MXPA99005532A - Indane or dihydroindole derivatives - Google Patents

Abstract

The present invention relates to substituted indane or dihydroindole compounds of Formula (I) wherein A is an indole. These compounds have high affinity for D4 receptors.

Description

INDIAN OR DIHYDROINDOL DERIVATIVES Field of the Invention The present invention relates to a novel class of substituted indane or dihydroindol compounds with effects on dopamine D4 receptors. The compounds are selective dopamine D4 ligations, or have had combined effects on dopamine D4 receptors and 5-HT and / or 5-HT transporter. These compounds are, therefore, useful in the treatment of certain neurological and psychiatric disorders, including psychosis, depression and anxiety.

Background of the Invention Related compounds are known from ED 44 14 113 A1 by describing certain piperidines of 4- (indol-3-i 1) -1- (indol-3-yl-1-alkylene). The compounds are claimed to show the antagonistic and agonistic activities and to have effects on the accumulation of DOPA in striatum. No biological data are provided. Great Britain Patent Application No. 2 044 254 discloses certain derivatives of 1- (indol-3-yl-alkylene) -piperidine, which are substituted in the 3 or 4 position of the piperidine with an isoindol, or a ring of isoquinoline. The compounds are claimed to have a 5-HT reabsorption activity and to be useful as antidepressants. Furthermore, in WO Patent No. WO 9421627, No. WO 9421630 and No. WO 9421626, several series of derivatives of indolyl- or indazole i lme t i 1 piperidine or piperazine are described, to be selective dopamine D4 antagonists. No data is given. The compounds only give Kx values of less than 1.5 μM in a test for the displacement of 3 H spiperone from human D4 dopamine receptor subtypes in clonal cell lines. WO patent No. 95/33721 relates to piperidine, t-t-rahydropyridine, or piperazine of 1- (indamethyl, dihydrobenzofuranyl, or dihydrobenzot iofenylmethyl). The 1-indamethyl compounds disclosed in the present invention are substituted in the 6-position with a nitrogen-containing group. The compounds interact with central 5-HT receptors, in particular, with 5-HT1A and 5-HT2A receptors. Some of the compounds have a 5-HT reuptake inhibitory effect.

Dopamine D4 receptors belong to the family of dopamine D2 receptors considered responsible for the antipsychotic effects of neuroleptics. In addition, dopamine D4 receptors are mainly located in areas of the brain other than s tri atum (Van Tol, et al., Nature (Nature), 1991, 350, 610), the low level in striatum that suggests lack of external activity. rapiramidal. In addition, levels of the dopamine D4 receptor have been reported to be elevated in schizophrenic patients (See an y_ otros Nature, 1993, 365, 441) and antipsychotic clozopine which lacks side effects ext rapiramidales, it has a high affinity with the dopamine D4 receptors (Van Tol, et al., Nature, 1991, 350, 610). Several effects are known with respect to the compounds, which are ligatures in the different subtypes of serotonin receptors. Regarding the 5-HT2A receptor, which was previously referred to as 5-HT2, the following effects have been reported, for example: Antidepressant effect and improvement of sleep quality (Meert, T. F .; Jansen, PAJ Drug Dev. Res. 1989, 18, 119) and negative symptoms of schizophrenia and reduction of collateral effects ext rapiramidales caused by treatment with classical neuroleptics in schizophrenic patients (Gelders, YG, Brithis J: Psychiatry, 1989, 155 (Suppl 5, 33) Finally, selective 5-HT2A antagonists could be effective in the prophylaxis and treatment of migraine (Scrip Report, "Migraine - Current trends in researc and treatment" (Migraine - current trends in research and treatment), PJB Publications Ltd. May 1991) Clinical studies have shown that partial 5-HT1A agonists are useful in the treatment of anxiety disorders., such as generalized anxiety, anxiety disorders, panic disorders, and obsessive compulsive disorders (Glitz D: A :, Pohl, R., Drugs 1991, 41, 11). Preclinical studies have shown that complete agonists are also useful in the treatment of the above-mentioned anxiety disorders (Schiper, Human Psychopharmacol. (Ps i cofarmacol.Humana, 1991, 6, S53) .There are also tests, both clinical and Preclinical studies supporting the beneficial effect of partial agonists d'e 5-HT1A in the treatment of depression, impulse control disorders and alcohol abuse (van Hest, Psychopharmacol., 1992, 107, 474; Schiper et al., Human Ps ichopharmacol. (s icof armacologí a Humana), 1991, 6, S53; Cervo et al., Eur. J. Pharm., 1988, 158, 53; Glitz and Pol. , Drugs 1991, 41, 11; Grof et al., Int. Clin. Psychopharmacol., 1992, 8, 167-172; Ansseau et al., Human Psychopharmacol., 1993, 8, 279-283). The agonists and partial agonists of 5-HT1A inhibit the aggression induced by isolation in male mice, indicating that these compounds are useful in the treatment of aggression (Sánchez et al., Psychopharmacology, 1993, 110, 53-59). In addition, it has been reported that the ligatures of5-HT1A show an antipsychotic effect in animal models (Wadenberg and Ahlenius, J. Neural Transm., 1991), 83, 43; Ahlenius, Pharmacol. & Toxicol., 1989, 64; Lowe et al., J. Med. Chem. (Quim. Med. Report) 1991, 34, 1860; New et al. J. Med. Chem. 1989m 32,1147; and Martín et al., J. Med. Chem, 1989, 32, 1052). Recent studies also indicate that 5-HT1A receptors are important in the serotorgénic modulation of haloperidol-induced catalepsy (Hicks Life Science 1990, 47, 1609, Wadenberg et al., Pharmacol. Biochem. &Behav. (Conducta y Bioqulm. .) 