77 (2H, m), 7.69-7.73 (3H, m), 7.64 (1H, d) , J = 7.1 Hz), 7.38-7.52 (6H, m), 4.62 (1H, c, J = 6.5 Hz), 2.98 (2H, t, J = 7.4 Hz), 2.49-2.62 (2H, m), 1.66 (2H, tt, J = 7.4 Hz, J = 7.4 Hz), 1.27-1.54 (6H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 413.

EXAMPLE 256 SYNTHESIS OF S-109 S-109 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy-O -benzyl-ethylamine, respectively, by 2-naphthalenethiophenol, 1, 7-dibromoheptane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.16 (1H, m), 7.84-7.87 (1H, m), 7.69-7.77 (2H, m), 7.64 (1H, d, J = 6.8 Hz), 7.37-7.53 (6H, m), 4.62 (1H, c, J = 6.6 Hz), 2.98 (2H, t, J = 7.4 Hz) , 2.48-2.62 (2H, m), 1.65 (2H, tt, J = 7.4 Hz, J = 7.4 Hz), 1.25-1.52 (8H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 427.

EXAMPLE 257 SYNTHESIS OF S-110 S-110 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, l-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O -benzylmethylamine, respectively, by 2-naphthalenethiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.14 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.67-7.79 (6H, m), 7.37-7.53 (6H, m), 4.70 (1H, c , J = 6.6 Hz), 2.98 (2H, t, J = 7.3 Hz), 2.50-2.65 (2H, m), 1.65 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.05-1.60 (10H , m), 1.57 (3H, d, J = 6.6 Hz), m / z = 441.

EXAMPLE 258 SYNTHESIS OF S-III S-III was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 2-methoxythiophenol. NMR with H at 400 MHz 7.14-7.22 (3H, m), 6.81-6.89 (4H, m), 6.73-6.76 (1H, m), 3.85 (3H, s), 3.78 (3H, s), 3.71 (1H , c, J = 6.6 Hz), 2.98 (2H, t, J = 6.5 Hz), 2.61-2.73 (2H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 317.

EXAMPLE 259 SYNTHESIS OF S-112 S-112 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-methoxythiophenol and 1,3-dibromopropane. NMR with 1H at 400 MHz 7.21-7.25 (2H, m), 7.14-7.19 (1H, m), 6.82-6.92 (4H, m), 6.77 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.87 (3H, s), 3.80 (3H, s), 3.73 (1H, c, J = 6.6 Hz), 2.85-2.98 (2H, m), 2.52-2.67 (2H, m), 1.73 -1.86 (2H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 331.

EXAMPLE 260 SYNTHESIS OF S-113 S-113 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-methoxythiophenol and 1,4-dibromobutane. NMR with 1H at 400 MHz 7.21-7.25 (2H, m), 7.14-7.19 (1H, m), 6.82-6.93 (4H, m), 6.75-6.79 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz , J = 1.0 Hz), 3.88 (3H, s), 3.80 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.86 (2H, t, J = 7.0 Hz), 2.41-2.55 (2H , m), 1.58-1.71 (4H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 345.

EXAMPLE 261 SYNTHESIS OF S-114 S-114 was synthesized by almost the same method as that used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-methoxythiophenol and 1,5-dibromopentane. NMR with 1H at 400 MHz 7.21-7.26 (2H, m), 7.13-7.18 (1H, m), 6. 82-6.93 (4H, m), 6.76-6.79 (1H, m), 3.88 (3H, s), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.86 (2H, t, J = 7.4 Hz), 2.38-2.52 (2H, m), 1.56-1.67 (2H, m), 1.38-1.53 (4H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 359.

EXAMPLE 262 SYNTHESIS OF S-115 S-115 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-methoxythiophenol and 1,6-dibromohexane. NMR with 1H at 400 MHz 7.19-7.24 (2H, m), 7.12-7.16 (1H, m), 6.81-6.91 (4H, m), 6.74-6.77 (1H, m), 3.86 (3H, s), 3.79 (3H, s), 3.70 (1H, c, J = 6.6 Hz), 2.84 (2H, t, J = 7.5 Hz), 2.36-2.50 (2H, m), 1.57-1.65 (2H, m), 1.23- 1.48 (6H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 373.

EXAMPLE 263 SYNTHESIS OF S-116 S-116 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-methoxythiophenol and 1,7-dibromoheptane. NMR with ^ -H at 400 MHz 7.21-7.27 (2H, m), 7.13-7.18 (1H, m), 6.89-6.97 (4H, m), 6.80-6.95 (1H, m), 3.88 (3H, s) , 3.83 (3H, s), 3.80-3.83 (2H, t, J = 7.3 Hz), 2.85 (1H, m), 2.43-2.56 (2H, m), 1.36-1.66 (6H, m), 1.47 (3H , d, J = 6.2 Hz), 1.18-1.30 (4H, m), m / z = 387.

EXAMPLE 264 SYNTHESIS OF S-117 S-117 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-methoxythiophenol and 1,8-dibromooctane. NMR with 1H at 400 MHz 7.21-7.25 (2H, m), 7.13-7.18 (1H, m), 6. 82-6.94 (4H, m), 6.76-6.79 (1H, m), 3.88 (3H, s), 3.81 (3H, s), 3.73 (2H, t, J = 7.3 Hz), 2.86 (1H, c, J = 6.5 Hz), 2.38-2.52 (2H, m), 1.60-1.70 (2H, m), 1.20-1.60 (10H, m), 1.35 (3H, d, J = 6.5 Hz), m / z = 401.

EXAMPLE 265 SYNTHESIS OF S-118 S-118 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2- methoxythiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with XH at 400 MHz 8.15 (1H, d, J = 7.6 Hz), 7.84-7.87 (1H, m), 7.73 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 6.4 Hz) , 7.40-7.51 (3H, m), 7.24 (1H, dd, J = 7.6 Hz, J = 1.7 Hz), 7.18 (1H, ddd, J = 7.8 Hz, J = 7.8 Hz, J = 1.7 Hz), 6.81 -6.88 (2H, m), 4.62 (1H, c, J = 6.6 Hz), 3.84 (3H, s), 3.05 (2H, t, J = 6.4 Hz), 2.73-2.82 (2H, m), 1.48 ( 3H, d, J = 6.6 Hz), m / z = 337.

EXAMPLE 266 SYNTHESIS OF S-119 S-119 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-methoxythiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.15 (1H, d, J = 7.6 Hz), 7.82-7.86 (1H, m), 7.72 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 6.8 Hz) , 7.43-7.50 (3H, m), 7.21 (1H, 'dd, J = 7.6 Hz, J = 1.5 Hz), 7.14 (1H, ddd, J = 8.0 Hz, J = 8.0 Hz, J = 1.5 Hz ), 6.87 (1H, dd, J = 7.6 Hz, J = 1.2 Hz), 6.81 (1H, dd, J = 8.0 Hz, J = 1 .1 Hz), 4.61 (1H, c, J = 6.6 Hz), 3.84 (3H, s), 2.85-2.99 (2H, m), 2.61-2.77 (2H, m), 1.78-1.86 (2H, m), 1.47 (3H, d, J = 6.6 Hz), m / z = 351 EXAMPLE 267 SYNTHESIS OF S-120 S-120 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-methoxythiophenol, 1,4-dibromobutane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 7.1 Hz) , 7.44-7.52 (3H, m), 7.21 (1H, dd, J = 7.8 Hz, J = 1.6 Hz), 7.13-7.18 (1H, m), 7.14 (1H, ddd, J = 7.6 Hz, J = 7.6 Hz, J = 1.2 Hz), 6.82 (1H, dd, J = 8.3 Hz, J = 1.2 Hz), 4.62 (1H, c, J = 6.5 Hz), 3.86 (3H, s), 2.83-2.88 (2H, m), 2.52-2.65 (2H, m), 1.64-1.70 (4H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 365.

EXAMPLE 268 SYNTHESIS OF S-121 S-121 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-methoxythiophenol, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with ^ -H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.83-7.88 (1H, m), 7.71-7.75 (1H, d, J = 7.0 Hz), 7.41-7.52 (3H, m ), 7.21 (1H, dd, J = 7.6 Hz, J = 1.7 Hz), 7.15 (1H, ddd, J = 7.6 Hz, J = 7.6 Hz, J = 1.7 Hz), 6.90 (1H, ddd, J = 7.6 Hz, J = 7.6 Hz, J = 1.2 Hz), 6.82 (1H, d, J = 8.2 Hz, J = ll Hz), 4.61 (1H, c, J = 6.6 Hz), 3.87 (3H, s), 2.85 (2H, t, J = 7.3 Hz), 2.50-2.62 (2H, m), 1.40-1.48 (6H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 379.

EXAMPLE 269 SYNTHESIS OF S-122 S-122 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-methoxythiophenol, 1,6-dibromohexane and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 393 EXAMPLE 270 SYNTHESIS OF S-123 S-123 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-methoxythiophenol, 1,7-dibromoheptane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.87 (1H, d.J = 7.1 Hz), 7.70-7.78 (2H, m), 7.41-7.51 (3H, m), 7.21 ( 1H, dd, J = 7.6 Hz, J = 1.5 Hz), 7.12-7.17 (1H, m), 6.90 (1H, ddd, J = 7.6 Hz, J = 7.6 Hz, J = 1.2 Hz), 6.80-6.83 ( 1H, m), 4.67-4.75 (1H, m), 3.87 (3H, s), 2.84 (2H, t, J = 7.3 Hz), 2.51-2.64 (2H, m), 1.05-1.64 (13H, m) , m / z = 407.

EXAMPLE 271 SYNTHESIS OF S-124 S-124 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-methoxythiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.16 (1H, d, J = 8.3 Hz), 7.86-7.89 (1H, m), 7. 70-7.78 (2H, m), 7.46-7.55 (3H, m), 7.22 (1H, dd, J = 7.6 Hz, J = 1.7 Hz), 7.13-7.17 (1H, m), 6.87-6.92 (1H, m), 4.70 (1H, broad s), 3.88 (3H, s), 2.85 (2H, t, J = 7.4 Hz), 2.52-2.64 (2H, m), 1.05-1.65 (15H, m), m / z = 421.

EXAMPLE 272 SYNTHESIS OF S-125 S-125 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 3-methoxythiophenol. NMR with XH at 400 MHz 7.22 (1H, d, J = 8.0 Hz), 7.16 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.83-6.89 (4H, m), 6.77 (1H, ddd, J = 8.0 Hz, J = 2.6 Hz, J = 1.0 Hz); 6.71 (1H, ddd, J = 7.5 Hz, J = 2.6 Hz, J = 1.0 Hz), 3.80 (3H, s), 3.78 (3H, s), 3.74 (1H, c, J = 6.5 Hz), 3.02- 3.06 (2H, m), 2.67-2.78 (2H, m), 1.35 (3H, d, J = 6.5 Hz), m / z = 317.

EXAMPLE 273 SYNTHESIS OF S-126 S-126 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 3-methoxythiophenol and 1,3-dibromopropane. NMR with H at 400 MHz 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.89 (3H, m), 6.85 (1H, dd, J = 2.1 Hz, J = 2.1 Hz), 6.78 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.2 Hz), 6.70 (1H, ddd, J = 8.4 Hz, J = 2.7 Hz, J = 1.0 Hz), 3.81 (3H, s), 3.78 (3H, s), 3.72 (1H, c, J = 6.6 Hz) , 2.88-3.02 (2H, m), 2.51-2.66 (2H, m), 1.74-1.87 (2H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 331.

EXAMPLE 274 SYNTHESIS OF S-127 S-127 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 3-methoxythiophenol and 1,4-dibromobutane. NMR with H at 400 MHz 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.89 (3H, m), 6.83-6.84 (1H, m), 6.76-6.79 (1H, m), 6.69 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.81 (3H, s), 3.79 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.89 (2H, t, J = 7.1 Hz), 2.40-2.55 (2H, m), 1.53-1.72 (4H, m), 1.34 (4H, m), m / z = 345.

EXAMPLE 275 SYNTHESIS OF S-128 S-128 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 3-methoxythiophenol and 1,5-dibromopentane. NMR with H at 400 MHz 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.89 (3H, m), 6.84 (1H, dd, J = 4.1 Hz, J = 4.1 Hz), 6.76-6.79 (1H, m), 6.70 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.81 (3H , s), 3.79 (3H, s), 3.72 (1H, c, J = 6.5 Hz), 2.89 (2H, t, J = 7.3 Hz), 2.38-2.52 (2H, m), 1.59- 1.67 (2H, m), 1.37-1.52 (4H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 359.

EXAMPLE 276 SYNTHESIS OF S-129 S-129 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 3-methoxythiophenol and 1,6-dibromohexane. 'NMR with ^ -H at 400 MHz 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.90 (3H, m), 6.83-6.85 (1H, m), 6.76-6.79 (1H, m), 6.69 (1H, ddd, J = 8.3 Hz, J = 2.6 Hz, J = l .0 Hz), 3.81 (3H, s), 3.79 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.89- (2H, t, J = 7.3 Hz), 2.37-2.51 (2H, m) , 1.59-1.67 (2H, m), 1.24- 1.52 (6H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 373.

EXAMPLE 277 SYNTHESIS OF S-130 S-130 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 3-methoxythiophenol and 1,7-dibromoheptane.

NMR with H at 400 MHz 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.90 (3H, m), 6.69 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.81 (3H, s), 3.79 (3H, s), 3.74 (1H, c, J = 6.6 Hz), 2.89 (2H , t, J = 7.3 Hz), 2.38-2.52 (2H, m), 1.58-1.66 (2H, m), 1.19-1.49 (8H, m) 1.37 (3H, d, J = 6.6 Hz), m / z = 387.

EXAMPLE 278 SYNTHESIS OF S-131 S-131 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 3-methoxythiophenol and 1,8-dibromooctane. NMR with H at 400 MHz 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.84-6.85 (1H, m), 6.78 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 0.8 Hz), 6.69 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 0.8 Hz), 3.81 (3H, s), 3.79 (3H, s), 3.73 (1H, c, J = 6.5 Hz), 2.89 (2H, t, J = 7.4 Hz), 2.38-2.52 (2H, m), 1.59-1.70 (2H, m), 1.20-1.50 (10H, m), 1.35 (3H, d, J = 6.5 Hz), m / z = 401.

EXAMPLE 279 SYNTHESIS OF S-132 S-122 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 3- methoxythiophenol and (R) - (+) -1- (1-napl) ethylamine. NMR with H at 400 MHz 8.15 (1H, d, J = 7.8 Hz), 7.85-7.87 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 6.6 Hz) , 7.42-7.55 (3H, m), 7.12-7.16 (1H, m), 6.85-6.89 (2H, m), 6.69-6.72 (1H, m), 4.63 (1H, c, J = 6.5 Hz), 3.76 (1H, s), 3.08 (2H, t, J = 6.4 Hz), 2.76-2.87 (2H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 337.

EXAMPLE 280 SYNTHESIS OF S-133 S-133 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Ó-benzylmethylamine, respectively, by 3-methoxythiophenol, 1,3-dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.18 (1H, d, J = 9.4 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 6.6 Hz) , 7.44-7.52 (3H, m), 7.16 (1H, dd, J = 7.8 Hz, J = 7.8 Hz), 6.84-6.89 (2H, m), 6.68-6.71 (1H, m), 4.61 (1H, c , 3 = 6. 6 Hz), 3.77 (3H, s), 2.91-3.04 (2H, m), 2.62-2.76 (2H, m), 1.80-1.90 (2H, m), 1.48 (3H, d, J = 6.6 Hz), m / z = 351.

EXAMPLE 281 SYNTHESIS OF S-134 S-134 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3-methoxythiophenol, 1,4-dibromobutane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7.73 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 6.84 Hz) , 7.44-7.52 (3H, m), 7.16 (1H, dd, J = 7.8 Hz, J = 7.8 Hz), 6.83-6.88 (2H, m), 6.67-6.70 (1H, m), 4.62 (1H, c , J = 6.6 Hz), 3.77 (3H, s), 2.89 (2H, t, J = 7.1 Hz), 2.51-2.65 (2H, m), 1.59-1.73 (4H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 365.

EXAMPLE 282 SYNTHESIS OF S-135 S-135 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3-methoxythiophenol, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.1 Hz), 7.63 (1H, d, J = 6.6 Hz) , 7.43-7.52 (3H, m), 7.17 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.85-6.88 (1H, m), 6.84 (1H, dd, J = 2.1 Hz, J = 2.1 Hz), 6.69 (1H, ddd, J = 6.7 Hz, J = 2.4 Hz, J = 0.7 Hz), 4.62 (1H, c, J = 6.6 Hz), 3.78 (3H, s), 2.88 (2H, t, J = 7.3 Hz), 2.50-2.63 (2H, m), 1.59-1.67 (2H, m), 1.40-1.55 (4H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 379 .

EXAMPLE 283 SYNTHESIS OF S-136 S-136 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3-methoxythiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.16 (1H, d, .7 = 8.3 Hz), 7.80-7.88 (1H, m), 7.73-7.76 (1H, m), 7.41-7.53 (3H, m), 6.85-6.88 ( 1H, m), 6.83 (1H, dd, J = 2.1 Hz, J = 2.1 Hz), 6.68 (1H, ddd, J = 8.4 Hz, J = 2.4 Hz, J = 0.9 Hz), 4.67 (1H, c, J = 6.6 Hz), 2.87 (2H, t, J = 7.3 Hz), 2.51-2.63 (2H, m), 1.25-1.66 (11H, m) m / z = 393.

EXAMPLE 284 SYNTHESIS OF S-137 S-137 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3-methoxythiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.86-7.89 (1H, m), 7.75-7.80 (2H, m), 7.45-7.55 (3H, m), 7.16 (1H, dd , J = 8.1 Hz, J = 8.1 Hz), 6.82-6.88 (2H, m), 6.68 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = 0.7 Hz), 4.70-4.78 (1H, m ), 3.78 (3H, s), 2.86 (2H, t, J = 7.3 Hz), 2.52-2.65 (2H, m), 1.05-1.65 (13H, m) m / z = 407.

EXAMPLE 285 SYNTHESIS OF S-138 S-138 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 3-methoxythiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.14 (1H, d, J = 8.0 Hz), 7.87-7.89 (1H, m), 7.77 (1H, d, J = 8.0 Hz), 7.47-7.55 (3H, m), 7.17 ( 1H, dd, J = 8.1 Hz, J = 8.1 Hz), 6.83-6.89 (2H, m), 6.68 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = 1.0 Hz), 4.75 (1H, s broad), 3.78 (3H, s), 2.88 (2H, t, J = 7.3 Hz), 2.53-2.66 (2H, m), 1.00-1.75 (15H, m), m / z = 421.

EXAMPLE 286 SYNTHESIS OF S-139 S-139 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol by 4-methoxythiophenol. NMR with 1H at 400 MHz 7.28 (2H, d, J = 8.0 Hz), 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.75-6.88 (5H, m), 3.80 (3H, s) , 3.78 (3H, s), 3.70 (1H, c, J = 6.6 Hz), 2.88-2.93 (2H, m), 2.57-2.70 (2H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 317.

EXAMPLE 287 SYNTHESIS OF S-140 S-140 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-methoxythiophenol and 1,3-dibromopropane. NMR with 1H at 400 MHz 7.31 (2H, d, J = 8.8 Hz), 7.23 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 6.85-6.88 (2H, m), 6.82 (2H, d, J = 8.8 Hz), 6.77 (1H, ddd, J = 8.2 Hz, J = 2.7 Hz, J = 1.0 Hz), 3.80 (3H, s), 3.79 (3H, s), 3.70 (1H, c, J = 6.6 Hz), 2.77-2.89 (2H, m), 2.49-2.64 (2H, m), 1.64-1.80 (2H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 331 EXAMPLE 288 SYNTHESIS OF S-141 S-141 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-methoxythiophenol and 1,4-dibromobutane. NMR with 1H at 400 MHz 7.31 (2H, d, J = 8.8 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.85-6.89 (2H, m), 6.82 (2H, d, J = 8.8 Hz), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.79 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.75-2.80 (2H, m), 2.33-2.53 (2H, m), 1.53-1.62 (4H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 345.

EXAMPLE 289 SYNTHESIS OF S-142 S-142 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-methoxythiophenol and 1,5-dibromopentane. NMR with H at 400 MHz 7.31 (2H, d, J = 8.8 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.85-6.89 (2H, m), 6.83 (2H, d, J = 8.8 Hz), 6.76-6.80 (1H, m), 3.81 (3H, s), 3.79 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.78 (2H, t, J = 7.3 Hz), 2.38-2.52 (2H, m), 1.50-1.60 (2H, m), 1.36-1.50 (4H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 359.

EXAMPLE 290 SYNTHESIS OF S-143 S-143 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-methoxythiophenol and 1,6-dibromohexane. NMR with XH at 400 MHz 7.31 (2H, d, J = 8.8 Hz), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.87-6.90 (2H, m), 6.81-6.85 (2H, m), 6.76-6.80 (1H, m), 3.81 (3H, s), 3.79 (3H, s), 3.73 (1H, c, J = 6.6 Hz), 2.78 (2H, t, J = 7.3 Hz), 2.38-2.51 (2H, m), 1.21-1.59 (8H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 373.

EXAMPLE 291 SYNTHESIS OF S-144 S-144 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-methoxythiophenol and 1,7-dibromoheptane. NMR with 1H at 400 MHz 7.32 (2H, 'd, J = 8.8 Hz), 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.88-6.91 (2H, m), 6.83 (2H, d , J = 8.8 Hz), 6.76-6.80 (1H, m), 3.81 (3H, s), 3.79 (3H, s), 3.75 (1H, c, J = 6.6 Hz), 2.78 (2H, t, J = 7.4 Hz), 2.38-2.52 (2H, m), 1.40-1.60 (4H, m), 1.20-1.30 (4H, m), 1.32-1.40 (2H, m), 1.37 (3H, d, J = 6.6 Hz ), m / z = 387.

EXAMPLE 292 SYNTHESIS OF S-145 S-145 was synthesized by almost the same method as that used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-methoxythiophenol and 1,8-dibromooctane. NMR with 1H at 400 MHz 7.29-7.33 (3H, m), 7.25 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.92-6.99 (2H, m), 6.79-6.85 (2H, m), 3.83 (3H, s), 3.79 (3H, s), 3.81-3.84 (1H, m), 2.78 (2H, t, J = 7.4 Hz), 2.43-2.56 (2H, m), 1.43-1.60 (4H, m), 1.19-1.40 (8H, m), 1.48 (3H, d, J = 5.9 Hz), m / z = 401.

EXAMPLE 293 SYNTHESIS OF S-146 S-146 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 4- methoxythiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with ^ -H at 400 MHz 8.15 (1H, d, J = 7.6 Hz), 7.85-7.89 (1H, m), 7. 73 (1H, d, J = 8.2 Hz), 7.62 (1H, d, J = 6.6 Hz), 7.42-7.52 (3H, m), 7.27-7.30 (2H, m), 6.75-6.80 (2H, m) , 4.61 (1H, c, J = 6.5 Hz), 3.78 (3H, s), 2.97 (2H, t, J = 6.2 Hz), 2.68-2.78 (2H, m), 1. 48 (3H, d, J = 6.5 Hz), m / z = 337.

EXAMPLE 294 SYNTHESIS OF S-147 S-147 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methoxythiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.15 (1H, d, J = 7.8 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 7.1 Hz) , 7.46-7.52 (3H, m), 7.27-7.31 (2H, m), 6.77-6.82 (2H, m), 4.61 (1H, c, J = 6.5 Hz), 3.78 (3H, s), 2.79-2.92 (2H, m), 2.61-2.75 (2H, m), 1.73- 1.81 (2H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 351.

EXAMPLE 295 SYNTHESIS OF S-148 S-148 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methoxythiophenol, 1,4-dibromobutane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.16 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 6.4 Hz) , 7.45-7.53 (3H, m), 7.28-7.31 (2H, m), 6.78-6.82 (2H, m), 4.62 (1H, c, J = 6.4 Hz), 3.78 (3H, s), 2.78 (2H , t, J = 6.7 Hz), 2.49-2.63 (2H, m), 1.46-1.68 (4H, m), 1.49 (3H, d, J = 6.4 Hz), m / z = 365.

EXAMPLE 296 SYNTHESIS OF S-149 S-149 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylphenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methoxythiophenol, 1,5-dibromopentane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.83-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 7.1 Hz) , 7.46-7.53 (3H, m), 7.28-7.32 (2H, m), 6.79-6.83 (2H, m), 4.62 (1H, c, J = 6.6 Hz), 3.78 (3H, s), 2.78 (2H , t, J = 7.3 Hz), 2.48-2.61 (2H, m), 1.46-1.60 (4H, m), 1.49 (3H, d, J = 6.6 Hz), 1.36-1.44 (2H, m), m / z = 379.

EXAMPLE 297 SYNTHESIS OF S-150 S-150 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methoxythiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.82-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.65 (1H, d, J = 7.1 Hz) , 7.41-7.54 (3H, m), 7.28-7.33 (2H, m), 6.80-6.84 (2H, m), 4.63 (1H, c, J = 6.4 Hz), 3.78 (3H, s), 2.75-2.79 (2H, m), 2.49-2.61 (2H, m), 1.24-1.58 (8H, m), m / z = 393.

EXAMPLE 298 SYNTHESIS OF S-151 S-151 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methoxythiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with ^ -H at 400 MHz 8.15 (1H, d, J = 8.0 Hz), 7.86-7.88 (1H, m), 7.71-7.77 (2H, m), 7.46-7.54 (3H, m), 7.29-7.32 (2H, m), 6.80-6.84 (2H, m), 4.69 (1H, broad s), 3.80 (3H, s), 2.77 (2H, t, J = 7.5 Hz), 2.51-2.64 (2H, m) , 1.00-1.64 (13H, ra), m / z = 407.

EXAMPLE 299 SYNTHESIS OF S-152 S-152 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methoxythiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine.

NMR with 1H at 400 MHz 8.15 (1H, d, J = 8.0 Hz), 7.86-7.89 (1H, m), 7.71-7.77 (2H, m), 7.45-7.54 (3H, m), 7.29-7.33 (2H , m), 6.80-6.85 (2H, m), 4.66-4-76 (1H, m), 3.78 (3H, s), 2.78 (2H, t, J = 7.3 Hz), 2.51-2.64 (2H, m ), 1.05-1.56 (15H, m), m / z = 421.

EXAMPLE 300 SYNTHESIS OF S-153 S-153 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 2, 3, 5, 6-tetrafluorothiophenol. NMR with XH at 400 MHz 7.21 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.96-7.06 (1H, m), 6.82-6.86 (2H, m), 6.74-6.77 (1H, m), 3.80 (3H, s), 3.70 (1H, d, J = 6.6 Hz), 3.03 (2H, t, J = 6.0 Hz), 2.55-2.67 (2H, m), 1.34 (3H, d, J = 6.6 Hz ), m / z = 359.

EXAMPLE 301 SYNTHESIS OF S-154 S-154 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrafluorothiophenol and 1,3-dibromopropane. NMR with H at 400 MHz 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 6.97-7.06 (1H, m), 6.84-6.87 (2H, m), 6.74-6.79 (1H, m), 3.81 (3H, s), 3.70 (1H, c, J = 6.6 Hz), '2.90-3.03 (2H, m), 2.49-2.65 (2H, m), 1.66-1.75 (2H, m), 1.33 (3H , d, J = 6.6 Hz), m / z = 373.

EXAMPLE 302 SYNTHESIS OF S-155 S-155 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrafluorothiophenol and 1,4-dibromobutane. NMR with 1H at 400 MHz 7.23 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 6.97-7.06 (1H, m), 6.84-6.88 (2H, m), 6.76-6.78 (1H, m), 3.81 (3H, s), 3.70 (1H, c, J = 6.6 Hz), 2.91 (2H, t, J = 6.6 Hz), 2.37-2.53 (2H, m), 1.53-1.63 (4H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 387.

EXAMPLE 303 SYNTHESIS OF S-156 S-156 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrafluorothiophenol and 1,5-dibromopentane. NMR with H at 400 MHz 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.96-7.05 (1H, m), 6.85-6.89 (2H, m), 6.75-6.79 (1H, m), 3.81 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.91 (2H, t, J = 7.3 Hz), 2.37-2.51 (2H, m), 1.50-1.59 (2H, m), 1.36 -1.46 (4H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 401.

EXAMPLE 304 SYNTHESIS OF S-157 S-157 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrafluorothiophenol and 1, 6-dibromohexane. NMR with 1H at 400 MHz 7.23 (1H, dd, J = 8.1 Hz, J = 8.1 Hz), 6.97-7.06 (1H, m), 6.86-6.89 (2H, m), 6.78-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.91 (2H, t, J = 7.3 Hz), 2.73-2.51 (2H, m), 1.51-1.58 (2H, m), 1.23 -1.49 (6H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 415.

EXAMPLE 305 SYNTHESIS OF S-158 S-158 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrafluorothiophenol and 1, 7-dibromoheptan NMR with -H -H at 400 MHz 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.97-7.05 (1H, m) ', 6.88-6.90 (2H, m), 6.78 (1H, m), 3.81 (3H, s), 3.74 (1H, c, J = 6.7 Hz), 2.91 (2H, t, J = 7.3 Hz), 2.38-2.51 (2H, m), 1.20-1.58 ( 8H, m), 1.36 (3H, d, J = 6.7 Hz), m / z = 429.

EXAMPLE 306 SYNTHESIS OF S-159 S-159 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrafluorothiophenol and 1, 8-dibromooctane NMR with 1H at 400 MHz 7.22-7.26 (1H, m), 6.97-7.05 (1H, m), 6.89-6.92 (2H, m), 6.78-6.81 (1H, m), 3.81 (3H , s), 3.77 (1H, c, J = 6.6 Hz), 2.91 (2H, t, J = 7.4 Hz), 2.40-2.54 (2H, m), 1.17-1.57 (12H, m), 1.40 (3H, d, J = 6.6 Hz), m / z = 443.

EXAMPLE 307 SYNTHESIS OF S-160 S-160 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluorothiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.84-7.89 (1H, m), 7.72 (1H, d, J = 8.3 Hz), 7.61 (1H, d, J = 7.1 Hz) , 7.48 (3H, d, J = 7.1 Hz), 7.43-7.52 (3H, m), 6.75-7.03 (1H, m), 4.61 (1H, c, J = 6.6 Hz), 3.06 (2H, t, J = 6.1 Hz), 2.65-2.75 (2H, m), 1.48 (3H, d, J = 6.6 Hz), m / z = 379.

EXAMPLE 308 SYNTHESIS OF S-161 S-161 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,3,5,6-tetrafluorothiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.16 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.61 (1H, d, J = 6.6 Hz) , 7.44-7.52 (3H, m), 6.95-7.04 (1H, m), 4.60 (1H, c, J = 6.5 Hz), 2.93-3.05 (2H, m), 2.61-2.75 (2H, m), 1.68 -1.78 (2H, m), 1.48 (3H, d, J = 6.5 Hz), m / z = 393.

EXAMPLE 309 SYNTHESIS OF S-162 S-162 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,3,5,6-tetrafluorothiophenol, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.85-7.87 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.62 (1H, d, J = 7.1 Hz) , '7.44-7.52 (3H, m), 6.95-7.04 (1H, m), 4.61 (1H, c, J = 6.6 Hz), 2.90 (2H, t, J = 6.7 Hz), 2.48-2.62 (2H, m), 1.57-1.63 (4H, m), 1.48 (3H, d, J = 6.6 Hz), m / z = 407.

EXAMPLE 310 SYNTHESIS OF S-163 S-163 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,3,5,6-tetrafluorothiophenol, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with XH at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 6.8 Hz) , 7.44-7.52 (3H, m), 6.95-7.04 (1H, m), 4.61 (1H, c, J = 6.6 Hz), 2.90 (2H, t, J = 7.2 Hz), 2.48-2.62 (2H, m ), 1.38-1.58 (6H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 421.

EXAMPLE 311 SYNTHESIS OF S-164 S-164 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,3,5,6-tetrafluorothiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.1 Hz), 7.65 (1H, d, J = 7.1 Hz) , 7.45-7.53 (3H, m), 6.98-7.02 (1H, m), 4.63 (1H, c, J = 6.6 Hz), 2.89 (2H, t, J = 7.3 Hz), 2.47-2.62 (2H, m ), 1.23-1.57 (8H, m), 1.50 (3H, d, J = 6.6 Hz), m / z = 435.

EXAMPLE 312 SYNTHESIS OF S-165 S-165 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,3,5,6-tetrafluorothiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.13 (1H, d, J = 8.3 Hz), 7.87-7.89 (1H, m), 7.78 (2H, d, J = 8.0 Hz), 7.47-7.56 (3H, m), 6.95- 7.04 (1H, m), 4.79 (1H, c, J = 6.4 Hz), 2.87 (2H, t, J = 7.3 Hz), 2.52-2.68 (2H, m), 1.02-1.70 (10H, m), 1.65 (3H, d, J = 6.4 Hz), m / z = 449.

EXAMPLE 313 SYNTHESIS OF S-166 S-166 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,3,5,6-tetrafluorothiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with XH at 400 MHz 8.11 (1H, d, J = 8.5 Hz), 7.88-7.91 (1H, m), 7.80 (1H, d, J = 8.3 Hz), 7.44-7.57 (3H, m), 6.95- 7.03 (1H, m), 4.89 (1H, broad s), 2.88 (2H, t, J = 7.3 Hz), 2.54-2.72 (2H, m), 1.00-1.80 (15H, m), m / z = 463 .

EXAMPLE 314 SYNTHESIS OF S-167 S-167 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 5-chloro-2-mercaptobenzothiazole. NMR with 1H at 400 MHz 7.80 (1H, d, J = 1.7 Hz), 7.63 (1H, dd, J = 8.6 Hz, J = 1.2 Hz), 7.18-7.28 (2H, m), 6.86-6.90 (2H, m), 6.74-6.78 (1H, m), 3.80 (3H, s), 3.77-3.82 (1H, m), 3.43-3.47 (2H, m), 2.85-3.00 (2H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 378.

EXAMPLE 315 SYNTHESIS OF S-168 S-168 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 5-chloro-2-mercaptobenzothiazole and 1, 3 -dibromopropane. NMR with 1H at 400 MHz 7.79 (1H, d, J = 2.0 Hz), 7.63 (1H, d, J = 8.2 Hz), 7.19-7.27 (2H, m), 6.87-6.89 (2H, m), 6.77- 6.79 (1H, m), 3.80 (3H, s), 3.74 (1H, c, J = 6.6 Hz), 3.33-3.47 (2H, m), 2.55-2.72 (2H, m), 1.93-2.00 (2H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 392.

EXAMPLE 316 SYNTHESIS OF S-169 S-169 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 5-chloro-2-mercaptobenzothiazole and 1, 4-dibromobutane. NMR with H at 400 MHz 7.82 (1H, d, J = 2.0 Hz), 7.63 (1H, d, J = 8.5 Hz), 7.21-7.27 (2H, m), 6.87-6.90 (2H, m), 6.76- 6.79 (1H, m), 3.80 (3H, s), 3.73 (1H, c, J = 6.6 Hz), 3.32 (2H, t, J = 7.3 Hz), 2.45-2.60 (2H, m), 1.78-1.90 (2H, m), 1.59-1.65 (2H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 406.

EXAMPLE 317 SYNTHESIS OF S-170 S-170 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 5-chloro-2-mercaptobenzothiazole and 1, 5-dibromopentane. NMR with 1H at 400 MHz 7.83 (1H, d, J = 2.0 Hz), 7.63 (1H, d, J = 7.6 Hz), 7.20-7.27 (2H, m), 6.86-6.87 (2H, m), 6.75- 6.78 (1H, m), 3.81 (3H, s), 3.72 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 3.31 (2H, t, J = 7.3 Hz), 2.41-2.55 (2H , m), 1.80 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.43-1.57 (4H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 420.

EXAMPLE 318 SYNTHESIS OF S-171 S-171 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-brorao-2-chloroethane, respectively, by 5-chloro-2-mercaptobenzothiazole and 1, 6-dibromohexane. NMR with 1H at 400 MHz 7.82-7.83 (1H, m), 7.63 (1H, dd, J = 8.6 Hz, J = 1.7 Hz), 7.19-7.26 (2H, m), 6.88-6.93 (2H, m), 6.75-6.81 (1H, m), 3.82 (3H, s), 3.75-3.83 (1H, m), 3.30 (2H, t, J = 7.3 Hz), 2.42-2.56 (2H, m), 1.79 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.30-1.56 (6H, m), 1.40 (3H, d, J = 6.4 Hz), m / z = 434.

EXAMPLE 319 SYNTHESIS OF S-172 S-172 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 5-chloro-2-mercaptobenzothiazole and 1, 7-dibromoheptane. NMR with 1H at 400 MHz 7.83 (1H, d, J = 2.2 Hz), 7.63 (1H, d, J = 8.3 Hz) 7.24-7.27 (2H, m), 6.89-6.92 (2H, m), 6.77-6.80 (1H, m), 3.81 (3H, s), 3.77 (1H, c, J = 6.6 Hz), 3.31 (2H, t, J = 7.3 Hz), 2.41-2.45 (2H, m), 1.79 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.21-1.55 (8H, m), 1.40 (3H, d, J = 6.6 Hz), m / z = 448.

EXAMPLE 320 SYNTHESIS OF S-173 S-173 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 5-chloro-2-mercaptobenzothiazole and 1, 8-dibromooctane NMR with H at 400 MHz 8.83 (1H, d, J = 1.6 Hz), 7.63 (1H, d, J = 8.5 Hz), 7.22-7.27 (2H, m), 6.91-6.94 (2H, m) , 6.80 (1H, dd, J = 8.3 Hz, J = 2.7 Hz), 3.82 (3H, s), 3.78-3.85 (1H, m), 3.31 (2H, t.J = 8.8 Hz), 2.42-2.53 ( 2H, m), 1.79 (2H, tt, J = 8.8 Hz, J = 8.8 Hz), 1.20-1.57 (10H, m), 1.43 (3H, d, J = 6.3 Hz), m / z = 462.

EXAMPLE 321 SYNTHESIS OF S-174 S-174 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 5- chloro-2-mercaptobenzothiazole and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 398.

EXAMPLE 322 SYNTHESIS OF S-175 S-175 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 5-chloro-2-mercaptobenzothiazole, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.18 (1H, d, J = 7.3 Hz), 7.84-7.88 (1H, m), 7.73-7.76 (2H, m), 7.64 (1H, d, J = 7.8 Hz), 7.62 ( 1H, d, J = 8.3 Hz), 7.43-7.48 (3H, m), 7.23-7.26 (1H, m), 4.63 (1H, c, J = 6.6 Hz), 3.35-3.50 (2H, m), 2.67 -2.82 (2H, m), 2.01 (2H, tt, J = 6.9 Hz, J = 6.9 Hz), 1.50 (3H, d, J = 6.6 Hz), m / z = 412.

EXAMPLE 323 SYNTHESIS OF S-176 S-176 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 5-chloro-2-mercaptobenzothiazole, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.18 (1H, d, J = 8.1 Hz), 7.84-7.87 (1H, m), 8.80 (1H, d, J = 1.9 Hz), 7.73 (1H, d, J = 8.3 Hz) , 7.65 (1H, d, J = 6.8 Hz), 7.62 (1H, d, J = 8.3 Hz), 7.43-7.52 (3H, m), 7.23-7.26 (1H, m), 4.63 (1H, c, J = 6.6 Hz), 3.31 (2H, t, J = 7.2 Hz), 2.56-2.70 (2H, m), 1.82-1.90 (2H, m), 1.68 (2H, tt, J = 7.2 Hz, J = 7.2 Hz ), 1.49 (3H, d, J = 6.6 Hz), m / z = 426.

EXAMPLE 324 SYNTHESIS OF S-177 S-177 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+ ') -3-methoxy -O-benzylmethylamine, respectively, by 5-chloro-2-mercaptobenzothiazole, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.82-7.87 (2H, m), 7.71-7.42 (1H, m), 7.58-7.64 (2H, m), 7.41-7.52 (3H , m), 7.23-7.26 (1H, m), 4.62 (1H, c, J = 6.6 Hz), 3.30 (2H, t, J = 7.3 Hz), 2.51-2.65 (2H, m), 1.79 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.58-1.60 (4H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 440.