1994, 47, 509-513), suggesting that 5-HT 1A agonists are useful in the treatment of EPS induced by conventional antipsychotic agents such as haloperidol. 5-HT1A agonists have demonstrated neuroprotective properties in rodent models of focal and global cerebral ischemia and can, therefore, be useful in the treatment of ischemic pathologies (Prehn, Eur. J. Pharm., 1991, 203, 213). . Pharmacological studies have been presented indicating that 5-HT 1A antagonists are useful in the treatment of senile dementia (Bowen et al., Trends Neur. (Tendencies Neur.) Sci., 1992,15, 84). 5-HT reuptake inhibitors are well-known antidepressant drugs. Accordingly, ligations for dopamine D4 receptors are potential drugs for the treatment of psychosis and positive symptoms of schizophrenia and compounds with combined effects on dopamine D4 and 5-HT1A receptors and / or 5-HT transporter may have the benefit additional effects on other psychiatric symptoms in schizophrenic patients, such as depressive and anxiety symptoms. As the classes of compounds for binding of 5-HT1A and 5-HT2A receptors and inhibitors of 5-HT reabsorption have different activities in different animal models that predict anxiolytic and anti-aggressive effects (Perregaard et al., Recent Developments in Anxiolytics (Recent Developments in anxiolytics) Current Opinion in Therapeutic Patents (Current opinion in therapeutic patents), 1993, 1, 101-128) and / or in models that predict the effects in other psychotic disorders, could also be highly beneficial to have such combined effects serotogérnicos Brief Description of the Invention The object of the invention is to provide compounds with activities of dopamine D4 or with combined effects of dopamine receptors D4_ 5-HT receptors and / or 5-HT transporter. It has been found that certain substituted indane or dihydroindole compounds have effects on dopamine D4 receptors. In addition, many of the compounds interact with serotonin receptors, in particular, with 5-HT1A and / or 5-HT2A receptors and / or act as inhibitors of 5-HT reuptake. Accordingly, the present invention relates to novel compounds of the formula I where A is a group Y is a hydrocarbon group that completes an indane ring, an NR1 group that completes a dihydroindole ring or an N group, which completes a dihydroindole ring bound via position 1; -W is a bond and n + m is 1, 2, 3, 4, 5, or 6: • W is CO, SO, or S02, n is 2, 3, 4, or 5 and m is 0, 1, 2 or 3 provided that n + m is not more than 6; or • W is O, S, n is 2, 3, 4, or 5 and m is 0, 1, 2 or 3, provided that n + m is not more than 6; and when Y is N completing a hydroindol ring bound to position 1, then m is 2 or 3 and when Y is NR1 completing a dihydroindole ring bound via position 2, then m is 1, 2, or 3, the line of points, emanating from X, indicates an optional link; when it does not indicate a link X is N, CH or COH; and when it indicates a link X is C; R1 is: • hydrogen, alkyl (in / in) and cycloalkyl (alen / in) yl C3.8, cycloalk (in / in) i lo C3_s-alk (in / in) yl C1. e, aryl, heteroaryl, aryl, C 1-6 alkyl, cyclohexyl, thioacyl, alkylsulfonyl, c-, trifluoromethyl-sulfonyl, aryl sulphonyl, or heteroaryl sulphonyl. . -R15 VCO where V is O or S and R15 is a Iqu (in / in) i lo C-L.g, cycloalk (en / in) yl C3.8, cycloalk (en / in) yl C3.8-alkyl (in / C1_6), aryl, heteroaryl, or • a group R16 R17 NCO- or R1S R17 NCS- where R16 and R17 are independently hydrogen, alkyl (in / in) i C ^ j, cycloalk (en) i lo C3.8, cycloalk (en) yl C3_8-alkyl (en / in) yl C6, aryl, heteroaryl; or R1S and R17 together with the N- atom, to which they themselves they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepine group, and R2 and R5 are independently selected from hydrogen, halogen, cyano, nitroalkyl (en / in) i lo C1.6, alkoxy C ^ s, alkylthio C1- 6, hydroxy, cycloalk (en) i lo C3.8, c ic loalqu (en) i lo C3.8-alk (in / in) yl alkylcarbonyl C * .s, phenyl Icarboni lo, phenyl Icarboni substituted halogen, trif luorme ti lo, trif luorme ti 1 sul fi oni loxi and alkylsulfonyl one of R 'R5 being alternatively a group - NR13 R14 where R13, as defined for R1 and R14, is hydrogen, alk (in / in) i lo C 1 e, cic loalqu (en) ilo C3-8, c ic loalqu (en) i lo C3.8 -alqu (in / in) i lo C1. β, aryl, heteroaryl; aryl-C 1-6 alkyl or heteroaryl-alkyl or R 13 and R 14 together with the N- atom, to which they are attached form a group where Q is C = 0, C = S or CH 2; T is NH, N-alkyl, S, O or / (CHJb CH2 and p is 1-4, inclusive, or two adjacent groups taken from R2 R5 can join and designate a - (CH2) 3-or -CH = CH-NH, forming a 5-membered fused ring. R6-R9 and R11-R12 are, independently, hydrogen, halogen, cyano, nitro alk (in / in) i lo C. alkoxy-6'-alkylthio C1- (hydroxy cycloalkyl (en) i lo C3.8, cycloalk (en) yl C-alk (en / in) yl C1-6, aryl, heteroaryl, f-enylcarbonyl, f-enylcarboni-halogen substituted , trifluoromethyl, or C1-alkylsulfonyl, or two adjacent groups taken from Rd-R9 can together form a methylenedioxy group, R10 is as defined for R1, above, except that the substituent R3 or R4 in the position 6 can not be -NR13 R14 when Y is CH2, W is a bond, n + m is 1 and the ring is linked via the 1- position, or a pharmaceutically acceptable acid addition salt thereof The compounds of the invention They demonstrate a high affinity for dopamine D4 receptors and it was further found that some of the compounds also show affinity for serotonergic receptors including 5-HT1A and / or 5-HT2A receptors, apart from the effects of these subtypes of receptors, certain compounds of the present compounds also demonstrate n an inhibitory effect of 5-HT reabsorption. Accordingly, the compounds of the invention are considered useful in the treatment of positive and negative symptoms of schizophrenia, other psychoses, anxiety disorders, such as generalized anxiety disorder, panic disorder and obsessive compulsive disorder, depression, abuse of alcohol, disorders to control impulses, aggression, side effects induced by conventional antipsychotic agents, ischemic pathological states, migraine, senile dementia, and cardiovascular disorders and for the improvement of sleep. In another aspect the invention provides a pharmaceutical composition comprising at least one compound of formula 1, as defined above or a pharmaceutically acceptable addition salt thereof in a therapeutically effective amount and in combination with one or more carriers or diluents pharmaceutically acceptable In another aspect, the present invention provides the use of a compound of formula 1, as defined above or an acid addition salt thereof for the manufacture of a pharmaceutical preparation for the treatment of the above-mentioned disorders.

Detailed Description of the Invention Some of the compounds of the general formula I exist as optical isomers and said optical isomers are also included in the present invention. The expression "alkyl (en / in) yl C6" means that the group can be a C6 alkyl group. C2.6 alkenyl or C2.6 alkynyl. The expression c ic loa Iqu (en) i lo C3-ß, means a C3.8 cycloalkyl group or a C3.8 cycloalkenyl group. The term "Cx_6 alkyl" refers to a branched or unbranched alkyl group, which has from one to six carbon atoms, inclusive, such as methyl, ethyl, 1-propyl, 2-propyl, 1-butyl, 2-butyl, 2-metyl-2-propyl and 2-methyl-1-propyl. Similarly C2_6 alkenyl, alkynyl C2"s, respectively, designate said groups having from two to six carbon atoms, inclusive. Preferred groups are those having from two to four carbon atoms. The terms Cx.6 alkoxy, C1_6 alkylthio, alkylsulfonyl < 7 i _ e, alkylamino Cx.6, alkylcarbonyl C. e, designate said groups wherein the alkyl group is alkyl C ^ j, as defined above. The term C3-8 cycloalkenyl designates a carbocycle, monocyclic or bicyclic, having from three to eight C- atoms, such as cyclopropyl, cyclopentyl, cyclohexyl, etc. The term "C3.8 cycloalkenyl" refers to a carbocycle, monocyclic or bicyclic, having from three to eight C-atoms, containing a double bond. The term "aryl" refers to a carbocyclic aromatic group, such as phenyl, naphthyl, in particular phenyl, including naphthyl or substituted methyl phenyl. The term "heteroaryl" refers to a heterocyclic, mono- or bicyclic group, such as indolyl, thienyl, pyrimidyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, imidazolyl, benzofuranyl, benzothienyl, pyridyl, and furanyl, especially pyrimidyl, indolyl and thienyl. Halogen means fluorine, chlorine, bromine or iodine. As used herein, the term "acyl" refers to a formyl, alk (in / in) and Icarbonyl C1-6, arylcarbonyl, aryl-alk (in / in) and 1-carbonyl group. c ic loalqu (en) i 1 -carbonyl C3.8, ocic loalqu (en) i 1-carboni lo C3.8-alk (en / in) ilo Cx. β, and the term thioacyl is the corresponding acyl group in which the carbonyl group is replaced with a thiocarbonyl group. A group of compounds, according to the invention, are compounds wherein Y is CH2 by completing an indane ring. Another group of compounds, according to the present invention, are the compounds wherein Y is NRX or N by completing a dihydroindole ring, which is adhered via position 1, 2 or 3 to the group (CH2) m-W- (CH2) n. As indicated in formulas 1, a), b) and c), the rings may have variable adhesion points. So a) can. be linked to X via position 2- or 3- and c) via position 4-, 5-, 6- or 7- Therefore, other groups of compounds, according to the present invention, are compounds where Y is CH2 and A is a group a), compounds where Y is CH2 and A is a group b) and compounds where Y is CH2 and A is a group C) . Based on the variability of the adhesion points in both indane and indole rings, other subgroups of compounds have been prepared.