EXAMPLE 325 SYNTHESIS OF S-178 S-178 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 5-chloro-2-mercaptobenzothiazole, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with XH at 400 MHz 8.17 (1H, d, J = 8.5 Hz), 7.82-7.88 (2H, m), 7.71-7.75 (1H, m), 7.65 (1H, d, J = 7.1 Hz), 7.62 ( 1H, d, J = 8.5 Hz), 7.42-7.52 (3H, m), 7.23-7.26 (1H, m), 4.63 (1H, c, J = 6.6 Hz), 3.29 (2H, t, J = 7.3 Hz ), 2.51-2.64 (2H, m), 1.78 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.32-1.56 (6H, m), 1.50 (3H, d, J = 6.6 Hz), m / z = 454.

EXAMPLE 326 SYNTHESIS OF S-179 S-179 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 5-chloro-2-mercaptobenzothiazole, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.86-7.88 (1H, m), 7.82.783 (1H, m), 7.72-7.78 (2H, m), 7.62 (1H, dd , J = 8.6 Hz, J = 0.5 Hz), 7.45-7.55 (3H, m), 7.23-7.26 (1H, m), 4.71 (1H, c, J = 6.6 Hz), 3.29 (1H, t, J = 7.3 Hz), 2.50-2.66 (2H, m), 1.71-1.80 (2H, m), 1.58 (3H, d, J = 6.6 Hz), m / z = 468.

EXAMPLE 327 SYNTHESIS OF S-180 S-180 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 5-chloro-2-mercaptobenzothiazole, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7. 83 (1H, d, J = 2.4 Hz), 7.45 (1H, d, J = 8.0 Hz), 7.71 (1H, d, J = 6.8 Hz), 7.62 (1H, d, J = 8.6 Hz), 7.45-7.54 (1H, m), 7.23-7.24 (1H, m), 4.70 (1H, c, J = 6.6 Hz), 3.30 (2H, t, J = 7.3 Hz), 2.52- 2.65 (2H, m), 1.68-1.84 (2H, m), 1.56 ( 3H, d, J = 6.6 Hz), 1.06-1.59 (10H, m), m / z = 482.

EXAMPLE 328 SYNTHESIS OF S-181 S-181 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine. NMR with 1H at 400 MHz 7.23 (1H, d, J = 8.0 Hz), 6.84-6.87 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.69 (1H, c, J = 6.6 Hz), 3.06 -3.19 (2H, m), 2.50-2.66 (2H, m), 1.69 (2H, tt, J = 7.0 Hz, J = 7.0 Hz), 1.33 (3H, d, J = 6.6 Hz ), m / z = 424, 426.

EXAMPLE 329 SYNTHESIS OF S-182 S-182 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrachloro- 4-mercaptopyridine and 1,3-dibromopropane. m / z = 438, 440.

EXAMPLE 330 SYNTHESIS OF S-183 S-183 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine and 1,4-dibromobutane. m / z = 452, 454.

EXAMPLE 331 SYNTHESIS OF S-184 S-184 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6"-tetrachlor -4-mercaptopyridine and 1, 5-dibromopentane, NMR with H at 400 MHz 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.88 (2H, m), 6.76-6.79 (1H, m ), 3.05 (2H, t, J = 7.3 Hz), 3.81 (3H, s), 3.71 (1H, c, J = 6.5 Hz), 2.38-2.52 (2H, m), 1.55 (2H, tt, J = 7.1 Hz, J = 7.1 Hz), 1.36-1.50 (4H, m), 1.34 (3H, d, J = 6.5 Hz), m / z = 466, 468.

EXAMPLE 332 SYNTHESIS OF S-185 S-185 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrachloro- 4-mercaptopyridine and 1,6-dibromohexane. NMR with 1H at 400 MHz 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.86-6.89 (2H, m), 6.76-6.81 (1H, m), 3.81 (3H, s), 3.72 ( 1H, c, J = 6.6 Hz), 3.05 (2H, t, J = 7.3 Hz), 2.37-2.52 (2H, m), 1.55 (2H, tt, J = 7.2 Hz, J = 7.2 Hz), 1.23- 1.49 (6H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 480, 482.

EXAMPLE 333 SYNTHESIS OF S-186 S-186 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrachloro- 4-mercaptopyridine and 1,7-dibromoheptane. NMR with 1H at 400 MHz 7.24 (1H, dd, J = 8.2 Hz, J = 8.2 Hz), 6.87-6.90 (2H, m), 6.76-6.81 (1H, m), 3.81 (3H, s), 3.72 ( 1H, c, J = 6.6 Hz), 3.05 (2H, t, J = 7.3 Hz), 2.38-2.51 (2H, m), 1.55 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.20- 1.49 (8H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 494, 496.

EXAMPLE 334 SYNTHESIS OF S-187 S-187 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 3, 5, 6-tetrachloro- 4-mercaptopyridine and 1,8-dibromooctane. NMR with 1H at 400 MHz 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.88-6.90 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.73 ( 1H, dd, J = 6.6 Hz), 3.06 (2H, t J = 7.3 Hz), 2.39-2.53 (2H, m), 1.55 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.20- 1.50 (10H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 508, 510.

EXAMPLE 335 SYNTHESIS OF S-188 S-188 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 444, 446.

EXAMPLE 336 SYNTHESIS OF S-189 S-189 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with XH at 400 MHz 8.17 (1H, d, J = 7.8 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.69 (1H, d, J = 6.8 Hz) , 7.44-7.52 (3H, m), 4.60 (1H, c, J = 6.5 Hz), 3.08-3.21 (2H, m), 2.62-2.75 (2H, m), 1.69-1.76 (2H, m), 1.49 (3H, d, J = 6.5 Hz), m / z = 458, 460.

EXAMPLE 337 SYNTHESIS OF S-190 S-190 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.40 (1H, d, J = 8.0 Hz), 7.82-7.88 (1H, m), 7.69-7.75 (2H, m), 7.43-7.51 (3H, m), 4.04 (1H, c , J = 6.6 Hz), 2.47-2.70 (4H, m), 1.78-1.82 (4H, m), 1.53 (3H, d, J = 6.6 Hz), m / z = 472, 474.

EXAMPLE 338 S NTESIS OF S-191 S-191 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with -H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.75 (1H, d, J = 8.0 Hz), 7.66 (1H, d, J = 6.8 Hz ), 7.45-7.53 (3H, m), 4.64 (1H, c, J = 6.6 Hz), 3.03 (2H, t, J = 7.2 Hz), 2.49-2.63 (2H, m), 1.35-1.60 (9H, m), m / z = 486, 488.

EXAMPLE 339 SYNTHESIS OF S-192 S-192 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.16 (1H, d, J = 8.0 Hz), 7.86-7.89 (1H, m), 7.76 (1H, d, J = 8.3 Hz), 7.70 (1H, broad s), 7.46-7.54 (3H, m), 4.69 (1H, broad s), 3.02 (2H, t, J = 7.2 Hz), 2.51-2.64 (2H, m), 1.25-1.60 (11H, m), m / z = 500, 502 EXAMPLE 340 SYNTHESIS OF S-193 S-193 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.86-7.89 (1H, m), 7.70-7.78 (1H, m), 7.46-7.55 (3H, m), 4.74 (1H, s) broad), 3.03 (2H, t, J = 7.2 Hz), 2.50-2.66 (2H, m), 1.05-1.65 (13H, m), m / z = 514, 516.

EXAMPLE 341 SYNTHESIS OF S-194 S-194 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrachloro-4-mercaptopyridine, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.86-7.89 (1H, m), 7.72-7.78 (2H, m), 7.46-7.54 (3H, m), 4.72 (1H, c , J = 7.2 Hz); 3. 04 (2H, t, J = 7.2 Hz), 2.52-2.57 (2H, m), 1.00-1.56 (12H, m), 1. 58 (3H, d, J = 6.2 Hz), m / z = 528, 530.

EXAMPLE 342 SYNTHESIS OF S-195 S-195 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluoro-4-trifluoromethyl-thiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 447.

EXAMPLE 343 SYNTHESIS OF S-196 S-196 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluoro-4-trifluoromethylthiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.16 (1H, d, J = 8.0 Hz), 7.84-7.86 (1H, m), 7.73 (1H, d, J = 8.0 Hz), 7.60 (1H, d, J = 6.8 Hz) , 7.43-7.51 (3H, m), 4.59 (1H, c, J = 6.2 Hz), 3.02-3.15 (2H, m), 2.60-2.74 (2H, m), 1.67-1.77 (2H, m), 1.48 (3H, d, J = 6.2 Hz), m / z = 461.

EXAMPLE 344 SYNTHESIS OF S-197 S-197 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) '-3-methoxy -O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluoro-4-trifluoromethylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with ^ -H at 400 MHz 8.17 (1H, d, J = 8.2 Hz), 7.85-7.88 (1H, m), 7.75 (1H, d, J = 8.3 Hz), 7.66 (1H, d, J = 6.8 Hz), 7.45-7.53 (3H, m), 4.64 (1H, c, J = 6.4 Hz), 2.99 (2H, t, J = 7.3 Hz), 2.50-2.63 (2H, m), 1.48-1.60 (4H , m), 1.52 (3H, d, J = 6.4 Hz), 1.26-1.42 (4H, m), m / z = 503.

EXAMPLE 345 SYNTHESIS OF S-198 S-198 was synthesized by almost the same method that was used for the synthesis of S-l, but replacing 2,5-dimethylthiophenol, l-bromo-2-chloroethane and '(R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluoro- 4-trifluoromethylthiophenol, 1,7-dibromoheptane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.75 (1H, d, J = 8.0 Hz), 7.66 (1H, d, J = 6.8 Hz) , 7.45-7.52 (3H, m), 4.65 (1H, c, J = 6.4 Hz), 3.00 (2H, t, J = 7.4 Hz), 2.50-2.63 (2H, m), 1.47-1.60 (4H, m ), 1.52 (3H, d, J = 6.4 Hz), 1.23-1.41 (6H, m), m / z = 517.

EXAMPLE 346 SYNTHESIS OF S-199 S-199 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluoro-4-trifluoromethylthiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.16 (1H, d, J = 8.3 Hz), 7.86-7.88 (1H, m), 7.75 (1H, d, J = 8.3 Hz), 7.69 (1H, d, J = 6.1 Hz) , 7.45-7.53 (3H, m), 4.67 (1H, c, J = 6.4 Hz), 3.01 (2H, t, J = 7.3 Hz), 2.51-2.64 (2H, m), 1.20-1.70 (15H, m ), m / z = 531.

EXAMPLE 347 SYNTHESIS OF S-200 S-200 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluoro-4-trifluoromethylthiophenol, 1, 10-dibromodecane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.51-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 7.1 Hz) , 7.44-7.52 (3H, m), 4.62 (1H, c, J = 6.6 Hz), 3.02 (2H, t, J = 7.4 Hz), 2.50-2.62 (2H, m), 1.54-1.62 (2H, m ), 1.49 (3H, d, J = 6.6 Hz), 1.00-1.54 (14H, m), m / z = 559.

EXAMPLE 348 SYNTHESIS OF S-201 S-201 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2, 3, 5, 6-tetrafluoro-4-trifluoromethylthiophenol, 1, 12-dibromododecane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.3 Hz) 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.66 (1H, d, J = 7.1 Hz), 7.45-7.53 (3H, m), 4.64 (1H, c, J = 6.6 Hz), 3.03 (2H, t, J = 7.4 Hz), 2.50-2.63 (2H, m), 1.20-1.63 (18H, m) , 1.51 (3H, d, J = 6.6 Hz), m / z = 587.

EXAMPLE 349 SYNTHESIS OF S-202 S-202 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2- isopropylthiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.16 (1H, d, J = 7.8 Hz), 7.84-7.87 (1H, m,), 7.72 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 7.1 Hz ), 7.41-7.54 (3H, m), 7.23-7.27 / 2H, m), 7.13-7.16 (1H, m), 7.03-7.07 (1H, m), 4.63 (1H, c, J = 6.5 Hz), 3.45-3.54 (1H, m), 3.04 (2H, t, J = 6.2 Hz), 2.81 (2H, t, J = 6.8 Hz), 1.48 (2H, d, J = 6.5 Hz), 1.19-1.22 (6H , m), m / z = 349.

EXAMPLE 350 SYNTHESIS OF S-203 S-203 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Q £-benzylmethylamine, respectively, by 2-isopropylthiophenol, 1,3-dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 7.8 Hz), 7.86 (1H, d, J = 7.8 Hz), 7.73 (1H, d, J = 8.0 Hz), 7.63 (1H, d, J = 7.3 Hz), 7.43-7.51 (3H, m), 7.22-7.29 (2H, m), 7.08-7.17 (2H, m), 4.60 (1H, c, J = 6.4 Hz), 3.42-3.50 (1H, m ), 2.87-3.00 (2H, m), 2.62-2.76 (2H, m), 1.79-1.86 (2H, m), 1.48 (3H, d, J = 6.4 Hz), 1.18-1.22 (6H, m), m / z '= 463.

EXAMPLE 351 SYNTHESIS OF S-204 S-204 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Ot-benzylmethylamine, respectively, by 2-isopropylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.85-7.87 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 6.8 Hz) , 7.44-7.51 (3H, m), 7.22-7.27 (2H, m), 7.07-7.18 (2H, m), 4.61 (1H, c, J = 6.5 Hz), 3.44-3.53 (1H, m), 2.85 (2H, t, J = 6.8 Hz), 2.51-2.65 (2H, m), 1.63-1.70 (4H, m), 1.48 (3H, d, J = 6.5 Hz), 1.21 (6H, d, J = 6 , 8 Hz), m / z = 377.

EXAMPLE 352 SYNTHESIS OF S-205 S-205 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2, 5-dimethylthiophenol, l-bromo-2-chloroethane and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 2-isopropylthiophenol, 1,5-dibromopentane and (R) - (+ ) -1- (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = .1 Hz ), 7.44-7.52 (3H, m), 7.22-7.28 (2H, m), 7.08-7.18 (2H, m), 4.61 (1H, c, J = 6.5 Hz), 3.42-3.53 (1H, m), 2.85 (2H, t, J = 7.3 Hz), 2.49-2.62 (2H, m), 1.59-1.67 (2H, m), 1.40-1.56 (4H, m), 1.48 (3H, d, J = 6.5 Hz) , 1.21 (6H, d, J = 6.8 Hz), m / z = 391.

EXAMPLE 353 SYNTHESIS OF S-206 S-206 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- QC-benzylmethylamine, respectively, by 2-isopropylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7. 73 (1H, d, J = 8.3 Hz), 7.64 (1H, d, J = 6.8 Hz), 7.41-7.52 (3H, m), 7.21-7.29 (2H, m), 7.09-7.17 (2H, m) , 4.62 (1H, c, J = 6.5 Hz), 3.43-3.53 (1H, m), 2.84 (2H, t, J = 7.3 Hz), 2.49-2.62 (2H, m), 1.58-1.66 (2H, m ), 1.45-1.55 (2H, m), 1.25-1.45 (4H, m), 1.49 (3H, m), 1.21-1.23 (6H, m), m / z = 405.

EXAMPLE 354 SYNTHESIS OF S-207 S-207 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-isopropylthiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7. 74 (1H, d, J = 8.0 Hz), 7.65 (1H, d, J = 7.1 Hz), 7.44-7.52 (3H, m), 7.22-7.29 (2H, m), 7.09-7.17 (2H, m) , 4.63 (1H, c, J = 6.6 Hz), 3.43-3.54 (1H, m), 2.85 (2H, t, J = 7.4 Hz), 2.49-2.62 (2H, m), 1.57-1.65 (2H, m ), 1.36-1.55 (4H, m), 1.49 (3H, d, J = 6.6 Hz), 1.25-1.30 (4H, m), 1.20-1.25 (6H, m), m / z = 419.

EXAMPLE 355 SYNTHESIS OF S-208 • S-208 was synthesized by almost the same method as 5 was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) -3- methoxy-O-benzylmethylamine, respectively, by 2-isopropylthiophenol, 1,8-dibromooctane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.18 (1H, d, J = 8.5 Hz), 7.85-7.88 (1H, m), 10 7.74 (1H, d, J = 8.0 Hz), 7.65 (1H, d, J = 7.1 Hz ), 7.44-7.53 (3H, • m), 7.23-7.29 (2H, m), 7.09-7.17 (2H, m), 4.63 (1H, c, J = 6.6 Hz), 3.43-3.54 (1H, m), 2.85 (2H, t, J) = 7.4 Hz), 2.50-2.62 (2H, m), 1.58-1.67 (4H, m), 1.24-1.52 (10H, m), 1.50 (3H, d, J = 6.6 Hz), 1.22 (6H, d, J = 6.8 Hz), m / z = 433. 15 EXAMPLE 356 SYNTHESIS OF S-209 S-209 was synthesized by almost the same method as 20 was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol by 2, 4, 5-trichlorothiophenol. NMR with H at 400 MHz 7.44 (1H, s), 7.29 (1H, s), 7.23 (1H, dd, J = 8.3 Hz, J = 8.3 Hz), 6.87-6.89 (2H, m), 6.76-6.79 ( 1H, m), 3.80 (3H, s), 3.76 (1H, c, J = 6.6 Hz), 3.03 (2H, t, J = 6.5 Hz), 2.70- 25 2.85 (2H, m), 1.36 (3H, d, J = 6.6 Hz), m / z = 389, 391.

EXAMPLE 357 SYNTHESIS OF S-210 S-210 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the 1-bromo-2-chloroethane, respectively, by 2, 4, 5-trichlorothiophenol and 1, 3 -dibromopropane. NMR with 1H at 400 MHz 7.44 (1H, s), 7.30 (1H, s), 7.22-7.25 (1H, m), 6.87-6.90 (2H, m), 6.77-6.80 (1H, m), 3.81 (3H , s), 3.74 (1H, c, J = 6.5 Hz), 2.89-3.03 (2H, m), 2.54-2.70 (2H, m), 1.77-1.85 (2H, m), 1.36 (3H, d, J = 6.5 Hz), m / z = 403, 405.

EXAMPLE 358 S NTESIS OF S-211 S-211 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,4,5-trichlorothiophenol and 1, 4-dibromobutane. NMR with 1H at 400 MHz 7.44 (1H, s), 7.21-7.26 (2H, m), 6.87-6.91 (2H, m), 6.76-6.80 (2H, m), 3.81 (3H, s), 3.73 (1H , c, J = 6.6 Hz), 2.89 (2H, t, J = 7.3 Hz), 2.39-2.53 (2H, m), 1.64-1.71 (2H, m), 1.39-1.48 (4H, m), 1.25- 1.37 (6H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 459, 461.

EXAMPLE 359 SYNTHESIS OF S-212 S-212 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 4, 5-trichlorothiophenol and 1, 5-dibromopentane. NMR with 400 MHz 7.44 (1H, s), 7.21-7.26 (2H, m), 6.87-6.90 (2H, m), 6.76-6.79 (1H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 2.89 (2H, t, J = 7.3 Hz), 2.41-2.55 (2H, m), 1.64-1.71 (2H, m), 1.43-1.56 (4H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 431, 433.

EXAMPLE 360 SYNTHESIS OF S-213 S-213 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 4, 5-trichlorothiophenol and 1, 6-dibromohexane. NMR with E at 400 MHz 7.44 (1H, s), 7.21-7.26 (2H, m), 6.87-6.90 (2H, m), 6.76-6.79 (2H, m), 3.81 (3H, s), 3.72 (1H , c, J = 6.6 Hz), 2.88 (2H, t, J = 7.3 Hz), 2.39-2.53 (2H, m), 1.63-1.71 (2H, m), 1.28-1.52 (6H, m), 1.34 ( 3H, d, J = 6.6 Hz), m / z = 445, 447.

EXAMPLE 361 SYNTHESIS OF S-214 S-214 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2, 4, 5-trichlorothiophenol and 1, 7-dibromoheptane. NMR with H at 400 MHz 7.44 (1H, s), 7.21-7.26 (2H, m), 6.87-6.91 (2H, m), 6.76-6.80 (2H, m), 3.81 (3H, s), 3.73 (1H , c, J = 6.6 Hz), 2.89 (2H, t, J = 7.3 Hz), 2.39-2.53 (2H, m), 1.64-1.71 (2H, m), 1.39-1.48 (4H, m), 1.25- 1.37 (6H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 459, 461.

EXAMPLE 362 SYNTHESIS OF S-215 S-215 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2,4,5-trichlorothiophenol and 1, 8-dibromooctane. NMR with H at 400 MHz 7.44 (1H, s), 7.25 (1H, s), 7.24 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 6.87-6.90 (2H, m), 6.76-6.80 ( 1H, m), 3.81 (3H, s), 3.73 (1H, c, J = 6.6 Hz), 2.89 (2H, t, J = 7.3 Hz), 2.38-2.52 (2H, m), 1.64-1.71 (2H , m), 1.40-1.50 (4H, m), 1.35 (3H, d, J = 6.6 Hz), 1.25-1.35 (6H, m), m / z = 473, 735.

EXAMPLE 363 SYNTHESIS OF S-216 S-116 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Ót-benzylmethylamine, respectively, by 2,4,5-trichlorothiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.20 (1H, d, J = 8.0 Hz), 7.85-7.88 (1H, m), 7.75 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 7.1 Hz) , 7.45-7.52 (3H, m), 7.4 (1H, s), 7.29 (1H, s), 4.63 (1H, c, J = 6.5 Hz), 2.90- 3.05 (2H, m), 2.64-2.80 (2H , m), 1.81-1.89 (2H, m), 1.52 (3H, d, J = 6.5 Hz), m / z = 423, 425.

EXAMPLE 364 SYNTHESIS OF S-217 S-217 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Ot-benzylmethylamine, respectively, by 2,4,5-trichlorothiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.86-7.88 (1H, m), 7.75 (1H, d, J = 8.3 Hz), 7.66 (1H, d, J = 6.8 Hz) , 7.45-7.53 (3H, m), 7.44 (1H, s), 7.23 (1H, s), 4.65 (1H, c, J = 6.6 Hz), 2.86 (2H, t, J = 7.3 Hz), 2.51- 2.66 (2H, m), 1.30-1.73 (8H, m), 1.52 (3H, d, J = 6.6 Hz), m / z = 465, 467.

EXAMPLE 365 SYNTHESIS OF S-218 S-218 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- C-benzylmethylamine, respectively, by 2,4,5-trichlorothiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.86-7.88 (1H, m), 7.75 (1H, d, J = 8.3 Hz), 7.68 (1H, d, J = 6.6 Hz) , 7.45-7.53 (3H, m), 7.43 (1H, s), 7.24 (1H, s), 4.66 (1H, c, J = 6.4 Hz), 2.87 (2H, t, J = 7.3 Hz), 2.51- 2.64 (2H, m), 1.25-1.70 (10H, m), 1.53 (3H, d, J = 6.4 Hz), m / z = 423, 425.

EXAMPLE 366 SYNTHESIS OF S-219 S-219 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- OC-benzylmethylamine, respectively, by 2,4,5-trichlorothiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.86-7.89 (1H, m), 7. 75 (1H, d, J = 8.3 Hz), 7.68 (1H, broad s), 7.45-7.53 (3H, m), 7. 44 (1H, s), 7.24 (1H, s), 4.67 (1H, broad s), 2.88 (2H, t, J = 7.3 Hz), 2.51-2.64 (2H, m), 1.23-1.71 (15H, m), m / z = 493, 495.

EXAMPLE 367 10 SYNTHESIS OF S-220 I S-220 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 15. 6-ethoxy-2-mercaptobenzothiazole and 1,3-dibromopropane. m / z = 402.

EXAMPLE 368 SYNTHESIS OF S-221 S-221 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the l-bromo-2-chloroethane, respectively, by 6-ethoxy-2-mercaptobenzothiazole and 1 , 4-dibromobutane. NMR with -H at 400 MHz 7.71 (1H, d, J = 8.8 Hz), 7.20-7.24 (2H, m), 6.98 (1H, dd, J = 9.0 Hz, J = 2.4 Hz), 6.87-6.89 (2H, m), 6.77 (1H, ddd, J = 8.0 Hz, J = 2.4 Hz, J = 1.0 Hz) , 4.06 (2H, c, J = 6.9 Hz), 3.80 (3H, s), 3.28 (2H, t, J = 7.5 Hz), 2.45-2.61 (2H, m), 1.75-1.88 (2H, m), 1.58-1.70 (2H, m), 1.44 (3H, t, J = 7.5 Hz), 1.35 (3H, d, J = 6.9 Hz), m / z = 416.

EXAMPLE 369 SYNTHESIS OF S-222 S-222 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 6-ethoxy-2-mercaptobenzothiazole and 1, 5-dibromopentane. NMR with l-H at 400 MHz 7.23 (1H, d, J = 8.8 Hz), 7.20-7.25 (2H, m), 6. 99 (1H, dd, J = 8.8 Hz, J = 2.4 Hz), 6.87-6.90 (2H, m), 6. 16-6. 11 (1H, m), 4.03-4.11 (2H, m), 3.81 (3H, s), 3.72 (1H, c, J = 6.6 Hz), 3.27 (2H, t, J = 7.6 Hz), 2.41-2.54 (2H, m), 1.74-1.82 (2H, m), 1.41-1.56 (4H, m), 1.44 () 3H, t, J = 6.8 Hz), 1.34 (3H, d, J = 6.6 Hz), m / z = 430.

EXAMPLE 370 SYNTHESIS OF S-223 S-223 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 6-ethoxy-2-mercaptobenzothiazole and 1, 6-dibromohexane. NMR with -H at 400 MHz 7.73 (1H, d, J = 9.0 Hz), 7.20-7.25 (2H, m), 6.99 (1H, dd, J = 8.8 Hz, J = 2.4 Hz), 6.88-6.90 (2H , m), 6.77 (1H, ddd, J = 8.3 Hz, J = 2.4 Hz, J = 1.0 Hz), 4.06 (2H, c, J = 7.0 Hz), 3.81 (3H, s), 3.73 (1H, c, J = 6.0 Hz), 3.27 (2H, t, J = 7.3 Hz), 2.40-2.53 (2H, m), 1.74-1.81 (2H, m), 1.25-1.53 (6H, m), 1.44 (3H, t, J = 7.0 Hz), 1.35 (3H, d, J = 6.0 Hz), m / z = 444.

EXAMPLE 371 SYNTHESIS OF S-224 S-224 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 6-ethoxy-2-mercaptobenzothiazole and 1, 7-dibromoheptane. NMR with 400 MHz 7.72 (1H, d, J = 9.0 Hz), 7.25 (1H, dd, J = 6.9 Hz, J = 6.9 Hz), 7.21 (1H, d, J = 2.4 Hz), 6.98 (1H, dd, J = 9.0 Hz, J = 2.4 Hz), 6.78-6.82 (1H, m), 4.06 (3H, c, J = 7.0 Hz), 3.82 (3H, s), 3.79-3.85 (1H, m), 3.27 (2H, t, J = 7.3 Hz), 2.43-2.56 (2H, m), 1.73-1.80 (2H, m), 1.18-1.57 (11H, m), 1.44 (3H, t, J = 7.0 Hz) , m / z = 458.

EXAMPLE 372 SYNTHESIS OF S-225 S-225 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 6-ethoxy-2-mercaptobenzothiazole and 1, 8-dibromooctane. NMR with -H at 400 MHz 7.23 (1H, d, J = 8.8 Hz), 7.21-7.24 (2H, m), 6. 99 (1H, dd, J = 8.8 Hz, J = 2.7 Hz), 6.87-6.91 (2H, m), 6.76-6.80 (1H, m), 4.06 (2H, c, J = 7.0 Hz), 3.81 (3H, s), 3.75 (1H, c, J = 6.6 Hz), 3.28 (2H, t, J = 7.3 Hz), 1.99 -2.53 (2H, m), 1.74-1.81 (2H, m), 1.24-1.48 (10H, m), 1.44 (3H, t, J = 7.0 Hz), 1.37 (3H, d, J = 6.6 Hz), m / z = 472.

EXAMPLE 373 S NTESIS OF S-226 S-226 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-QL-benzylmethylamine, respectively, by 6- ethoxy-2-mercaptobenzothiazole and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 408.

EXAMPLE 374 SYNTHESIS OF S-227 S-227 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Ot-benzylmethylamine, respectively, by 6-ethoxy-2-mercaptobenzothiazole, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 422.

EXAMPLE 375 SYNTHESIS OF S-228 S-228 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Ót-benzylmethylamine, respectively, by 6-ethoxy-2-mercaptobenzothiazole, 1,4-dibromobutane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.18 (1H, d, J = 8.3 Hz), 7.84-7.88 (1H, m), 7.73 (1H, d, J = 8.3 Hz), 7.70 (1H, d, J = 9.0 Hz) , 7.65 (1H, d, J = 7.1 Hz), 7.44-7.52 (3H, m), 7.20 (1H, d, J = 2.4 Hz), 6.97 (1H, dd, J = 9.0 Hz, J = 2.4 Hz) , 4.63 (1H, c, J = 6.6 Hz), 4.05 (2H, c, J = 7.0 Hz), 3.28 (2H, dt, J = 9.2 Hz, J = 1.2 Hz), 2.55-2.69 (2H, m) , 1.81-1.90 (2H, m), 1.63-1.72 (2H, m), 1.50 (3H, d, J = 6.6 Hz), 1.43 (3H, t, J = 7.0 Hz). m / z = 436.

EXAMPLE 376 SYNTHESIS OF S-229 S-229 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Orybenzylmethylamine, respectively, by 6-ethoxy-2-mercaptobenzothiazole, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine.

NMR with H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.83-7.88 (1H, m), 7.73 (1H, d, J = 8.0 Hz), 7.72 (1H, d, J = 8.8 Hz) , 7.64 (1H, d, J = 7.3 Hz), 7.44-7.52 (3H, m), 7.20 (1H, d, J = 2.4 Hz), 6.98 (1H, dd, J = 9.0 Hz, J = 2.7 Hz) , 4.62 (1H, c, J = 6.5 Hz), 4.06 (2H, c, J = 7.0 Hz), 3.27 (2H, t, J = 7.3 Hz), 2.52-2.65 (2H, m), 1.70-1.82 ( 2H, m), 1.49 (3H, d, J = 6.5 Hz), 1.44 (3H, t, J = 7.0 Hz), 1.41-1.60 (4H, m), m / z = 450.

EXAMPLE 377 SYNTHESIS OF S-230 S-230 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- or? -benzylmethylamine, respectively, by 6-ethoxy-2-mercaptobenzothiazole, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.17 (1H, d, J = 8.5 Hz), 7.82-7.88 (1H, m), 7.71-7.75 (2H, m), 7.66 (1H, d, J = 7.0 Hz), 7.41- 7.53 (3H, m), 7.20 (1H, d, J = 2.7 Hz), 6.98 (1H, dd, J = 8.8 Hz, J = 2.7 Hz), 4.64 (1H, c, J = 6.4 Hz), 4.05 ( 2H, c, J = 7.0 Hz), 3.26 (2H, t, J = 7.3 Hz), 2.50-2.64 (2H, m), 1.73-1.81 (2H, m), 1.30-1.55 (6H, m), 1.51 (3H, d, J = 6.4 Hz), 1.43 (3H, t, J = 7.0 Hz), m / z = 464.

EXAMPLE 378 SYNTHESIS OF S-231 S-231 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- OC-benzylmethylamine, respectively, by 6-ethoxy-2-mercaptobenzothiazole, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 1"H at 400 MHz 8.15 (1H, d, J = 8.3 Hz), 7.86-7.88 (1H, m), 7.72-7.78 (2H, m), 7.72 (1H, d, J = 9.1 Hz), 7.45-7.55 (3H, m), 6.98 (1H, dd, J = 8.8 Hz, J = 2.4 Hz), 4.72 (1H, c, J = 6.4 Hz), 4.05 (2H, c, J = 7.0 Hz), 3.25 (2H, t, J = 7.3 Hz), 2.52-2.66 (2H, m), 1.64-1.82 (2H, m), 1.59 (3H, d, J = 6.4 Hz), 1.43 (3H, t, J = 7.0 Hz), 1.03-1.68 (8H, m), m / z = 478.

EXAMPLE 379 SYNTHESIS OF S-232 S-232 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- OC-benzylmethylamine, respectively, by 6-ethoxy-2-mercaptobenzothiazole, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.16 (1H, d, J = 8.5 Hz), 7.86-7.88 (1H, m), 7.68-7.76 (3H, m), 7.45-7.53 (3H, m), 7.21 (1H, d) , J = 2.4 Hz), 6.98 (1H, dd, J = 8.8 Hz, J = 2.4 Hz), 4.67 (1H, c, J = 6.4 Hz), 4.06 (2H, c, J = 7.0 Hz), 3.27 ( 2H, t, J = 7.4 Hz), 2.51-2.64 (2H, m), 1.69-1.80 (2H, m), 1.54 (3H, d, J = 6.4 Hz), 1.43 (3H, t, J = 7.0 Hz ), 1.20-1.60 (10H, m), m / z = 492.

EXAMPLE 380 SYNTHESIS OF S-233 S-233 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-G __-benzylmethylamine, respectively, by 2, 4-dichlorothiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 375.

EXAMPLE 381 SYNTHESIS OF S-234 S-234 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2,4-dichlorothiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with -H at 400 MHz 8.18 (1H, d, J = 7.6 Hz), 7.84-7.89 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 7.1 Hz ), 7.45-7.56 (3H, m), 7.34-7.56 (1H, m), 7.33-7.34 (2H, m), 4.62 (1H, c, J = 6.6 Hz); 2.88-3.04 (2H, m), 2.63-2.78 (2H, m), 1.79-1.87 (2H, m), 1.50 (3H, d, J = 6.6 Hz), m / z = 389. • EXAMPLE 382 SYNTHESIS OF S-225 S-235 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-10 dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy - Q-benzylmethylamine, respectively, by 2,4-dichlorothiophenol, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with 400 MHz 8.18 (1H, d, J = 8.0 Hz), 7.86-7.88 (1H, m), 7.75 (1H, broad s), 7.67 (1H, broad s), 7.45-7.53 (3H, m) , 7.35-7.36 (1H, m), 7.13-7.14 (2H, m), 4.61-4.69 (1H, m), 2.84-2.89 (2H, m), 2.52-2.68 (2H, m), 1.48-1.73 ( 7H, m), m / z = 403.

EXAMPLE 383 SYNTHESIS OF S-236 20 S-136 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol, l-bromo-2-chloroethane and (R) - (+) - 3-methoxy-Otbencylmethylamine, respectively, by 2,4-dichlorothiophenol, 1, 5-dibromopentane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.17 (1H, d, J = 8.0 Hz), 7.86-7.88 (1H, m), 7.75 (1H, d, J = 8.3 Hz), 7.65 (1H, d, J = 7.1 Hz) , 7.45-7.53 (3H, m), 7.35-7.37 (1H, m), 7.14-7.16 (2H, m), 4.64 (1H, d, J = 6.4 Hz), 2.87 (2H, t, J = 7.3) , 2.51-2.64 (2H, m), 1.60-1.68 (2H, m), 1.42-1.58 (4H, m), 1.51 (3H, d, J = 6.4 Hz), m / z = 417.

EXAMPLE 384 SYNTHESIS OF S-237 S-237 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- QC-benzylmethylamine, respectively, by 2,4-dichlorothiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.20 (1H, d, J = 8.0 Hz), 7.84-7.87 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.66 (1H, d, J = 7.1 Hz) , 7.44-7.52 (3H, m), 7.19-7.25 (2H, m), 7.03 (2H, dd, J = 8.5 Hz, J = 2.4 Hz), 4.62 (1H, c, J = 6.6 Hz); 2.90-3.06 (2H, m), 2.62-2.80 (2H, m), 1.86 (2H, tt, J = 7.0 Hz, J = 7.0 Hz), 1.50 (3H, d, J = 6.6 Hz), m / z = 389.

EXAMPLE 385 SYNTHESIS OF S-238 S-238 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- G ^ benzylmethylamine, respectively, by 2,5-dichlorothiophenol, 1,6-dibromohexane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with 400 MHz 8.18 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.73 (1H, d, J = 8.0 Hz), 7.64 (1H, d, J = 6.8 Hz), 7.44-7.53 (3H, m), 7.23-7.26 (1H, m), 7.14 (1H, d, J = 2.4 Hz), 7.03 (1H, d, J = 8.6 Hz, J = 2.4 Hz), 4.63 (1H , c, J = 6.5 Hz); 2.87 (2H, t, J = 7.3 Hz), 2.51-2.64 (2H, m), 1.68 (1H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.30-1.56 (6H, m), 1.50 (3H , d, J = 6.5 Hz), m / z = 431.

EXAMPLE 386 SYNTHESIS OF S-239 S-239 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- Qf-benzylmethylamine, respectively, by 2,5-dichlorothiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.16 (1H, d, J = 8.3 Hz), 7.86-7.88 (1H, m), 7.75 (1H, d, J = 8.0 Hz), 7.70 (1H, d, J = 7.1 Hz) , 7.45-7.53 (3H, m), 7.23 (1H, s), 7.14 (1H, d, J = 2.4 Hz), 7.03 (1H, d, J = 2.4 Hz, J = 6.3 Hz), 4.68 (1H, c, J = 6.4 Hz), 2.87 (2H, t, J = 7.3 Hz), 2.50-2.65 (2H, m), 1.66 (2H, tt, J = 7.3 Hz, J = 7.3 Hz), 1.55 (3H, d, J = 6.4 Hz), 1.05-1.60 (8H, m), m / z = 445.

EXAMPLE 387 SYNTHESIS OF S-240 S-240 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- C &amprbenzylmethylamine, respectively, by 2, 5-dichlorothiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with -H at 400 MHz 8.16 (1H, d, J = 8.3 Hz), 8.85-8.88 (2H, m), 7.75 (1H, d, J = 8.3 Hz), 7.70 (1H, d, J = 7.1 Hz ), 7.45-7.54 (3H, m), 7.24 (1H, s), 7.14 (1H, d, J = 2.4 Hz), 7.02 (1H, dd, J = 8.5 Hz, J = 2.4 Hz), 4.69 (1H , c, J = 6.5 Hz), 2.86 (2H, t, J = 6.8), 2.51-2.65 (2H, m), 1.66 (2H, tt, J = 6.8 Hz, J = 6.8 Hz), 1.55 (3H, d, J = 6.5 Hz), 1.03-1.55 (10H, m), m / z = 459.

EXAMPLE 388 SYNTHESIS OF S-241 S-241 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-CX-benzylmethylamine, respectively, by 4- trifluoromethoxythiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 391.

EXAMPLE 389 SYNTHESIS OF S-242 S-242 was synthesized by almost the same method as 5 was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy - O-benzylmethylamine, respectively, by 4-trifluoromethoxythiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. 10 NMR with H at 400 MHz 8.16-8.20 (1H, m), 7.82-7.89 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.62 (1H, d, J = 6.6 Hz), 7.44-7.52 (3H, m), 7. 27-2.30 (2H, m), 7.08-7.11 (2H, m), 4.61 (1H, c, J = 6.6 Hz), 2. 88-3.05 (2H, m), 2.61-2.76 (2H, m), 1.77-1.85 (2H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 405. 15 EXAMPLE 390 SYNTHESIS OF S-243 i S-243 was synthesized by almost the same method as 20 was used for the synthesis of Sl, but replacing 2,5-dimethylthiophenol, l-bromo-2-chloroethane and (R) - (+) -3-methoxy-O-benzylmethylamine, respectively, by 4-trifluoromethoxythiophenol, 1,7-dibromoheptane and (R) - (+) - 1 - (1-naphthyl) ethylamine. 25 NMR with H at 400 MHz 8.10 (1H, d, J = 8.3 Hz), 7.78-7.81 (1H, m), 7.66 (1H, d, J = 8.3 Hz), 7.57 (1H, d, J = 6.8 Hz ), 7.37-7.45 (3H, m), 7.21-7.24 (2H, m), 7.03-7.05 (2H, m), 4.55 (1H, c, J = 6.6 Hz), 2.80 (2H, t, J = 7.3 Hz), 2.41-2.55 (2H, m), 1.49-1.57 (2H, m), 1.18-1.45 (8H, m), 1.42 (3H, d, J = 6.6 Hz), m / z = 461.