Said subgroups are specifically set forth in the Claims. Still other groups of compounds, according to the present invention, are compounds where Y is NR1 or N and A is a group a), compounds where Y is NR1 or N and A is a group b) and compounds where Y is NR1 or N and A is a group c). Based on the variability of the adhesion points in both indane and indole rings, other subgroups of compounds have been prepared. Said subgroups are specifically set forth in the Claims. A preferred group of compounds are compounds wherein A is a group a). In a group of compounds where W is a bond, n + m is from 1 to 4, on + m is selected from part 1 and 2. Other groups of compounds are compounds where n + m is from 2 to 6, 2 to 4, 3 to 6 or 3 to 4. Where W is not a bond, O or CO In a subclass of compounds X is C. In another subclass of compounds X is CH In another subclass of compounds X is N.

A subclass of compounds are those where Y is CH2, the resulting indane ring being linked via the 2- position. A is a structure a), W is a bond and n + m is 1-4 or m + l is 1 to 2. In another subclass of compounds Y is CH2, the resulting indane ring being linked via position 1- . A is a structure a), W is a bond and n + m is 1-4 or m + l is 1 to 2. In another subclass of compounds Y is NR1 or N and A is a structure a), W is a link and n + m is 1-4 on + m is 1 or 2 y. X is C. R1 is preferably selected from hydrogen, C1-6 alkyl, formyl, alkylcarbonyl C? _ or C 1_6 alkylaminocarbonyl. R2 to R5 are preferably selected from hydrogen, halogen, cyano, nitro, C6 alkyl, C1-6 alkoxy. CX.6 alkylthio, hydroxy, C3. cycloalkyl, C3.6 cycloalkyl, Cx.6 alkyl, CL.alkylcarbonyl, f.silcarylcarbonyl, phenylcarbonyl, substituted halogen, trifluoromethyl, trifluoromethyl sulfonyl, alkylsulfonyl Cx_6; one being from R2 to Rs alternatively a group -NR13 R14, wherein R13 is hydrogen, C1-s alkyl, acyl, C 1.2 alkylsulfonyl, or a group -R16 R17 NCO-, wherein R1S is hydrogen, Cx.6 alkyl, C3 cycloalkyl .8, C3.8 cycloalkyl-Cx.sub.4 alkyl, or aryl, and, R17 is hydrogen or C1.6alkyl, or R16 and R17 together with the N- atom to which they are linked, form a pyrrolidinyl group , piperidinyl or perhydroazepine; and R14 is hydrogen or CX.G alkyl, or R13 and R14 are joined to form a pyrrolidinyl, piperidinyl or perhydroazepine group or an unsubstituted lactam ring of 5 to 7 members or more preferably R2 to R5 are selected from hydrogen , halogen, cyano, methoxy, propyloxy or -NR 13 R 14, wherein R 13 is formyl, acetyl, me thi laminocarbonyl, methylaminothiocarbonyl, dimethyl-laminocarbonyl, dimethylaminothiocarbonyl, methylsulfonyl, aminocarbonyl, cyclopropylcarbonyl, methyl, pyrrolidinylcarbonyl or - Fluorine phenylaminocarboni and R14 is hydrogen or C1.6alkyl. Another subclass of compounds of the invention are those wherein one of R2-R5 is a group -NR13 R14. Even in another subclass of compounds of the invention none of R2-R5 is a group -NR13 R14.