EXAMPLE 391 SYNTHESIS OF S-244 S-244 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-trifluoromethoxythiophenol, 1,8-dibromooctane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with -H at 400 MHz 8.17 (1H, d, J = 8.3 Hz), 7.85-7.88 (1H, m), 7.74 (1H, d, J = 8.0 Hz), 7.65 (1H, d, J = 7.1 Hz ), 7.44-7.53 (3H, m), 7.28-7.33 (3H, m), 7.28-7.33 (2H, m), 7.10-7.13 (2H, ra), 4.64 (1H, c, J = 6.6 Hz), 2.87 (2H, t, J = 7.4 Hz), 2.49-2.62 (2H, m), 1.56-1.65 (2H, m), 1.46-1.55 (2H, m), 1.50 (3H, d, J = 6.6 Hz) , 1.33-1.42 (2H, m), 1.23-1.30 (6H, m), m / z = 475.

EXAMPLE 392 SYNTHESIS OF S-245 S-245 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 2-chlorobenzyl mercaptan.

NMR with lH at 400 MHz 7.33-7.38 (1H, m), 7.28-7.31 (1H, m), 7.47-7.26"(3H, m), 6.87-6.88 (2H, m), 6.78 (1H, ddd, J = 8.1 Hz, J = 2.4 Hz, J = 1.0 Hz), 3.81 (3H, s), 3.77 (2H, s), 3.70 (1H, c, J = 6.5 Hz), 2.57-2.73 (4H, m), 1.33 (3H, d, J = 6.5 Hz), m / z = 335.

EXAMPLE 393 SYNTHESIS OF S-246 S-246 was synthesized by almost the same method as that used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-chlorobenzylmercaptan and 1,3-dibromopropane. NMR with -H at 400 MHz 7.32-7.37 (2H, m), 7.14-7.25 (3H, m), 6.86-6.88 (2H, m), 6.77 (1H, ddd, J = 8.3 Hz, J = 2.7 Hz, J = l .0 Hz), 3.80 (3H, s), 3.71 (1H, c, J = 6.6 Hz), 2.44-2.61 (4H, m), 1.70-1.78 (2H, m), 1.32 (3H, d , J = 6.6 Hz), m / z = 349.

EXAMPLE 394 SYNTHESIS OF S-247 S-247 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-chlorobenzylmercaptan and 1,5-dibromopentane. NMR with lH at 400 MHz 7.32-7.36 (2H, m), 7.14-7.27 (3H, m), 6.88-6.89 (2H, m), 6.76-6.79 (1H, m), 3.81 (2H, s), 3.73 (1H, c, J = 6.6 Hz), 2.38-2.51 (4H, m), 1.30-1.60 (6H, m), 1.35 (3H, d, J = 6.6 Hz), m / z = 377.

EXAMPLE 395 SYNTHESIS OF S-248 S-248 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-chlorobenzylmercaptan and 1,6-dibromohexane. NMR with lH at 400 MHz 7.33-7.36 (2H, m), 7.14-7.27 (3H, m), 6.87-6.90 (2H, m), 6.74-6.79 (1H, m), 3.81 (5H, s), 3.72 (1H, c, J = 6.6 Hz), 2.37-2.51 (4H, m), 1.56 (2H, tt, J = 7.3 Hz, J = 7.3"Hz), 1.40-1.49 (2H, m), 1.20-1.38 (4H, m), 1.34 (3H, d, J = 6.6 Hz), m / z = 391.

EXAMPLE 396 SYNTHESIS OF S-249 S-249 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and (R) - (+) - 3-methoxy-benzylmethylamine, respectively, by 2-chlorobenzyl mercaptan and ( R) - (+) -1- (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.16 (1H, d, J = 8.0 Hz), 7.85-7.87 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.65 (1H, d, J = 6.8 Hz) , 7.44-7.53 (3H, m), 7.24-7.34 (2H, m), 7.13-7.18 (2H, m), 4.60 (1H, c, J = 6.6 Hz), 3.77 (2H, s), 2.63-2.78 (4H, m), 1.48 (3H, d, J = 6.6 Hz), m / z = 355. EXAMPLE 397 SYNTHESIS OF S-250 S-250 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and (R) - (+) - 3-methoxy-O-benzylethylamine, respectively, by 2-chlorobenzyl mercaptan , 1,3-dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.16 (1H, d, J = 8.3 Hz), 7.84-7.88 (1H, m), 7.74 (1H, d, J = 8.3 Hz), 7.63 (1H, d, J = 6.8 Hz) , 7.44-7.52 (3H, m), 7.28-7.34 (2H, m), 7.12-7.18 (2H, m), 4.62 (1H, c, J = 6.6 Hz), 3.79 (2H, s), 2.45-2.72 (4H, m), 1.75-1.81 (2H, m), 1.49 (3H, d, J = 6.6 Hz), m / z = 369.

EXAMPLE 398 SYNTHESIS OF S-251 S-251 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol by 4-chlorobenzyl mercaptan. NMR with XH at 400 MHz 7.21-7.26 (3H, m), 7.15-7.19 (2H, m), 6. 85-6.87 (2H, m), 6.76-6.80 (1H, m), 3.81 (3H, s), 3.68 (1H, c, J = 6.6 Hz), 3.58 (2H, d, J = 2.0 Hz), 2.49 -2.67 (4H, m), 1.33 (3H, d, J = 6.6 Hz), m / z = 335.

EXAMPLE 399 SYNTHESIS OF S-252 S-252 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 4-chlorobenzylmercaptan and 1,3-dibromopropane. NMR with lH at 400 MHz 7.19-7.27 (5H, m), 6.85-6.87 (2H, m), 6.76-6.79 (1H, m), 3.80 (3H, s), 3.69 (1H, c, J = 6.6 Hz ), 3.63 (2H, s), 2.35-2.59 (4H, m), 1.63-1.-73 (2H, m), 1.32 (3H, d, J = 6.6 Hz), m / z = 349.

EXAMPLE 400 SYNTHESIS OF S-253 S-253 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-Ot-benzylmethylamine, respectively, by 4 - chlorobenzylmercaptan and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 355.

EXAMPLE 401 SYNTHESIS OF S-254 S-254 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy-O -benzylethylamine, respectively, by 4-chlorobenzylmercaptan, 1,3-dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.17 (1H, d, J = 2.1 Hz), 7.85-7.88 (1H, m), 7.73-7.75 (1H, d, J = 8.1 Hz), 7.62 (1H, d, J = 7.4 Hz), 7.45-7.53 (3H, m), 7.17-7.25 (4H, m), 4.60 (1H, c, J = 6.6 Hz), 3.61 (2H, s), 2.55-2.71 (2H, m), 2.37 -2.48 (2H, m), 1.70-1.78 (2H, m), 1.48 (3H, d, J = 6.6 Hz), m / z = 369.

EXAMPLE 402 SYNTHESIS OF S-255 S-255 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-quinolinothiol and 1,4-dibromobutane. NMR with -H at 400 MHz 7.83-7.88 (2H, m), 7.69 (1H, d, J = 8.0 Hz), 7.59-7.63 (1H, m), 7.37-7.41 (1H, m), 7.15-7.24 ( 2H, m), 6.86-6.90 (2H, m), 6.73-6.78 (1H, m), 3.78 (3H, m), 3.73 (1H, c, J = 6.8 Hz), 3.30 (2H, t, J = 6.8 Hz), 2.47-2.61 (2H, m), 1.58-1.84 (4H, m), 1.33 (3H, d, J = 6.8 Hz), m / z = 366.

EXAMPLE 403 SYNTHESIS OF S-256 S-256 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and l-bromo-2-chloroethane, respectively, by 2-quinolinothiol and 1,5-dibromopentane. NMR with lH at 400 MHz 7.90 (1H, d, J = 8.4 Hz), 7.85 (1H, d, J = 8.4 Hz), 7.67-6.70 (1H, m), 7.60-7.64 (1H, m), 7.38- 7.42 (1H, m), 7.22 (1H, dd, J = 6.2 Hz, J = 6.2 Hz), 7.18 (1H, d, J = 8.4 Hz), 6.86-6.90 (2H, m), 6.75-6.78 (1H , m), 3.80 (3H, s), 3.74 (1H, c, J = 6.4 Hz), 3.32 (2H, t, J = 7.4 Hz), 2.40-2.55 (2H, m), 1.76 (2H, tt, J = 7.4 Hz, J = 7.4 Hz), 1.44-1.59 (4H, m), 1.34 (3H, d, J = 6.4 Hz), m / z = 380.

EXAMPLE 404 SYNTHESIS OF S-257 S-257 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and 1-bromo-2-chloroethane, respectively, by 2-quinolinothiol and 1,6-dibromone. NMR with l-H at 400 MHz 7.91 (1H, d, J = 8.2 Hz), 7.85 (1H, d, J = 8.8 Hz), 7.70 (1H, dd, J = 8.0 Hz, J = 1.2 Hz), 7.61-7.64 (1H, m), 7.38-7.43 (1H, m), 7.23 (1H, dd, J = 8.0 Hz, J = 8.0 Hz), 7.18 (1H, d, J = 8.4 Hz), 6.88-6.90 (2H, m), 6.76-6.79 (1H, m), 3.80 (3H, s), 3.74 (1H, c, J = 6.4 Hz), 3.34 (2H, t, J = 7.2 Hz), 2.41-2.54 (2H, m), 1.78 (2H, tt, J = 7.2 Hz, J = 7.2 Hz), 1.41-1.54 (4H, m) , 1.35 (3H, d, J = 6.4 Hz), m / z = 394.

EXAMPLE 405 SYNTHESIS OF S-258 S-258 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-quinolinothiol, 1,3-dibromopropane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.18 (1H, d, J = 8.0 Hz), 7.83-7.87 (3H, m), 7.73 (1H, d, J = 8.0 Hz), 7.65-7.70 (2H, m), (1H , d, J = 7.1 Hz), 7.56-7.60 (1H, m), 7.43-7.52 (3H, m), 7.37-7.42 (1H, m), 7.17 (1H, d, J = 8.8 Hz), 4.65 ( 1H, c, J = 6.4 Hz), 3.32 (2H, t, J = 7.2 Hz), 2.59-2.75 (2H, m), 1.67-1.87 (4H, m), 1.49 (3H, d, J = 6.4 Hz ), m / z = 386.

EXAMPLE 406 SYNTHESIS OF S-259 S-259 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 2-quinolinothiol, 1,5-dibromopentane and (R) - (+) -1- (1-naphthyl) ethylamine. NMR with l-H at 400 MHz 8.16 (1H, d, J = 8.0 Hz), 7.83-7.92 (3H, m), I 7.58-7.74 (4H, m), 7.37-7.52 (4H, m), 7.18 (1H, d, J = 8.4 Hz), 4.63 (1H, c, J = 6.4 Hz), 3.32 (2H, t, J = 7.4 Hz), 2.54-2.66 (2H, m), 1.40-1.82 (6H, m), 1.49 (3H, d, J = 6.4 Hz), m / z = 400.

EXAMPLE 407 SYNTHESIS OF S-260 S-260 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy - O-benzylmethylamine, respectively, by 2-quinolinothiol, 1,6-dibromone and (R) - (+) - 1 - (1-naphthyl) ethylamine. 15 NMR with 400 MHz 8.17 (1H, d, J = 8.4 Hz), 7.37-7.87 (11H, m), 7.18 (1H, d, J = 8.8 Hz), 4.60-4.70 (1H, m), 3.30 ( 2H, t, J = 7.4 Hz), 2.46-2.83 (4H, m), 1.20-1.77 (9H, m), m / z = 414.

EXAMPLE 408 20 SYNTHESIS OF S-261 S-261 was synthesized by almost the same method that was used for the synthesis of S-1, but replacing the 2,5-dimethylthiophenol and the (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 4-methylthiophenol and (R) - (+) - 1 - (1-naphthyl) ethylamine.

NMR with -H at 400 MHz 8.13-8.16 (1H, m), 7.83-7.89 (1H, m), 7.72 (1H, d, J = 8.4 Hz), 7.62 (1H, d, J = 6.8 Hz), 7.41-7.52 (3H, m), 7. 21 (2H, d, J = 8.0 Hz), 7.02-7.05 (2H, m), 4.61 (1H, c, J = 6.8 Hz), 3.02 (2H, t, J = 6.2 Hz), 2.71-2.82 (2H, m), 2.29 (3H, s), 1.48 (3H, d, J = 6.8 Hz), m / z = 321.

EXAMPLE 409 SYNTHESIS OF S-262 S-261 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methylthiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. NMR with lH at 400 MHz 8.16 (1H, d, J = 7.6 Hz), 7.83-7.88 (1H, m), 7.73 (1H, d, J = 8.4 Hz), 7.63 (1H, d, J = 7.2 Hz) , 7.44-7.51 (3H, m), 7.21 (2H, d, J = 8.0 Hz), 7.04-7.07 (2H, m), 4.59 (1H, c, J = 6.8 Hz), 2.85-2.96 (2H, m ), 2.61-2.74 (2H, m), 2.30 (3H, s), | l.79 (2H, tt, J = 7.1 Hz, J = 7.1 Hz), 1.47 (3H, d, J = 6.8 Hz), m / z = 335.

EXAMPLE 410 SYNTHESIS OF S-263 S-263 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-methylthiophenol, 1,5-dibromopentane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 424.

EXAMPLE 411 SYNTHESIS OF S-264 S-264 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 5-fluoro-2-mercaptobenzothiazole, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 438. EXAMPLE 412 S NTESIS OF S-265 110 mg (0.267 mmol) of K-2117 hydrochloride was dissolved in 2.2 ml of toluene (reagent grade). Then 56.0 mg (0.325 mmol) of m-chloroperbenzoic acid was added at room temperature, and the mixture obtained was stirred at the same temperature for 1 hour. After confirming that the reaction was complete, by TLC, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium thiosulfate was added at room temperature, and the reaction mixture was subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate. The obtained organic layer was further concentrated, under reduced pressure, and the residue was purified by column chromatography [silica gel, 5 g, chloroform / methanol = 150/1] to thereby give 82 mg (0.214 mmol, yield 78.3 %) of a pale yellow, syrup-like compound, S-265. m / z = 391.

EXAMPLE 413 SYNTHESIS OF S-266 500 mg (0.121 mmol) of K-2117 hydrochloride was dissolved in 20 ml of toluene (reagent grade). Then 58.0 mg (0.336 mmol) of m-chloroperbenzoic acid was added at room temperature, and the mixture obtained was stirred at the same temperature for 8 hours. After confirming that the reaction was complete, by TLC, a saturated aqueous solution of sodium bicarbonate and a saturated aqueous solution of sodium thiosulfate was added at room temperature, and the reaction mixture was subjected to stripping with chloroform and with a saturated aqueous solution of sodium chloride, and washed. The organic layer thus obtained was dried over anhydrous sodium sulfate. The obtained organic layer was further concentrated, under reduced pressure, and the residue was purified by column chromatography [silica gel, 5 g, chloroform / methanol = 150/1] to thereby give 28 mg (0.0686 mmol, yield 56.7 %) of a pale yellow compound, similar to syrup, S -166. m / z = 408.

EXAMPLE 414 SYNTHESIS OF F-8 g of 2,5-dichlorothiophenol was dissolved in 100 ml of acetonitrile. Then 7.8 g of N- (2-bromoethylphthalimide) was added while stirring at 0 ° C. Additional 4.04 g of potassium carbonate was added, after 1 hour water was added and the resulting mixture was extracted with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered and concentrated.The crystals thus obtained were washed with chloroform to thereby give 8.28 g of N- (2- (2 ', 5'-dichlorophenylthio) ethyl) phthalimide (F-8) MS m / z: 351 (M +).

EXAMPLE 415 SYNTHESIS OF F-37 7.06 g of N- (2- (2 ', 5'-dichlorophenylthio) -ethyl) phthalimide (F-8) was added to 120 ml of ethanol. After additionally 6.9 g of hydrazine monohydrate was added, the obtained mixture was heated to reflux for 1.5 hours. It was then brought to room temperature and water was added, after which it was extracted with chloroform. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered and concentrated. The crude product thus obtained was purified by column chromatography [silica gel, chloroform / methanol = 20: 1) to thereby give 4.29 g of 2- (2 ', 5'-dichlorophenylthio) ethylamine (F-37). MS m / z: 221 (M +).

EXAMPLE 416 SYNTHESIS OF F-12 250 mg of 2- (2 ', 5'-dichlorophenylthio) ethylamine (F-37) was mixed with 0.15 ml of 3'-methoxyacetophenone. After adding 0.4 ml of titanium tetraisopropoxide, the mixture was stirred for 3 hours. After adding 3 ml of ethanol, 43 mg of sodium borohydride was further added to the reaction mixture while cooling with ice. The mixture was then brought to room temperature and stirred for 15 hours. The reaction mixture was concentrated and ethyl acetate and water were added thereto. The insoluble material was filtered off and the organic layer was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered and concentrated. The crude product thus obtained was purified by means of column chromatography [silica gel, chloroform / methanol = 50: 1] to thereby give 146 mg of (±) -N- (1- (3-methoxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-12). MS m / z: 355 (M +).

EXAMPLE 417 SYNTHESIS OF F-12 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 ', 4'-dimethoxyacetophenone to give in that way (+) - N- (1- (3,4-dimethoxyphenyl) ethyl ) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-13).

MS m / z: 385 (M +).

EXAMPLE 418 SYNTHESIS OF F-14 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3'-methylacetophenone to thereby give (±) -N- (1- (3-methylphenyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-14). MS m / z: 339 (M +).

EXAMPLE 419 SYNTHESIS OF F-15 The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 4'-methylacetophenone to thereby give (±) -N- (1- (4-methylphenyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-13). MS m / z: 339 (M +).

EXAMPLE 420 SYNTHESIS OF F-16 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 ', 4', 5 '-trimethoxyacetophenone to give in that way (+) -N- (1- (3,4, 5-trimethoxy) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-16). MS m / z: 415 (M +).

EXAMPLE 421 SYNTHESIS OF F-17 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 4'-hydroxyacetophenone to thereby give (±) -N- (1- (4-hydroxyphenyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-17).

MS m / z: 341 (M +).

EXAMPLE 422 SYNTHESIS OF F-18 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3'- (trifluoromethyl) acetophenone to thereby give (±) -N- (1- (3-trifluoromethylphenyl) ethyl) - 2- (2 ', 5'-dichlorophenylthio) ethylamine (F-18). MS m / z: 393 (M +).

EXAMPLE 423 SYNTHESIS OF F-21 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 4'-hydroxy-3'-methoxyacetophenone to give in that way (+) -N- (1- (4-hydroxy-3 -methoxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-21). MS m / z: 371 (M +).

EXAMPLE 424 SYNTHESIS OF F-22 The procedure used for the synthesis of F-12 was repeated, but replacing the 3 * -methoxyacetophenone with 4'-bromoacetophenone to give in that way (±) -N- (1- (4-bromophenyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-22). MS m / z: 405 (M +).

EXAMPLE 425 SYNTHESIS OF F-23 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3'-bromoacetophenone to thereby give (+) - N- (1- (3-bromophenyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-23). MS m / z: 405 (M +).

EXAMPLE 426 SYNTHESIS OF F-24 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 2'- "bromoacetophenone to give in this way (+) -N- (1- (2-bromophenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-24) MS m / z: 405 (M +).

EXAMPLE 427 SYNTHESIS OF F-29 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 ', 4'-dihydroacetophenone to give in that way (±) -N- (1- (3, 4-dihydrophenylphenyl) ethyl ) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-29). MS m / z: 357 (M +).

EXAMPLE 428 SYNTHESIS OF F-30 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 2 ', 5'-dichloroacetophenone to thereby give (±) -N- (1- (2, 5-dichlorophenyl) ethyl ) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-30). MS m / z: 395 (M +).

EXAMPLE 429 SYNTHESIS OF F-31 The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 3'-fluoro-4'-methoxyacetophenone to give in that way (±) -N- (1- (3-fluoro-4) -methoxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-31). MS m / z: 373 (M +).

EXAMPLE 430 SYNTHESIS OF F-35 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 '- (trifluoromethoxy) acetophenone to thereby give (+) - N- (1- (3-trifluoromethoxyphenyl) ethyl) - 2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-35). MS m / z: 409 (M +).

EXAMPLE 431 SYNTHESIS OF F-48 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 ', 4'-dimethylacetophenone to thereby give (±) -N- (1- (3,4-dimethylphenyl) ethyl ) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-48). MS m / z: 353 (M +).

EXAMPLE 432 SYNTHESIS OF F-49 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 2'-chloroacetophenone to thereby give (±) -N- (1- (2-chlorophenyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) -ethylamine (F-49).

MS m / z: 359 (M +).

EXAMPLE 433 SYNTHESIS OF F-50 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3'-chloroacetophenone to give 'that way (±) -N- (1- (3-chlorophenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-50).

MS m / z: 359 (M +).

EXAMPLE 434 SYNTHESIS OF F-51 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 4'-chloroacetophenone to give in that way - (±) -N- (1- (4-chlorophenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-51).

MS m / z: 359 (M +).

EXAMPLE 435 SYNTHESIS OF F-52 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3'-fluoroacetophenone to thereby give (+) - N- (1- (3-fluorophenyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) -ethylamine (F-52).

MS m / z: 343 (M +).

EXAMPLE 436 SYNTHESIS OF F-53 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 41-fluoroacetophenone to thereby give (+) - N- (1- (4-fluorophenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-53).

MS m / z: 343 (M +).

EXAMPLE 437 SYNTHESIS OF F-54 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 2 ', 5'- dimethylacetophenone to thereby give (±) -N- (1- (2,5-dimethylphenyl) ethyl ) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-54).

MS m / z: 353 (M +).

EXAMPLE 438 SYNTHESIS OF F-55 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 2 ', 4'-' dimethylacetophenone to give in that way (±) -N- (1- (2,4-dimethylphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-55).

MS m / z: 353 (M +).

EXAMPLE 439 SYNTHESIS OF F-57 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 2 ', 4'-dichloroacetophenone to thereby give (+) - N- (1- (2, 4-dichlorophenyl) ethyl ) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-57).

MS m / z: 395 (M +).

EXAMPLE 440 SYNTHESIS OF F-58 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 ', 4'-dichloroacetophenone to thereby give (±) -N- (1- (3,4-dichlorophenyl) ethyl ) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-58).

MS m / z: 395 (M +).

EXAMPLE 441 S NTESIS OF F-63 200 mg of 3 '-hydroxyacetophenone was dissolved in 4 ml of acetonitrile. After adding 0.2 ml of ethyl iodide and 347 mg of potassium carbonate, the mixture was stirred for 9 hours at 70 ° C. After 9 hours, water and ethyl acetate were added to the reaction mixture, and then separated. The organic layer was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered and concentrated. The crude product thus obtained was purified by means of silica gel chromatography (n-hexane: ethyl acetate = 8: 1) to thereby give 204 mg of 3'-ethoxyacetophenone. The procedure used for the synthesis of F-12 was repeated, replacing 3'-methoxyacetophenone with 3'-ethoxyacetophenone to thereby give (±) -N- (1- (3-ethoxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-63).

MS m / z: 369 (M +).

EXAMPLE 442 SYNTHESIS OF F-64 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with n-propyl iodide, to thereby give 3'-n-propoxyacetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 '-n-propoxyacetophenone to give in that way (±) -N- (l- (3-n-propoxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-64). MS m / z: 383 (M +).

EXAMPLE 443 SYNTHESIS OF F-65 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with n-butyl iodide, to thereby give 3'-n-butoxyacetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 '-n-butoxyacetophenone to thereby give (+) - N- (1- (3-n-butoxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) -ethylamine (F-65). MS m / z: 397 (M +).

EXAMPLE 444 SYNTHESIS OF F-2255 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide by n-hexyl bromide, to thereby give 3'-n-hexyloxyacetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone by 3 '-n-hexyloxyacetophenone to thereby give (±) -N- (1- (3-n-hexyloxyphenyl) ethyl) -2- (21, 5'-dichlorophenylthio) -ethylamine (K-2255). MS m / z: 425 (M +).

EXAMPLE 445 SYNTHESIS OF F-67"The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing ethyl iodide with isopropyl iodide, to thereby give 3'-isopropoxyacetophenone. synthesis of F-12, but replacing 31-methoxyacetophenone by 3 '-isopropoxyacetophenone to give in that way (±) -N- (1- (3-isopropoxyphenyl) ethyl) -2- (2', 5'-dichlorophenylthio) ethylamine (F-67) MS m / z: 383 (M +).

EXAMPLE 446 SYNTHESIS OF F-68 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with dodecane iodide, to thereby give 3'-dodecyloxyacetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing 31-methoxyacetophenone with 3'-n-dodecyloxyacetophenone to give that way (±) -N- (1- (3-n-dodecyloxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-68). MS m / z: 509 (M +).

EXAMPLE 447 SYNTHESIS OF F-69 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing ethyl iodide AML with isobutyl iodide, to thereby give 3'-isobutoxyacetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 '-isobutoxyacetophenone to give in that way (±) -N- (1- (3-isobutoxyphenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-69). MS m / z: 697 (M +).

EXAMPLE 448 SYNTHESIS OF K-2258 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with 4-chlorobenzyl bromide, to thereby give 3 '- (4-chlorobenzyloxy) acetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 '- (4-chlorobenzyloxy) acetophenone to give in that way (+) -N- (1- (3- (4 - chlorobenzyloxy) phenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (K-2258). MS m / z: 465 (M +).

EXAMPLE 449 SYNTHESIS OF F-71 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with 3-chlorobenzyl bromide, to thereby give 3'- (2-chlorobenzyloxy) acetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing 31-methoxyacetophenone with 3 '- (2-chlorobenzyloxy) acetophenone to give in that way (±) -N- (1- (3- (2-chlorobenzyloxy) ) phenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-71). MS m / z: 465 (M +).

EXAMPLE 450 SYNTHESIS OF F-72 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with benzyl bromide, to thereby give 3'-benzyloxyacetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 3'-benzyloxyacetophenone to give in that way (±) -N- (1- (3-benzyloxyphenyl) ethyl) -2- ( 2 ', 5'-dichlorophenyl-thio) ethylamine (F-72). MS m / z: 431 (M +).

EXAMPLE 451 S NTESIS OF F-73 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with 2,6-dichlorobenzyl bromide, to thereby give 3 '- (2,6-dichlorobenzyloxy) acetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 3 '- (2,6-dichlorobenzyloxy) acetophenone to give in that way (±) -N- (1- (3- ( 2,6-dichlorobenzyloxy) phenyl) -ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-73). MS m / z: 501 (M +).

EXAMPLE 452 SYNTHESIS OF K-2260 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with l-bromo-6-chlorohexane, to thereby give 3 '- (6-chlorohexyloxy) acetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing 31-methoxyacetophenone with 3 '- (6-chlorohexyloxy) acetophenone to thereby give (±) -N- (1- (3 - (6-chlorohexyloxy) ) phenyl) ethyl) -2- (2 ', 5 • -dichlorophenylthio) ethylamine (K-2260). MS m / z: 459 (M +).

EXAMPLE 453 S NTESIS OF F-75 - The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing ethyl iodide with l-bromo-6-chlorohexane, to thereby give 3 '(2-chloroethoxy) acetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 '(2-chloroethoxy) acetophenone to give in that way (±) -N- (1- (3- (2-chloroethoxy ) phenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-75). MS m / z: 403 (M +).

EXAMPLE 454 SYNTHESIS OF F-76 The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with 2-methylbenzyl bromide, to thereby give 3'- (2-methylbenzyl) acetophenone. The procedure used for the synthesis of F-12 was repeated, but replacing 31-methoxyacetophenone with 3 '- (2-methylbenzyl) acetophenone to give in that way (+) - N - (1- (3- (2-methylbenzyl) ) phenyl) ethyl) -2- (2 •, 5'-dichlorophenylthio) ethylamine (F-76). MS m / z: 445 (M +).

EXAMPLE 455 S NTESIS OF K-2268 - The procedure used for the synthesis of 3'-ethoxyacetophenone was repeated, but replacing the ethyl iodide with 4-methylbenzyl bromide, to thereby give 3 '- (4-methylbenzyloxy) acetophenone . The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 3 '- (4-methylbenzyloxy) acetophenone to give in that way (±) -N- (1- (3- (4 - methylbenzyloxy) phenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (K-2268). MS m / z: 445 (M +).

EXAMPLE 456 SYNTHESIS OF F-78 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 2-acetyl-5-methylfuran, to give in that way (±) -N- (1- (2- (5-ethyl) ) furanyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-78).

MS m / z: 329 (M +).

EXAMPLE 457 SYNTHESIS OF F-79 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 2-acetylfuran, to thereby give (±) -N- (1- (2-furanyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-79). MS m / z: 315 (M +).

EXAMPLE 458 SYNTHESIS OF F-80 The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 2-acetyl-1-methylpyrrole, to thereby give (±) -N- (1- (2-1-methyl) pyrrolyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-80). MS m / z: 328 (M +).

EXAMPLE 459 SYNTHESIS OF F-81 • The procedure used for the synthesis of F-12 was repeated, but replacing the 3 '-methoxyacetophenone with 2-acetylthiophene, to give in that way (±) -N- (1- (2-thienyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-81). MS m / z: 331 (M +).

EXAMPLE 460 10 SYNTHESIS OF F-82 • The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 3-acetyl-2,5-dimethylfuran, to give in that way (±) -N- (1- (3-15) (2,5-dimethyl) furanyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-82). MS m / z: 343 (M +).

EXAMPLE 461 • SYNTHESIS OF F-83 20 The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 3-acetylthiophene, to give in that way (±) -N- (1- (3 -thienyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-83). MS m / z: 331 (M +).

EXAMPLE 462 SYNTHESIS OF F-84 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 2-acetyl-5-methylthiophene, to give in that way (±) -N- (1- (2- (5-methyl) ) thienyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-84).

MS m / z: 345 (M +).

EXAMPLE 463 SYNTHESIS OF F-85 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 3-acetyl-1-methylpyrrole, to give in that way (+) -N- (1- (3- (1-methyl) ) pyrrolyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-85).

MS m / z: 329 (M +).

EXAMPLE 464 SYNTHESIS OF F-86 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 5-acetyl-2,4-dimethylthiazole, to give in that way (±) -N- (1- (5- (2) , 4-dimethyl) thiazolyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-86). MS m / z: 360 (M +).

EXAMPLE 465 SYNTHESIS OF F-90 The procedure used for the synthesis of 3'-methoxyacetophenone but replacing the ethyl iodide with cyclohexylmethyl chromide was repeated to thereby give 3 '- (cyclohexylmethoxybenzyloxy) acetophenone. The procedure used for the synthesis of F-12 but replacing the 3'-methoxyacetophenone with the 3 '- (cyclohexylmethoxybenzyloxy) acetophenone was repeated to give that way (±) -N- (1- (3- (cyclohexylmethoxybenzyloxy) phenyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-90). MS m / z: 437 (M +).

EXAMPLE 466 - SYNTHESIS OF F-91 The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 2-acetylpyridine, to thereby give (±) -N- (1- (2-pyridyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-91). MS m / z: 327 (M +).

EXAMPLE 467 SYNTHESIS OF F-92 The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 3-acetylpyridine, to thereby give (±) -N- (1- (3-pyridyl) ethyl) -2- ( 2 ', 5'-dichlorophenylthio) ethylamine (F-92). MS m / z: 326 (M +). 5 EXAMPLE 468 SYNTHESIS OF F-93 The procedure used for the synthesis was repeated of F-12, but replacing 3 '-methoxyacetophenone by 4-? L? acetylpyridine, to thereby give (+) - N - (1- (4-pyridyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-93). MS m / z: 326 (M +).

EXAMPLE 469 SYNTHESIS OF F-94 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone by 2- 20 acetyl pyrazine, to thereby give (±) -N- (1- (2-pyrazyl) ethyl) -2- (2 ', 5'-dichlorophenylthio) ethylamine (F-94). MS m / z: 327 (M +).

EXAMPLE 470 SYNTHESIS OF F-95 The procedure used for the synthesis of F-12 was repeated, but replacing the 3'-methoxyacetophenone with 3-acetyl-2- (methylaminosulfonyl) thiophene, to give in that way (±) -N- (1- (3- ( 2-methylaminosulfonyl) thienyl) ethyl) -2- (2 *, 5'-dichlorophenylthio) ethylamine (F-95). MS m / z: 425 (M +).

EXAMPLE 471 SYNTHESIS OF F-96 The procedure used for the synthesis of F-12 was repeated, but replacing 3'-methoxyacetophenone with 3-acetylindole, to thereby give (±) -N- (1- (3-indolyl) ethyl) -2- ( 2 ', 5 • -dichlorophenylthio) ethylamine (F-96). MS m / z: 364 (M +).

EXAMPLE 472 SYNTHESIS OF F-97 450 mg of di (4-trifluoromethyl) benzylamine was dissolved in 10 ml of methylene chloride and 186 mg of bromoacetic acid was added thereto. After adding another 390 mg of SC. HCl, the reaction mixture was heated to reflux for 30 minutes. It was brought back to room temperature and separated to the aqueous and ethyl acetate layers. The organic layer was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The crude product thus obtained was purified by chromatography on silica gel (n-hexane: ethyl acetate = 3: 1) to thereby give 510 ppm of a bromine compound. 500 mg of this bromine compound was dissolved in 10 ml of acetonitrile and 763 mg of potassium carbonate and 0.18 ml of (R) - (+) - 1 - (1-naphthyl) ethylamine were added thereto. After adding another 41 mg of tetrabutylammonium iodide, the mixture was heated to reflux. After 2 hours it was brought back to room temperature and separated 4 to the aqueous and chloroform layers. The aqueous layer was washed with a saturated aqueous solution of sodium chloride, dried over sodium sulfate, filtered and concentrated. The crude product thus obtained was purified by column chromatography - of silica gel (n-hexane: ethyl acetate = 2: 1) to thereby give 280 mg of F-97 (MS m / z: 544 (M + l +). átk EXAMPLE 473 SYNTHESIS OF F-98 20 The procedure used for the synthesis of F-97 was repeated, but replacing the di (4-trifluoromethyl) benzylamine with (4-trifluoromethoxy) benzylamine, to thereby give F- 98. MS m / z: 576 (M + l +). 25 EXAMPLE 474 SYNTHESIS OF F-99 The procedure used for the synthesis of F-97 was repeated, but replacing the bromoacetic acid with 5-brompentanoic acid, to thereby give F-99. MS m / z: 586 (M +).

EXAMPLE 475 SYNTHESIS OF F-100 The procedure used for the procedure was repeated. synthesis of F-97, but replacing the di (4-trifluoromethyl) benzylamine with (4-chloro) benzylamine, to thereby give F-100. MS m / z: 476 (M +).

EXAMPLE 476 SYNTHESIS OF F-101 The procedure used for the synthesis of F-99 was repeated, but replacing the di (4-trifluoromethyl) benzylamine with di (4-trifluoromethoxy) benzylamine, to thereby give F-101. MS m / z: 618 (M +).

EXAMPLE 477 SYNTHESIS OF F-102 The procedure used for the synthesis of F-98 was repeated, but replacing the bromoacetic acid with 4-bromobutyric acid, to thereby give F-102. MS m / z: 604 (M +).

EXAMPLE 478 SYNTHESIS OF F-103 The procedure used for the synthesis of F-97 was repeated, but replacing the bromoacetic acid with 6-bromohexanoic acid, to thereby give F-103. MS m / z: 632 - (M +).

EXAMPLE 479 SYNTHESIS OF F-104 The procedure used for the synthesis of F-103 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine by di (4-trifluoromethyl) benzylamine, to thereby give F-104. MS m / z: 600 (M +) .

EXAMPLE 480 SYNTHESIS OF F-105 The procedure used for the synthesis of F-101 was repeated, but replacing the di (4-trifluoromethyl) benzylamine with di (4-chloro) benzylamine, to thereby give F-105. MS m / z: 533 (M + 1 +).

EXAMPLE 481 SYNTHESIS OF F-106 The procedure used for the synthesis of F-102 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine with di (4-chloro) benzylamine, to thereby give F-106. .MS m / z: 505 (M + l +).

EXAMPLE 482 SYNTHESIS OF F-107 The procedure used for the synthesis of F-99 was repeated, but replacing the di (4-trifluoromethyl) benzylamine with di (4-chloro) benzylamine, to thereby give F-107. MS m / z: 519 (M + 1 +).

EXAMPLE 483 SYNTHESIS OF F-108 The procedure used for the synthesis of F-98 was repeated, but replacing the bromoacetic acid with 8-bromooctanoic acid, to thereby give F-108. MS m / z: 660 (M +).

EXAMPLE 484 SYNTHESIS OF F-109 The procedure used for the synthesis of F-108 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine with di (4-trifluoromethyl) benzylamine, to thereby give F-109. MS m / z: 628 (M + l +).

EXAMPLE 485 SYNTHESIS OF F-110 The procedure used for the synthesis of F-108 was repeated, but replacing the di (4-trifluoromethyl) benzylamine with di (4-chloro) benzylamine, to thereby give F-110. MS m / z: 561 (M + l +).

EXAMPLE 486 SYNTHESIS OF F-lll The procedure used for the synthesis of F-99 was repeated, but replacing di (4-trifluoromethyl) benzylamine with di (4-trifluoromethylbenzyl) -N- (3,4-dichlorobenzyl) amine, to thereby give F-III . MS m / z: 587 (M + l +).

EXAMPLE 487 SYNTHESIS OF F-112 The procedure used for the synthesis of F-103 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine with di (4-trifluoromethylbenzyl) -N- (3,4-dichlorobenzyl) amine, to thereby give F-112 . MS m / z: 601 (M + l +).

EXAMPLE 488 SYNTHESIS OF F-113 The procedure used for the synthesis of F-97 was repeated, but replacing the di (4-trifluoromethyl) benzylamine by di (4-trifluoromethylbenzyl) -N- (3,4-dichlorobenzyl) amine, to thereby give F-113 . MS m / z: 544 (M +).

EXAMPLE 489 SYNTHESIS OF F-114 The procedure used for the synthesis of F-108 was repeated, but replacing di (4-trifluoromethoxy) benzylamine with di (4-trifluoromethylbenzyl) -N- (3,4-dichlorobenzyl) amine, to thereby give F-114 . MS m / z: 628 (M +).

EXAMPLE 490 SYNTHESIS OF F-115 The procedure used for the synthesis of F-102 was repeated, but replacing di (4-trifluoromethoxy) benzylamine with di (4-trifluoromethylbenzyl) -N- (3,4-dichlorobenzyl) amine, to thereby give F-115 . MS m / z: 572 (M +).

EXAMPLE 491 SYNTHESIS OF F-116 The procedure used for the synthesis of F-115 was repeated, but replacing 4-bromobutyric acid with 12-bromododecanoic acid, to thereby give F-116. MS m / z: 684 (M +).

EXAMPLE 492 SYNTHESIS OF F-117 The procedure used for the synthesis of F-102 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine with dibenzylamine, to thereby give F-117. MS m / z: 450 (M +).

EXAMPLE 493 SYNTHESIS OF F-118 The procedure used for the synthesis of F-103 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine with dibenzylamine, to thereby give F-118. MS m / z: 464 (M + l +).

EXAMPLE 494 SYNTHESIS OF F-119 The procedure used for the synthesis of F-108 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine with dibenzylamine, to thereby give F-119. MS m / z: 492 (M +).

EXAMPLE 495 SYNTHESIS OF F-120 The procedure used for the synthesis of F-97 was repeated, but replacing the di (4-trifluoromethoxy) benzylamine with dibenzylamine, to thereby give F-120. MS m / z: 408 (M +).

EXAMPLE 496 SYNTHESIS OF S-261 S-267 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol and (R) - (+) - 3-methoxy-O-benzylmethylamine, respectively, by 4- tert-butyl thiophenol and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 363.

EXAMPLE 497 SYNTHESIS OF S-268 S-268 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-tert-butylthiophenol, 1,3-dibromopropane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 377.

EXAMPLE 498 SYNTHESIS OF S-269 S-269 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-tert-butylthiophenol, 1,4-dibromobutane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 391.

EXAMPLE 499 SYNTHESIS OF S-270 S-270 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-tert-butylthiophenol, 1,5-dibromopentane and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 405.

EXAMPLE 500 SYNTHESIS OF S-271 S-271 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-tert-butylthiophenol, 1,6-dibromohexane and (R) - (+) - 1 - (1-naphthyl) ethylamine. m / z = 419.

EXAMPLE 501 SYNTHESIS OF S-272 S-272 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5-dimethylthiophenol, the l-bromo-2-chloroethane and the (R) - (+) - 3-methoxy- O-benzylmethylamine, respectively, by 4-tert-butylthiophenol, 1, 7-dibromoheptane and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 433.