Another preferred group of compounds, according to the present invention, are compounds where two adjacent groups taken from R2 to R5 join and designate -CH = CH-NH-, thus forming a ring of 5 fused members. R6 to R9 are preferably selected from hydrogen, halogen, cyano, nitro, Cx.6 alkyl, C2.g alkoxy, alkylthio hydroxy, C3.8 cycloalkyl C3.8 cycloalkyl C1-s alkyl, aryl, phenylcarbonyl, phenylcarboni substituted halogen, trif lumethyl, or alkylsulphyl C1-s or two adjacent groups taken from Rs-R9 can be joined and designate a methylenedioxy group. More preferably, Rs to R9 are selected from hydrogen, halogen, C1.6alkyl, C2.g alkoxy, or two adjacent groups taken from Rs a R9 can be attached and designate a methylenedioxy group. R11 and R12 are preferably hydrogen, or C 1 ß alkyl or more preferably hydrogen or methyl. R10 is preferably hydrogen, or alkyl Acyl or more preferably hydrogen, methyl, or acetyl. Preferred compounds are compounds selected from: 6-chloro-3- [1- (6-bromo-l-indanylmethyl) -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, - [1- (1-indanylmethyl) -l, 2,3,6-tetrahydropyridin-4-yl] - lH-indole, 3- [1- (1-indanylmethyl) piperidin-4-yl] -lH-indole , 6-chloro-3- [1- (7-methoxyindan-1-yl) methyl-1, 2,3,6-tetrahydropyridin-4-yl] -IH-indole, oxalate of 3 - [1 - (6 - met oxy-indan-1-i 1) me ti 1 - 1, 2, 3, 6 -tet rahidropyridin-4-i 1] -lH-indole, 6-chloro-3- [1- (6-cyano-l- indanylmethyl) -1,2,3,6-tetrahydrohyd id idin-4-i 1] -lH-indole, 6-chloro-3- [1- (6-cyano-l-indanylmethyl) -piperidin-4- il] -lH-indole, 6-chloro-3- [1- (4-acetylamino-l-indanylmethyl) -1, 2, 3, 6 -ethehydropyridin-4-yl] -IH-indole, 6-chloro- 3- [1- (5-acetylamino-l-indanylmethyl) -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 6-chloro-3- [1- (6-bromo-l- indanylmethyl) -1,2, 3,6-tetrahydrohyd id idin-4-i 1] - ÍH-indole, 6-chloro-3- [1- [2-indan-1-yl] ethyl-1,2 , 3, 6-tetrahydro-p go idin-4-i 1] -lH-indole, 5-fluoro-3- [1- [2- (indan-1-yl) ethyl] -1,2,3,6-tetra-hydropyridin-4-i 1] -lH-indole, 5-fluoro-3- [1- [2- (indan-1-yl) ethyl] -piperidin-4-yl] -IH-indole, 5-fluoro-3- [1- [ 4- (indan-1-yl) utan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 5-f luor-3- [1- [4- (indan -1-yl) butan-1-yl] -piperidin-4-yl] -lH-indole, 6-fluoro-3- [1- [4- (indan-1-yl) butan-1-yl] -piperidine -4 il] -lH-indole, 6-chloro-3- [1- [3- (indan-1-yl) propan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] - lH-indole, 6-chloro-3- [1- [4- (indan-1-yl) butan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, -chloro-3- [1- (indan-2-yl) methyl-l, 2,3,6-tetrahydro-pyridin-4-yl] -lH-indole, 3- [1- (indan-2-yl ) methyl-l, 2,3,6-tetrahydropyridin-4-yl] -lH-indole, 7-chloro-3- [1- (indan-2-yl) methyl-1,2,3,6-tetrahydro- pir idin-4-i 1] -lH-indole, S, 7-dichloro-3- [1- (indan-2-yl) methyl-1, 2,3,6-tetrahydropyr idin-4-i 1 ] -lH-indole, 3- [1- (indan-2-yl) methyl-1, 2,3,6-tetrahydropyridin-4-yl] -5 , 6-methylenedioxy-lH-indole, 5- [4- (indan-2-yl) methyl-piperazin-1-yl] -lH-indole, 6-Chloro-3- [1- [2- (indan-2-yl) ethyl] -1,2,3,6-tetra-hydropyridin-4-yl] -lH-indole, 6-chloro-3- [1- [3- (indan-2-yl) propan-l-yl] -1,2,3,6-tetrahydropyridin-4-yl] -IH-indole, 6-chloro-3- [1- [4 - (indan-2-yl) butan-l-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 3- [1- [4- (2-propyl) oxyindan-2 -yl) methyl] piperidin-4-yl] -6-chloro-lH-indole, 4 [4- (6-chloro-lH-indol-3-yl) -1,2,3,6-tetrahydro-pyridin- 1-ylmethyl] -1,4,5,6, -tetrahydrocyclopent [e] indole, 6-chloro-3- [1- (4-acetylarainodandan-2-yl) methyl-1, 