EXAMPLE 502 SYNTHESIS OF S-273 S-273 was synthesized by almost the same method that was used for the synthesis of Sl, but replacing the 2,5- dimethylthiophenol, the 1-bromo-2-chloroethane and the (R) - (+) - 3-methoxy - O-benzylmethylamine, respectively, by 4-tert-butylthiophenol, 1,8-dibromooctane and (R) - (+) -1- (1-naphthyl) ethylamine. m / z = 447.

EXAMPLE 503 SYNTHESIS OF S-274 S-271 was synthesized by almost the same method that was used for the synthesis of S-265, but replacing K-2117 with K-2027. m / z = 399.

EXAMPLE 504 SYNTHESIS OF S-275 S-275 was synthesized by almost the same method that was used for the synthesis of S-265, but replacing K-2117 with K-2076. m / z = 433.

EXAMPLE 505 SYNTHESIS OF S-276 10 S-276 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- (trifluoromethoxy) benzaldehyde with 4-dimethylaminobenzaldehyde. fifteen - . 15 - EXAMPLE 506 SYNTHESIS OF S-277 jjL ^ S-277 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- 20 methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4-tert-butylbenzylamine and 3.4 - dichlorobenzaldehyde.

EXAMPLE 507 SYNTHESIS OF S-278 S-278 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-raethylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4-nitrobenzylamine and 3,4-dichlorobenzaldehyde.

EXAMPLE 508 SYNTHESIS OF S-279 S-279 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 3,4-dichlorobenzylamine and 4-dimethylaminobezaldehyde.

EXAMPLE 509 SYNTHESIS OF S-280 S-280 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- (trifluoromethoxy) benzaldehyde with 3,4-dimethoxybenzaldehyde.

EXAMPLE 510 SYNTHESIS OF S-281 S-281 was synthesized by almost the same method as was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, with 4- (trifluoromethyl) benzylamine and 3,4-dimethoxybenzaldehyde.

EXAMPLE 511 • SYNTHESIS OF S-282 S-282 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-15- (trifluoromethoxy) benzaldehyde with 3,4-dimethylbenzaldehyde.

EXAMPLE 512 SYNTHESIS OF S-283 • S-283 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4- (trifluoromethyl) benzylamine and 3,4- dimethylbenzaldehyde. 25 EXAMPLE 513 SYNTHESIS OF S-284 S-284 was synthesized by almost the same method that was used for the synthesis of K-2310, but 4- (trifluoromethoxy) benzaldehyde by and 3,4-dimethylenedioxybenzaldehyde.

EXAMPLE 514 SYNTHESIS OF S-285 S-285 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4-tert-butylbenzylamine and 4-tert-butylbenzaldehyde.

EXAMPLE 515 SYNTHESIS OF S-286 S-286 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- (trifluoromethoxy) benzaldehyde, respectively, by 4-chlorobenzaldehyde.

EXAMPLE 516 SYNTHESIS OF S-287 S-287 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4-chlorobenzylamine and 4-pyridinocarboxyalcehyde.

EXAMPLE 517 SYNTHESIS OF S-288 S-288 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- 'methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4- (trifluoromethyl) benzylamine and 4-pyridinocarboxylaldehyde.

EXAMPLE 518 SYNTHESIS OF S-289 S-289 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 3,4-dichlorobenzylamine and 4-phenylbenzaldehyde.

EXAMPLE 519 SYNTHESIS OF S-290 I S-290 was synthesized by almost the same method as was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 3,4-dimethylbenzylamine and 4-phenylbenzaldehyde.

EXAMPLE 520 SYNTHESIS OF S-291 S-291 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- 15-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 3,4-dimethoxybenzylamine and 4-phenylbenzaldehyde.

EXAMPLE 521 20 SYNTHESIS OF S-292 S-292 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 3,4-dichlorobenzylamine and 4-methylthiobenzaldehyde.

EXAMPLE 522 SYNTHESIS OF S-293 S-293 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 3,4-dimethylbenzylamine and 4-methylthiobenzaldehyde.

EXAMPLE 523 SYNTHESIS OF S-294 S-294 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 3,4-dimethoxybenzylamine and 4-methylthiobenzaldehyde.

EXAMPLE 524 SYNTHESIS OF S-295 S-295 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4- (trifluoromethyl) benzylamine and 3-chloro-4 -fluorobenzaldehyde.

EXAMPLE 525 SYNTHESIS OF S-296 S-296 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- (trifluoromethoxy) benzaldehyde with 3-chloro-4-fluorobenzaldehyde.

EXAMPLE 526 SYNTHESIS OF S-297 S-297 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4- (trifluoromethyl) benzylamine and 4-chloro-3 -nitrobenzaldehyde.

EXAMPLE 527 SYNTHESIS OF S-298 S-298 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4- (trifluoromethoxy) benzaldehyde with 4-chloro-3-nitrobenzaldehyde.

EXAMPLE 528 SYNTHESIS OF S-299 S-299 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4-chlorobenzylamine and 5-methyl-2-thiophenecarboxyaldehyde.

EXAMPLE 529 SYNTHESIS OF S-300 S-300 was synthesized by almost the same method that was used for the synthesis of K-2310, but replacing 4-methylbenzylamine and 4- (trifluoromethoxy) benzaldehyde, respectively, by 4- (trifluoromethyl) benzylamine and 5-methyl-2 -thiocarboxyaldehyde.

EXAMPLE 530 The activity of the compounds of the present invention on calcium receptors was measured. The measurement was carried out in accordance with the method described in example 4 of Nemeth and co-inventors, PCT / US95 / 13704 (international publication No. W096 / 12697). Briefly, HEK293 cells were transfected with a plasmid pHuPCaR4.0 containing a human calcium receptor gene, and loaded with fluo-3. Charging was carried out by incubating the cells at 37 ° C, in Dulbecco's modified Eagle's medium, containing about 5 μmoles of fluo-3 / AM, which had been regulated with 20 mmoles of HEPES. The cells were then rinsed with Hank's regulated salt solution containing 1 mmol of CaCl 2 and 1 mmol of MgCl 2, and which had been regulated with 20 mmoles of HEPES. Then each test compound was added to the cells and the fluorescence was measured with the use of an excitation wavelength of 485 nm and an emission wavelength of 540 nm. The results are shown in table 1.

TABLE 1 Compound E50 (μM) Compound E5Q (μM) 2 13 46 0.93 6 7.6 52 0.48 8 1.9 53 1.6 10 1.0 56 0.28 12 1.2 59 1.02 14 2.9 62 0.509 16 0.55 65 0.524 18 0.75 68 0.65 20 3.2 71 0.27 22 0.31 74 7.2 24 0.44 77 1.0 26 1.8 80 0.464 28 1.6 83 1.0 0.071 88 3.2 32 0.051 93 0.11 34 0.71 103 0.3 36 0.21 106 0.064 38 0.98 109 0.27 40 5.1 112 0.078 42 0.14 117 0.2 44 0.15 123 0.1 K-2003 0.29 K-2048 0.73 K-2004 0.42 K-2049 0.83 K-2005 0.43 K-2050 0.55 K-2006 0.77 K-2051 0.34 K-2007 0.47 K-2052 5.7 K-2008 0.86 K-2055 0.057 K-2010 0.14 K-2056 0.039 K-2011 0.21 K-2057 0.41 K-2012 0.87 K-2058 0.39 K-2015 0.49 K-2059 0.27 K-2016 0.36 K-2061 0.15 K-2017 0.36 K-2066 0.26 K-2018 0.33 K-2075 0.14 K-2027 0.39 K-2076 6.2 K-2030 0.049 K-2078 0.17 K-2033 0.35 K-2079 0.2 TABLE 1 (CONTINUED) Compound EC50 (μM) Compound EC50 (μM) K-2034 0.061 K-2080 0.77 K-2035 0.22 K-2082 2.81 K-2040 0.08 K-2084 0.12 K-2041 0.1 K-2085 0.13 K-2045 0.87 K-2087 0.087 K-2046 0.14 K-2117 0.043 K- 2047 0.13 K-2049 0.075 K-2240 0.36 K-2267 0.014 K-2243 0.092 K-2268 0.089 K-2246 0.12 K-2269 0.071 K-2247 0.13 K-2270 0.14 K-2248 0.078 K-2271 0.14 K-2249 0.082 K-2272 0.052 K-2250 0.076 K-2273 0.16 K-2251 0.051 K-2274 1.2 K-2252 0.018 K-2275 0.27 K-2253 0.19 K-2276 0.064 K-2254 0.088 K-2277 0.93 K-2255 9.6 K- 2278 2.50 K-2256 0.18 K-2279 0.63 K-2257 0.039 K-2280 0.27 K-2258 0.38 K-2281 0.43 K-2259 0.0024 K-2282 0.34 K-2260 0.096 K-2283 0.093 TABLE 1 (CONTINUED) Compound. E50 (μM) Compound EC50 (μM) K-2261 0.026 K-2284 0.36 K-2262 0.084 K-2285 0.32 K-2263 0.11 K-2286 0.62 K-2264 0.016 K-2287 0.062 K-2265 0.061 K-2288 0.14 K-2266 0.036 K-2289 0.074 K-2290 0.1 K-2306 1.85 K-2291 0.081 K-2309 0.066 K-2292 0.074 K-2310 0.059 K-2293 0.28 K-2311 0.053 K-2294 0.062 K-2312 0.08 K-2295 1.36 K-2314 0.29 K-2296 0.22 S-16 0.11 K-2297 0.23 S-52 0.16 K-2298 0.34 S-64 0.098 K-2299 • 0.15 S-69 0.31 K-2300 0.14 S-80 0.1 K-2301 0.8 S-165 0.15 K-2302 0.5 S-193 0.066 K-2303 0.35 S-201 0.18 K-2304 0.098 S-202 0.15 K-2305 0.11 S-265 0.91 EXAMPLE 531 The compound of the present invention was administered to rats in order to examine the effects of the compound on the level of calcium ion in the plasma and the level of HPT in the serum. The test was carried out by orally administering a single dose of the compound of the invention or of a control compound to normal SD male rats, with six animals in each group. Group 1, as control, was administered a 10% aqueous solution of cyclodextrin at a dose of 2.5 ml / kg. Group 2 was given, as reference, (R) -N- (3- (2-chlorophenyl) propyl) -1- (3-methoxyphenyl) ethylamine (KRN568) dissolved in a 10% aqueous solution of cyclodextrin, in a 30 μmole dose (kg) Group 3 was administered the compound of the present invention, dissolved in a 10% aqueous solution of cyclodextrin, at a dose of 30 μmoles / kg, with the restriction that aqueous solution was used as a % CMC sodium instead of 10% aqueous solution of cyclodextrin, for the compounds marked with ** in Table 2. Blood was collected from each rat at the tip of the tail, before administration and 30 minutes later, as well as at 1, 2, 4, 8 and 24 hours later (or the time indicated in Table 2), and the level of Ca2 + in the plasma and the level of HPT in the serum were measured. HPT level in the serum by means of multiple comparison analysis in accordance with the calibration of Steel, using group 1 as a The results are shown in Table 2 and Figures 46-96.

TABLE 2 Compound Ca in the plasma (mmol / liter) 0 hr 1 hr 2 hr 4 hr 8 hr 24 hr 48 hr K-2027 average 1,427 1,197 1,102 0.995 1,048 1,363 S.E. 0.010 0.063 0.027 0.027 0.024 0.013 K-2052 average 1.425 1.283 1.187 1.087 1.185 S.E. 0.015 0.012 0.117 0.016 0.006 K-2087 average 1.470 1.325 1.243 1.197 1.255 S.E. 0.008 0.015 0.009 0.012 0.008 K-2240 media 1,415 1,302 1,272 1,175 1,230 S.E. 0.009 0.038 0.022 0.027 0.003 K-2047 average 1.400 1.378 1.298 1.175 1.217 S.E. 0.016 0.014 0.018 0.018 0.016 K-2050 average 1.157 1.327 1.225 1.122 1.203 S.E. 0.014 0.030 0.022 0.010 0.019 K-2055 average 1.413 1.328 1.212 1.177 1.232 S.E. 0.020 0.013 0.019 0.009 0.012 K-2058 average 1.152 1.317 1.227 1.133 1.207 S.E. 0.009 0.015 0.026 0.031 0.014 K-2062 average 1.413 1.390 1.260 1.138 1.142 S.E. 0.020 0.009 0.021 0.017 0.020 K-2063 average 1.423 1.273 1.237 1.212 1.308 S.E. 0.11 0.028 0.024 0.016 0.011 K-2024 ** average 1.403 1.335 1.203 1.013 0.998 1.182 1.24? ' HE 0.015 0.019 0.019 0.019 0.021 0.027 0.017 K-2265 average 1,425 1,430 1,363 1,260 1,218 S.E. 0.019 0.012 0.010 0.022 0.008 K-2266 mean 1.417 1.368 1.222 1.065 1.045 1, .370 S.E. 0.020 0.021 0.036 0.023 0.017 0. .009 K-2267 mean 1.417 1.347 1.212 1.027 1.022 1, .312 S.E. 0.015 0.018 0.019 0.016 0.018 0, .023 K-2269 mean 1.450 1.152 1.140 1.097 1.173 S.E. 0.016 0.057 0.029 0.017 0.017 K-2270 ** average 1.430 1.355 1.238 1.088 1.175 S.E. 0.012 0.014 0.019 0.016 0.020 K-2271 average 1.428 1.278 1.227 1.128 1.197 S.E. 0.012 0.017 0.017 0.023 0.022 K-2272 ** mean 1.442 1.383 1.237 1.075 1.022 1, .240 S.E. 0.015 0.014 0.011 0.011 0.015 0, .012 K-2279 average 1.443 1.200 1.155 1.130 1.210 1. .445 S.E. 0.014 0.064 0.034 0.022 0.010 0, .015 K-2280 average 1.443 1.233 1.167 1.077 1.142 1, .405 S.E. 0.010 0.017 0.013 0.011 0.017 0, .008 K-2281 average 1.437 1.380 1.245 1.103 0.993 1. .230 * b S.E. 0.015 0.017 0.031 0.011 0.011 0, .014 K-2282 ** average 1.435 1.425 1.298 1.168 1.078 1, .230 * b S.E. 0.016 0.019 0.015 0.017 0.010 0. .014 K-2283 ** average 1.433 1.395 1.305 1.210 1.253 S.E. 0.016 0.015 0.014 0.013 0.014 TABLE 2 (CONTINUED) Compound Ca2 + in plasma (mmol / liter) 0 hr 1 hr 2 hr 4 hr 8 hr 24 hr 48 hr K-2284 average 1,428 1,377 1,267 1,152 1,102 S.E. 0.018 0.011 0.025 0.025 0.020 K-2286 average 1.405 1.318 1.218 1.088 1.098 1, .390 1.412 HE 0.017 0.015 0.018 0.021 0.018 0. .008 0.014 K-2287 average 1,403 1,180 1,042 0.955 0.950 1. .200 1,392 HE 0.013 0.019 0.017 0.019 0.006 0. .041 0.012 K-2288 average 1.405 1.190 1.057 0.955 0.950 1. .162 1.387 HE 0.012 0.018 0.020 0.018 0.009 0. .020 0.015 K-2289 ** average 1,407 1,270 1,173 1,003 1,093 S.E. 0.013 0.018 0.022 0.017 0.025 K-2290 ** average 1.380 1.428 1.248 1.063 1.055 S.E. 0.007 0.014 0.028 0.019 0.033 K-2291 ** average 1.410 1.298 1.247 1.130 1.132 S.E. 0.017 0.041 0.022 0.021 0.019 K-2292 average 1.412 1.375 1.252 1.152 1.108 S.E. 0.014 0.007 0.012 0.015 0.015 K-2293 average 1.408 1.245 1.152 1.068 1.088 S.E. 0.012 0.039 0.022 0.020 0.014 K-2294 ** average 1.410 1.357 1.255 1.117 1.022 S.?. 0.018 0.014 0.022 0.026 0.015 K-2296 ** average 1.410 1.340 1.195 1.113 1.083 S.E. 0.013 0.009 0.013 0.014 0.016 K-2297 ** average 1.405 1.393 1.305 1.172 1.082 S.E. 0.016 0.010 0.022 0.016 0.022 TABLE 2 (CONTINUED) Compound Ca + in plasma (mmol / liter) 0 hr 1 hr 2 hr 4 hr 8 hr 24 hr 48 hr K-2298 average 1 .405 1 .348 1, .265 1,187 1,100 S.E. 0 .015 0 .015 0, .030 0.024 0.017 K-2299 average 1. .395 1, .287 1, .192 0.998 0.983 1 .382 * c S.E. 0 .015 0. .013 0, .021 0.019 0.014 0 .013 K-2300 - ** average 1, .395 1, .293 1, .158 0.958 1.022 1 .397 * c S.E. 0, .014 0, .015 0. .019 0.022 0.014 1 3.020 K-2301 average 1 .397 1, .237 1, .165 1,077 1,075 1,350 * S.E. 0 .009 0 .030 0, .017 0.024 0.019 1 3.010 K-2302- * average 1. .412 1. .238 1. .130 0.978 1.010 S.E. 0, .014 0, .019 0. .013 0.016 0.016 K-2303 average 1, .415 1. .255 1. .165 1.020 1.032 S.E. 0. .018 0. .021 0. .018 0.010 0.023 K-2304 average 1. .382 1. .262 1. .157 1.053 1.065 S.E. 0. .014 0. .029 0. .023 0.006 0.012 K-2305 average 1. .415 1. .242 1. .170 1,098 1.202 S.E. 0. .015 0. .018 0. .013 0.025 0.022 K-2309 average 1. .428 1. .320 1. .207 1.018 0.963 1 .332, ** dd S.E. 0. .016 0. .012 0. .024 0.029 0.008 0 .003 K-2310 average 1. .428 1. .342 1. .188 1.1008 0.943 1 .330, ** dd S.E. 0. .014 0. .014 0. .025 0.026 0.013 0 .014 K-2311 '* - * average 1. .447 1. .375 1. .232 1.075 1.110 S.E. 0. .014 0. .011 0. .012 0.016 0.034 KRN568 average 1. .378 1. .305 1. .237 1,290 1,340 S.E. 0. .018 0. .014 0. .08 0.012 0.015 NOTE: * a: 31 hrs;; * b: 27 hr; * c: 23 hr; * d: 28 hr As the tables and figures clearly show, the compound of the present invention is capable of decreasing the level of Ca in the plasma and the level of HPT in the serum, in vivo.

Claims (6)

1. NOVELTY OF THE INVENTION CLAIMS 1. - A compound characterized in that it has the formula: Arx- [CRl-R2] pX- [CR3R4] q [CR5R6] -NR7- [CR8R9] -Ar2 wherein: Ar ^ is selected from the group consisting of aryl, heteroaryl, bis (arylmethyl) amino, bis (heteroarylmethyl) -amino and arylmethyl (heteroarylmethyl) amino; X is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl and amino; R1, R2, R3, R4, R5, R6, R8 and R9 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, trihalogenomethyl, aryl, heteroaryl, heteroalicyclic, halogen, hydroxy, alkoxy, thioalkoxy, aryloxy , thioaryloxy, carbonyl, thiocarbonyl, C-carboxyl, O-carboxyl, C-amido, N-amido, O-carbamyl, N-carbamyl, O-thiocarbamyl, N-thiocarbamyl, cyano, nitro, amino and NR R; wherein: R and R are independently selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, carbonyl, trihalogenoacetyl, sulfonyl, trihalogenomethanesulfonyl and, in combination, a five or six membered heteroalicyclic ring containing at least a nitrogen; any two adjacent "R" groups can be combined to form five or six membered fused cycloalkyl groups; R is selected from the group consisting of hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, halogen, cyano, hydroxy, alkoxy, 0-carbonyl, trihalogenoacetyl and trihalogenomethanesulfonyl; Ar2 is selected from the group consisting of aryl and heteroaryl; p is an integer from 0 to 6, inclusive; and q is an integer 'from 0 to 14, inclusive; or a pharmaceutically acceptable salt or hydrate of said compound.
2. 2. The compound, salt or hydrate according to claim 1, further characterized in that R5 is selected from the group consisting of hydrogen, unsubstituted lower alkyl and lower alkyl substituted with one or more halogens; and R and R are hydrogen.
3. 3. The compound, salt or hydrate, according to claim 2, further characterized in that R5 is hydrogen.
4. 4. The compound, salt or hydrate, according to claim 3, further characterized in that R, R2, R and R are hydrogen.
5. 5. The compound, salt or hydrate according to claim 4, further characterized in that R 8 and n-n are independently selected from the group consisting of hydrogen, unsubstituted alkyl, lower alkyl substituted with one or more halogens , unsubstituted alkenyl, lower alkenyl substituted with one or more halogens, unsubstituted alkynyl, alkynyl substituted with one or more halogens, and unsubstituted cycloalkyl and cycloalkenyl, combined.
6. 6. The compound, salt or hydrate according to claim 5, further characterized in that Ar] _ is selected from the group consisting of phenyl, naphthyl, indolyl, fluorenyl, dibenzofuranyl, carbazolyl, benzoxazol-2-yl, benzothiazol-2-yl, pyridin-4-yl, quinolin-2-yl and dibenzylamino. 1 . - The compound, the salt or the hydrate, according to claim 6, further characterized in that Ar ^ is optionally substituted with one or more groups independently selected from the group consisting of halogen, unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, hydroxy, unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, nitro, unsubstituted phenyl and phenyl substituted with one or more groups selected from unsubstituted lower alkyl, halogen, trihalogenomethyl and trihalogenomethoxy; R is hydrogen and R is unsubstituted lower alkyl. 8. The compound, salt or hydrate according to claim 7, further characterized in that Ar is selected from the group consisting of phenyl, naphthyl, quinolin-4-yl, pyridin-2-yl, pyridin-3. ilo, pyridin-4-yl, pyrimidinyl, furan-2-yl, furan-3-yl, thiophen-2-yl, thiophen-3-yl, pyrrol-2-yl and pyrrol-3-yl. 9. - The compound, the salt or the hydrate, according to claim 8, further characterized in that Ar2 is optionally substituted with one or more groups independently selected from the group consisting of unsubstituted middle alkyl, middle alkyl substituted with one or 5 more halogens , hydroxy, unsubstituted middle alkoxy, lower alkoxy substituted with one or more halogens, halogen, unsubstituted benzyloxy, benzyloxy substituted with one or more groups independently selected from halogen and methyl. 10. The compound, salt or hydrate, according to claim 6 or 7, further characterized • because Ar2 is selected from the group consisting of optionally substituted phenyl and optionally substituted naphthyl. 11. The compound, salt or hydrate, according to claim 9 or 10, further characterized Because Ar_ is phenyl substituted with one or more groups selected from the group consisting of unsubstituted lower alkyl, halogen, trihalogenomethyl, unsubstituted lower alkoxy, trihalogenomethoxy, trihalogenoacetyl and nitro. 12. The compound, salt or hydrate according to claim 11 further characterized in that p is 1 and Ar2 is selected from the group consisting of 3-methoxyphenyl and unsubstituted naphthyl. 13. The compound, salt or hydrate, according to claim 12, further characterized in that q is an integer from 1 to 8, inclusive. 14. The compound, salt or hydrate according to claim 11 further characterized in that p is 0, Ar is 3-methoxyphenyl or unsubstituted naphthyl and q is an integer from 1 to 8, inclusive. 15. The compound, salt or hydrate according to claim 14, further characterized in that Rg is hydrogen and Rg is methyl. 16. The compound, salt or hydrate, according to claim 15, further characterized in that X is selected from the group consisting of oxygen and sulfur. 17. The compound, salt or hydrate according to claim 16, further characterized in that the compound is the R-enantiomer. 18. A prodrug of any of the compounds of claims 1 to 17, inclusive. 19. A compound of the formula: Ar3- (CHR12) rQ- (CH2) S-CHR13 -NH-CR14R15-Ar4 wherein: Ar3 is selected from the group consisting of aryl and heteroaryl, optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkenyl, lower alkenyl substituted with one or more halogens, halogen, hydroxy, unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, unsubstituted lower thioalkoxy, nitro, formyl, acetoxy, acetyl, -CH 0H, 411 CH 3 CH (OH) -, -C (= 0) NH 2, cyano, -N (lower alkyl) 2, phenyl, phenoxy, benzyl, benzyloxy, methylenedioxy, ethylenedioxy, O, O-dimethylbenzyl and -0CH 2 C00H; Ar4 is selected from the group consisting of aryl and heteroaryl optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkenyl, substituted lower alkenyl, one or more halogens, unsubstituted lower alkoxy, lower alkoxy 10 substituted with one or more halogens, hydroxy, thioalkoxy »Lower, halogen, methylenedioxy, ethylendioxy, acetoxy, -0CH C00H, -C (= 0) NH2, cyano and -CH2OH; r is an integer from 0 to 6, inclusive; s is an integer from 0 to 14, inclusive; Q is selected from the group consisting of oxygen, sulfur, Carbonyl and -NH-; R is hydrogen or lower alkyl; and R14 and R are independently selected from the group consisting of hydrogen, alkyl and, in combination, cycloalkyl and cycloalkenyl; or a pharmaceutically acceptable salt of a hydrate of said compound. 20. The compound, the salt, the hydrate or the prodrug according to claim 19, further characterized in that: Ar is selected from the groups consisting of unsubstituted phenyl, phenyl substituted with one or more groups selected from the group consists of lower alkyl no Substituted, lower alkyl substituted with one or more halogens, halogen, unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, nitro, dimethylamino and unsubstituted phenyl, and optionally substituted naphthyl; Ar4 is selected from the groups consisting of unsubstituted phenyl, phenyl substituted with one or more groups selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens and halogen, and optionally substituted naphthyl; R is selected from the group consisting of unsubstituted lower alkyl and lower alkyl substituted with one or more halogens; and R 5 is hydrogen. 21. The compound, the salt, the hydrate or the prodrug according to claim 20, further characterized in that: Ar3 is selected from the group consisting of unsubstituted phenyl, phenyl substituted with one or more groups selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, halogen, unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, nitro, dimethylamino and unsubstituted phenyl, and unsubstituted naphthyl; Ar is selected from the group consisting of unsubstituted phenyl, phenyl substituted with one or more groups selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkoxy, lower alkoxy substituted with one or more more halogens and halogen, and unsubstituted naphthyl; r is 0 or 1, where, when r is 1, R "1 is hydrogen 22. The compound, salt or hydrate according to claim 21, further characterized in that s is an integer from 1 to 8, inclusive 23. The compound, salt or hydrate according to claim 21, further characterized in that s is an integer from 1 to 5, inclusive 24. The compound, salt or hydrate according to claim 23 also characterized in that Q is selected from the group consisting of oxygen and sulfur 25. The compound, salt or hydrate according to claim 23, further characterized in that R is selected from the group consisting of hydrogen and methyl. The compound, salt or hydrate according to claim 25, further characterized in that R is hydrogen and R 14 is methyl 27. The compound, salt or hydrate according to claim 26, further characterized in that compound is the R. 2 enantiomer 8. A prodrug of any of the compounds of claims 19 to 27, inclusive. 29. A compound of the formula: Ar5- (CHR16) t- - (CH2) U-CHR17-NH-CH (R18) -Ar6 in which: Ar5 is aryl, dicyclic or tricyclic heteroaryl, arylmethyl (arylmethyl) amino , eteroarylmethyl (heteroarylmethyl) amino or arylmethyl (heteroarylmethyl) amino, optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, unsubstituted lower alkenyl, halogen, hydroxy, unsubstituted lower alkoxy, unsubstituted lower thioalkoxy , lower alkyl substituted with one or more halogens, lower alkenyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, formyl, acetoxy, acetyl, -CH20H, CH3CH (OH) -, -C (= 0 ) NH 2, cyano, N (unsubstituted lower alkyl) 2 / phenyl, phenoxy, benzyl, benzyloxy, O, O-dimethylbenzyl, methylenedioxy, ethylenedioxy and -OCH 2 COOH; Arg is aryl, or dicyclic or tricyclic heteroaryl optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, lower alkyl substituted with one or more halogens, unsubstituted lower alkenyl, lower alkenyl substituted with one or more halogens , unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens, halogen, hydroxy, unsubstituted lower trialkoxy, lower trialkoxy substituted with one or more halogens, benzyloxy, methylenedioxy, ethylenedioxy, acetoxy, -COH2COOH, -C (= 0) NH2, cyano and -CH2OH; t is 0 or 1; u is an integer from 0 to 11, inclusive; W is selected from the group consisting of oxygen, sulfur, sulfinyl, sulfonyl, carbonyl and amino; R16 and R17 are H or unsubstituted lower alkyl; and R18 is unsubstituted lower alkyl; or a pharmaceutically acceptable salt or hydrate of said compound. 30. The compound, salt or hydrate according to claim 29, further characterized in that Ar5 is phenyl, indole, benzothiazole, benzoxazole, dibenzofuran, carbazole, pyridine, fluorene, quinoline, naphthalene, chromenone, tetrahydrobenzothiazepine, dibenzylamino, benzyl (naphthylmethyl) ) -amino, benzyl (pyridylmethyl) amino, thienylmethyl (benzyl) amino, furylmethyl (benzyl) amino or N-alkyl-pyrrolylmethyl (benzyl) amino optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens, lower alkoxy substituted with one or more halogens, nitro, dimethylamino and unsubstituted phenyl; and Arg is thiophene, furan, pyrrole, phenyl, naphthalene, pyridine, pyrazine or thiazole optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more more halogens, lower alkoxy substituted with one or more halogens, hydroxy and benzyloxy optionally substituted with halogen or methyl; R16 and R17 are H or methyl; and R18 is methyl. 31. The compound, salt or hydrate according to claim 30, further characterized in that Ar5 is phenyl, benzothiazole, benzoxazole, dibenzofuran, carbazole, pyridine, quinoline or naphthalene optionally substituted with one or more groups independently selected from the group consists of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens and lower alkoxy substituted with one or more halogens; Arg is phenyl or naphthalene, wherein the phenyl is optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkoxy, lower alkoxy substituted with one or more halogens and benzyloxy optionally substituted with halogen or methyl; t is 0; u is an integer from 1 to 8, inclusive; it is sulfur; and R 7 is H. The compound, salt or hydrate according to claim 31, further characterized in that Ar 5 is selected from the group consisting of phenyl optionally substituted with one or more groups independently selected from the group consisting of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens and lower alkoxy substituted with one or more halogens; Arg is 3-methoxyphenyl or O-naphthyl, and u is an integer from 2 to 6, inclusive. 33. The compound, salt or hydrate according to claim 30, further characterized in that Ar5 is dibenzylamino, benzyl (naphthylmethyl) amino or benzyl (pyridylmethyl) -amino, optionally substituted with one or more groups independently selected from the group consists of unsubstituted lower alkyl, halogen, unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens and lower alkoxy substituted with one or more halogens; Arg is naphthyl or methoxyphenyl; t is zero; u is an integer from 0 to 8, inclusive; it is carbonyl; and R 17 is H. 34.- The compound, salt or hydrate according to claim 33, further characterized in that Ar 5 is dibenzylamino optionally substituted with one or more groups independently selected from the group consisting of unsubstituted alkyl, halogen , unsubstituted lower alkoxy, lower alkyl substituted with one or more halogens and lower alkoxy substituted with one or more halogens; Arg is 3-10-methoxyphenyl or O-naphthyl; yu is 1. ^ 35.- The compound, salt or hydrate according to any of claims 29 to 34, further characterized in that the compound is the R. 36. - (R) -N- [1- ( 1'-naphthyl) ethyl] -2- (2 ', 5'-dichlorophenyl-15 thio) ethylamine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (5- { [ 4- (trifluoromethoxy) phenyl] thio.) Pentyl) amine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (4 { [4- (trifluoromethoxy) phenyl] thio} butyl) amine, N-. { 4- [(2,4-] dimethylphenyl) thio] butyl} -N- [(IR) -1- (1-naphthyl) ethyl] amine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (5- { [4- (trifluoromethyl) phenyl] thio.) - pentiDamine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (4- {[2, 4, 5- (trichlorophenyl) thio] butyl}. amine, N- { 5- [(4-chlorophenyl) thio] -pentyl.}. -N- [(IR) -1- (1-naphthyl) ethyl] amine, N-. {5- [ (2,4-dimethylphenyl) thio] pentyl.} - N - [(IR) -1- (1-naphthyl) ethyl] amine, N - [(IR) -1- (1-naphthyl) ethyl] -N - (4- { [4- (trifluoromethyl) phenyl] thio.} Butyl) amine, 25 N-. { 4- [(4-methylphenyl) thio] butyl} -N- [(IR) -1- (1-naphthyl) ethyl] amine, N-. { 4- [(4-chlorophenyl) thio] butyl} -N- [(IR) -1- (1-naphthyl) ethyl] amine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (6- { [4-trifluoromethoxy) phenyl ] -uncle} hexyl) amine, N-. { 5- [(4-methoxyphenyl) thio] pentyl} -N- [(IR) -1- yl-naphthyl) ethyl] amine, N- [(IR) -1- (l-naphthyl) ethyl] -N- (5- { [2,4,5- (trichlorophenyl) thio] pentyl} amine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (4- { [2,3,5,6-tetrafluoro-4- ( trifluoromethyl) phenyl] thio.) - butyl) amine, N-. {5 - [(2,5-dichlorophenyl) thio] pentyl} -. N - [(IR) -1- (1-naphthyl) ethyl] ] amine, N- { 5- [(4-fluorophenyl) thio] pentyl}. -N- [(IR) -1- (1-naphthyl) ethyl] amine, N- { 6- [( 4-chlorophenyl) thio] hexyl.}. -N- [(IR) -1- (1-naphthyl) ethyl] amine, N- { 4- [(3-methoxyphenyl) thio] butyl}. - [(IR) -1- (1-naphthyl) ethyl] amine, N- { 5- [(4-methylphenyl) thio] pentyl}. -N- [(IR) -1- (1-naphthyl) ) ethyl] amine, N- { 4- [(2,5-dichlorophenyl) thio] -butyl}. -N- [(IR) -1- (1-naphthyl) ethyl] amine, N- [( IR) -1- (1-naphthyl) -ethyl] -N- (5- {[[2,3,5,6-tetrafluoro-4- (trifluoromethyl) phenyl] thio}. -pentyl) amine, N - [(IR) -1- (1-naphthyl) ethyl] -N- (7- { [2,3,5,6-tetrafluoro-4- (trifluoromethyl) phenyl] thio.} Heptyl) amine, N- { [4- ( 5-ethoxy-l, 3-benzothiazol-2-yl) thio] butyl] -N- [(IR) -1- (1-naphthyl) -ethyl] amine, N-. { [5- (3-methoxyphenyl) thio] pentyl] -N- [(IR) -1- (1-naphthyl) ethyl] amine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (3- { [4- (trifluoromethyl) phenyl] thio.] Propyl) amine, N- [(IR) -1- (1-naphthyl) ethyl] -N- (4- { [3- (trifluoromethyl) phenyl] thiojbutyl) amine, N-. { [4- (4-fluorophenyl) thio] butyl] -N- [(IR) -1- (1-naphthyl) ethyl] amine, N 1 - (4-methylbenzyl) -N 1 - [4- (trifluoromethoxy) benzyl] - 3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N1, N '-di (4-methylbenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N '- (3,4-dichloro-benzyl) -N' - (4-methoxybenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} -propanamide, N 1 - (4-methylbenzyl) -N '[4- (trifluoromethyl) benzyl] -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N 1 - (3,4-dichloro-benzyl) -N '[4- (trifluoromethyl) benzyl] -3-. { [(IR) -1- (1-naphthyl) -ethyl] amino} propanamide, N '- (4-chlorobenzyl) -N' (4-methoxybenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N '- (4-chlorobenzyl) -N' (3,4-dichlorobenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] -amino} propanamide, N '- (3,4-dichlorobenzyl) -N' [4- (trifluoromethoxy) benzyl] -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N '- (3,4-dichlorobenzyl) -N'- (4-methylbenzyl) -3-. { [(IR) -1- (1-naphthyl) -ethyl] amino} propanamide, N ', N' -di [4- (trifluoromethoxy) benzyl] -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N 1 - (4-chlorobenzyl) -N 1 [4- (trifluoromethyl) benzyl] -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} -propanamide, N '- (4-methoxybenzyl) -N' [4- (trifluoromethyl) benzyl] -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N ', N' -di [4- (trifluoromethoxy) benzyl] -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} -propanamide, N ', N' -di (4-chlorobenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N1, N '-di (4-methoxybenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N '-benzyl-N' - (3,4-dichlorobenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N '- (4-chlorobenzyl) -N' - (2-naphthylmethyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] -amino} propanamide, N '- (2-chlorobenzyl) -N' - (4-chlorobenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N '-benzyl-N' - (4-chlorobenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, N '- (4-chlorobenzyl) -N' - [4- (trifluoromethoxy) benzyl] -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, or N1, N '-di (3,4-dichlorobenzyl) -3-. { [(IR) -1- (1-naphthyl) ethyl] amino} propanamide, or a salt or hydrate thereof. 37. - A pharmaceutical composition characterized in that it comprises the compound, the salt or the hydrate of any of claims 1 to 36, inclusive. 38.- A method for treating a patient, characterized in that it comprises administering to the patient a therapeutically effective amount of one or more of the compounds of claims 1 to 37. 39.- The method according to the claim 38, further characterized in that the patient suffers from a disease or disorder characterized by either or both: (1) abnormal calcium homeostasis; or (2) an abnormal amount of an intracellular or extracellular messenger whose production may be affected by the activity of the calcium receptor. 40.- A method for modulating the level of HPT in a patient, characterized in that it comprises administering to the patient an effective amount of the compound of claims 1 to 37. 41.- The method according to the claim 40, further characterized in that the effective amount of the compound of claims 1 to 37 reduces the level of HPT in a patient. 42. - The method of compliance with the claim 41, further characterized in that the patient has an abnormally high level of HPT and the effective amount of a compound of claims 1 to 37 reduces said level of HPT in the patient to a sufficient degree to cause a decrease in plasma Ca. 43. A method for reducing the level of HPT in a patient to a level present in a normal individual, characterized in that it comprises administering to the patient a The effective amount of a compound of claims 1 to 37. 44. A method for modulating the secretion of parathyroid hormone in a patient, characterized in that it comprises administering to the patient an effective amount of the compound of 10 claims 1 to 37. • 45.- The method according to the claim 44, further characterized in that the effective amount of the compound of claims 1 to 37 reduces the secretion of parathyroid hormones in the patient. 15 46.- The method of compliance with the claim 45, further characterized in that the patient has an abnormally high secretion in the parathyroid, and the amount Therapeutically effective W of the compound of the claims 1 to 37 reduces the secretion of parathyroid hormone in the patient to an amount sufficient to cause a decrease in Ca + in the plasma. 47. A method for modulating one or more activities of Ca2 + receptors in a cell, characterized in that it comprises administering one or more of said compounds, salts or hydrates of claims 1 to 37, to said cell. 48. The method according to claim 47, further characterized in that the cell is a parathyroid cell, a juxtaglomerular kidney cell, a kidney cell of the proximal tubule, a parafollicular thyroid cell, a bone osteoclast, a keratinocyte or a placental trophoblast. 49. A method for treating or preventing a disorder selected from the group consisting of hyperparathyroidism, renal osteodystrophy, hypercalcemic malignancy, osteoporosis of Paget and hypertension, characterized in that it comprises administering to a patient suffering from said disorders a therapeutically effective amount of the Compounds of claims 1 to 37. 50. The method according to claim 49, further characterized in that the hyperparathyroidism is primary hyperparathyroidism. 51. The method according to claim 49, further characterized in that the hyperparathyroidism is secondary hyperparathyroidism. 52. - A pharmaceutical composition for treating primary and secondary hyperparathyroidism, characterized in that it comprises the compound, salt or hydrate of any of claims 29 to 36. 53. - A pharmaceutical composition for treating renal osteodystrophy, characterized in that it comprises the compound, the salt or the hydrate of any of claims 29 to 36. 54. - A pharmaceutical composition for treating hypercalcemia, characterized in that it comprises the compound, salt or hydrate of any of claims 29 to 36. - A pharmaceutical composition for treating malignant hypercalcemia, characterized in that it comprises the compound, the salt or the hydrate. of any of claims 29 to 36. 56.- A pharmaceutical composition for treating osteoporosis, characterized in that it comprises the compound, salt or hydrate of any of claims 29 to 36.