2, 3, and tetrahydropyridin-4 - il] -lH-indole, 6-chloro-3- [1- (4-acetylaminoindan-2-yl) methylpyridin-4-yl] -IH-indole, 6-chloro-3- [1- [2- ( 6-acetylaminoindan-1-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 6-chloro-3- [1- [3- (6-acetylaminoindan-1-yl) ) ropan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 6-chloro-3- [1- [4- (6-acetyl-laminoindan-1-yl) butan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 3- [1- (5-acetylaminoindan-2-yl) -Retyl-l, 2, 3,6-tetra-hi-drop-ir-id-4-i-1] -6-c-loro-IH-indo 1, 3- [1- (5-acetylaminoindan-2-yl) methylpiperid-4-yl] -6-chloro-lH-indole, 3- [1- [2- (l-acetyl-2,3-dihydro-IH-indole- 3-yl) ethyl] -1,2,3,6-tetra-idropyridin-4-yl] -6-chloro-lH-indole, 3- [1- [2- (l-acetyl-2,3-dihydro- ÍH-indo 1-3 -yl) ethyl] -piperidin-4-yl] -6-chloro-lH-indole, 6-chloro-3- [1- [2- (l-formyl-2,3-dihydro- lH-indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -IH-indole, 6-chloro-3- [1- [2- (1-formyl-2, 3 -dihydro-lH-indol-3-yl) ethyl] piperidin-4-yl] -IH-indole, 3- [1- [2- (l-acetyl-5-bromo-2, 3-dihydro-IH-indo 1-3 -yl) ethyl] 1, 2, 3, 6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 3- [1- [2- (l-acetyl-2,3-dihydro- 1H-indol-3-yl) ethyl] -1, 2, 3, d-tetrahydropyridin-4-yl] -7-chloro-lH-indole, 3- [1- [2- (1-acetyl-2,3-dihydro-1H-indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -6, 7- dichloro-lH-indole, 3- [1- [2- (l-acetyl-2,3-dihydro-lH-indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -5,6-methylenedioxy-lH-indole, 3- [1- [2- (l-tert-butoxycarbonyl-2,3-dihydro-lH-indol-3-yl) ethyl] -1,2,3, d -tetraropyridin-4-yl] -6-chloro-1H-indole, 5- [4- [2- (l-acetyl-2,3-dihydro-lH-indol-3-yl) ethyl] -piperac in - 1-yl] -lH-indole, 3- [1- [3- (l-acetyl-2,3-dihydro-lH-indol-3-yl) propan-1-yl] -1,2,3, 6 -tetrahydropyridin-4-yl] -6-chloro-lH-indo 1, 3- [1- [2- (l-acetyl-5-fluoro-2,3-dihydro-1H-indol-3-yl) et il ] -l, 2,3,6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 3- [1- [2- (l-acetyl-5-methyl-2,3-dihydroxy) -indol-3-yl) ethyl] -l, 2,3,6-tetrahydropyridin-4-yl] -6-chloro-lH-indo, 1,6-chloro-3- [1- (indane-2-ylmethyl) piperidin-4-yl] - 1 H -indole, 3- [1- (indan-2-ylmethyl) piperidin-4-yl] -IH-indole, 7-chloro-3- [1- (indane-2-ylmethyl) piperidin-4-yl] - 1H -ind ol, 6, 7-dichloro-3- [1- (indan-2-ylmethyl) iperidin-4-yl] -IH-indole, 3- [1- (indan-2-ylmethyl) piperidin-4-yl] -5, 6-methylene-dioxy-1H-indole, 6-chloro-3- [1- [2- (indan-2-yl) ethyl] piperidin-4-yl] - 1H-indole, 6-chloro-3- [1 - [3- (indan-2-yl) propan-3-yl] piperidin-4-yl] - Indole-indole, 6-chloro-3- [1- [4- (indan-2-yl) butan-4 -yl] piperidin-4-yl] -Iff-indole, 4- [4- [2- (indan-2-yl) ethyl] piperazin-1-yl] -IH-indole, 5- [4- [2- (indan-2-yl) ethyl] piperazin-1-yl] -IH-indole, 5-chloro-l- [1- [2- (indan-2-yl) ethyl] -1,2,3,6- tetrahydropyridin-4-yl] -lE-indole, 1- [1- [2- (indan-2-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] - Iff-indole, 2- [1- [2- (indan-2-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] - Iff-indole, 5-chloro-l- [1- [2- (inda- 2-yl) ethyl] -piperidin-4-yl] -lH-indole, 1- [1- [2- (indan-2-yl) ethyl] -pyridin-4-yl] -IH-indole, 6-chloro -3- [1- [2- (2, 3-dihydro-ÍH-indo 1 -3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 6-chloro -3- [1- [4- (2,3-dihydro-ÍH - indo 1 - 3 -yl) butyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] -IH-indole, 6-chloro-3- [1- [2- (2,3-dihydro-1 -me ti laminocarboni 1-lH-indol-3-yl) ethyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] IH-indole, (+) - (3- [1- [2- (1-acetyl-2,3-dihydro-1H-indol-3-yl) -ethyl] -l, 2,3,6-tetrahydropyridin- 4-yl] -6-chloro-lH-indo 1, (-) - (3- [1- [2- (l-acetyl-2,3-dihydro-lH-indol-3-yl) -ethyl] - 1,2,3,6-tetrahydropyridin-4-yl] -6-chloro-lff-indo 1, 3- [1- [4- (l-acetyl-2,3-dihydro-lH-indol-3-yl ) butyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 6-chloro-3- [1- [6-chloro-l-indanylmethyl] -1,2, 3,6-tetrahydropyridin-4-yl] -lfi-indole, 6-chloro-3- [1- [6-nitro-l-indanylmethyl] -1,2,3,6-tet rahidropir idin-4-yl] -IH-indole, 6-chloro-3- [1- [6-fluoro-l-indanylmethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lfi-indole, 6-chloro-3- [ 1- [5-Chloro-1-indanylmethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 6-chloro-3- [1- [6-methyl-1-indanylmethyl] - 1,2,3,6-tetrahydropyr idin-4-yl] -lfi-indole, 6-c lo or -3- [1- (1-indanylmethyl) -1,2,3,6-tetrahydro-p go idin- 4 - i 1] - me ti 1 - Ifí-indole, ß-chloro-3- [1- (1-indanylmethyl) - 1, 2, 3, 6-tetrahydro-pyridin-4-yl] -1 - (2-pro pIL-lH-indole, 5-fluoro-3- [1- [6- (trifluoromethyl) -1-indanylmethyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] -lH-indole, -fluor-3- [1- [5- (trifluoromethyl sulfophenyloxy) -1-inda-nylmethyl] - 1, 2, 3, 6-tet rahydropyr idin- 4 -i 1] -lfi-indole, 6-chloro- 3- [1- [1-indanylmethyloxyethyl-1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 5-fluoro-3- [1- [6- (1-indan-l- il) -hexan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 3- [1- [2- (l-acetyl-5-fluoro-2,3- dihydro-lH-indol-3-yl) ethyl] -piperidin-4-yl] -6-chloro-l-yl-indole, 6-chloro-3- [1- [2- (l-formyl-5-f) 2,3-dihydro-lH-indol-3-yl) ethyl] -1,2,3, β-tetrahydropyridin-4-yl] -1H-indole, 6-chloro-3- [1- [2- (5 -fluor-2, 3-dihydro-lH-indol-3-yl) -ethyl] -l, 2,3,6-tetrahydropyridin-4-yl] -lfi-indole, 6-chloro-3- [1- [ 2- (5-Fluoro-2,3-dihydro-l-methylaminocarbonyl-1-yl-indol-3-yl) ethyl] 1, 2,3,6-tetrahydropyr idin-4-yl] -lfi-indole, 6-chloro-3- [1- [2- (2,3-dihydro-l-mesylaminocarbonyl-lH-indole-3- il) ethyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] lH-indole, 6-chloro-3- [1- [2- (5-f luor-2, 3-dihydro-l-mesylamino -carbonyl-lH-indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 3- [1- [(1-acetyl-2,3-dihydro- lH-indol-2-yl) methyl] -1,2,3,6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 3- [1- [(l-acetyl-5-fluoro-2 , 3-dihydro-lH-indol-2-yl) -methyl] -1,2,3,6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 3- [1- [(l-acetyl -2, 3-dihydro-lH-indol-2-yl) methyl] -piperidin-4-yl] -6-chloro-lH-indole, 3- [1- [2- (l-acetyl-2, 3- dihydro-lH-indol-2-yl) ethyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 3- [1- [2- (l-acetyl-5 -fluor-2,3-dihydro-lH-indol-2-yl) ethyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] -6-chloro-lH-indo 1, 3- [1- [ 2- (1-acetyl-2, 3-dihydro-1H-indol-2-yl) ethyl] -piperidin-4-yl] -6-c-loro-1H-indole, 6-chloro-3- [1- [ 2- (2,3-dihydro-lH-indole-2- il) ethyl] -1, 2, 3, 6-tetrahydropyridin-4-yl] -IH-indole, 6-chloro-3- [1- [2- (5-f luor-2, 3-dihydro-lH- indol-2-yl) -ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 6-chloro-2- [4- [(indan-2-yl) methyl] -piperacin -1-yl] -IH-indole, 6-chloro-2- [4- [2- (indan-2-yl) ethyl] -piperazin-1-yl] -lH-indole, 2- [4- [2 - (L-acetyl-2,3-dihydro-lH-indol-3-yl) ethyl] -piperazin-1-yl] -6-chloro-lH-indl, 2- [4- [2- (l-acetyl -5-fluor-2,3-dihydro-lH-indol-3-yl) ethyl] -piperazin-1-yl] -6-chloro-lH-indole, 6-chloro-3- [4- [(indan- 2-yl) methyl] -piperazin-1-yl] - 1H-indole, 6-chloro-3- [4- [2- (indan-2-yl) ethyl] -piperazin-1-yl] -lH-indole 3- [4- [2- (1-acetyl-2,3-dihydro-1H-indol-3-yl) ethyl] -piperazin-1-yl] -6-chloro-1H-indole, 3- [4 - [2- (1-acetyl-5-fluoro-2,3-dihydro-1H-indol-3-yl) ethyl] -piperazin-1-yl] -6-chloro-lH-indole, 4- [4- [(indan-2-yl) methyl] -piperazin-1-yJL] -lH-indole, 4- [4- [2- (l-acetyl-2,3-dihydro-lH-indol-3-yl) ethyl] -piperazin-1-yl] -lH-indole, 4- [4- [2- (l-acetyl-5- fluor-2, 3-dihydro-lH-indol-3-yl) ethyl] -piperazin-1-yl] -lH-indole, 7- [4- [(Indan-2-yl) methyl] -piperazin-1 il] -IH-indole, 7- [4- [2 (Indan-2-yl) ethyl] -piperazin-1-yl] -lH-indole, 7- [4- [2- (1-acetyl-2, 3-dihydro-lH-indol-3-yl) ethyl] -piperazin-1-yl] -IH-indole, 7- [4- [2- (l-acetyl-5-fluoro-2,3-dihydro-IH - indol-3-yl) ethyl] -piperazin-1-yl] -lH-indole, 2- [1- [2- (l-acetyl-2,3-dihydro-lH-indol-3-yl) ethyl] - 1, 2, 3, 6-tetrahydropyridin-4-yl] -lH-indole, 2- [1- [2- (1-acetyl-2, 3-dihydro-1H-indol-3-yl) ethyl] - 1, 2, 3, 6-tetrahydropyridin-4-yl] -5-chloro-lH-indole, 2- [1- [2- (1-acetyl-2, 3-dihydro-1 H -indol-3-yl) ethyl] -piperidin-1] -lH-indole, 2- [1- [2- ( l-acetyl-2,3-dihydro-lH-indol-3-yl) ethyl] -p iper idin-4-i 1] - 5-c loro-ÍH-indole, 2- [1- (indan-2- il) methyl-l, 2,3,6-tetrahydropyridin-4-yl] - lH-indole, 5-chloro-2- [1- (indan-2-yl) methyl-1, 2,3,6-tetrahydro -p ir idin- 4-i 1] -lH-indole, 5-chloro-2- [1- [2- (indan-2-yl) ethyl-1, 2, 3, 6-tetrahydro pyridin-4-yl ] -lH-indole, 2- [1- (indan-2-yl) methylpiperidin-4-yl] -lH-indole, -Chloro-2- [1- (indan-2-yl) methylpiperidin-4-yl] - 1 H -indole, 2- [1- [2- (indan-2-yl) ethylpiperidin-4-yl] -lH -indol, -chloro-2- [1- [2- (indan-2-yl) ethylpiperidin-4-yl] - 1 H -indole, 7 - [4 - [(6-c-lOR-IH-indol-3-yl) -1, 2, 3, 6-tetrahydro-pyrid-1-yl] -methyl] -3,6, 7, 8, tetrahydrocyclopent [e] indole, 7- [4- [(6-chloro-1H-indole - 3 -yl) -1,2,3,6-tetrahydro-pyrid-1-yl] -methyl] -1,5,6,7-tetrahydrocyclopent [f] indole, 6- [4- [(6-chloro- lH-indol-3-yl) -1,2,3,6-tetrahydro-pyrid-1-yl] -methyl] -1,6,7,8, tetrahydrocyclopent [g] indo 1, 7- [4 - [ (6-chloro-lH-indol-3-yl) -1,2,3,6-tetrahydropyrid-1-yl] -methyl] -1, 6, 7, 8-t and rahidrociclopent [g] indole, (+ ) 6-chloro-3- [1- [2- (2,3-dihydro-1-yl-indol-3-yl) ethyl] 1, 2, 3, 6-tetrahydropyridin-4-yl] -Ifl-indole, 6 -chloro-3- [1- [2- (2, 3-dihydro-lH-indol-1-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -Ifl-indole, 6- chloro-3- [1- [2- (2,3-dihydro-1-yl-indol-1-yl) ethyl] -piperidin-4-yl] - Ifl-indole, 6-chloro-3- [1- [3 - (2,3-dihydro-1-yl-indol-1-yl) propan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -Ifl-indole, 6-chloro-3- [1- [4- (2 , 3-dihydro-IH-indol-1-yl) butan-1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 6-chloro-3- [l- [3 - (2,3-dihydro-1H-indol-1-y1) -3-oxopropan-1-yl] -1, 2, 3, 6-tet rahydropi id-4-i 1] -1H-indole, 3 - [1- [(5- (2-propyl) oxyindan-2-yl) methyl] piperidin-4-yl] -6-chloro-1-yl-indole, 3- [1- [(5,6-dimethoxyindan-2 -yl) oxyindan-2-yl) methyl] -piperidin-4-yl] -6-chloro-l-yl-indole, 3- [1- [(4- (2-propyl) oxyindan-l-yl) methyl] piperidin -4-yl] -6-chloro-Indole-indole, 3- [1- [(5- (2-propyl) oxyindan-1-yl) methyl] piperidin-4-yl] -6-chloro-1H-indole , 3- [1- [(7-Raetoxyindan-1-yl) ethyl] piperidin-4-yl] -6-chloro-1-yl-indole, 3- [1- [(5,6-dimethoxyindan-1-yl) methyl] piperidin-4-yl] 6-chloro-1H-indole, 3- [1- [(4- (2-propyl) oxyindan-2-yl) methyl] -1,2,3,6-tetrahydropyridin-4 -yl] -6-chloro-lH-indole, 3- [1- [(5- (2-propyl) oxyindan-2-yl) methyl] -1,2,3,6-tetrahydropyridin-4-yl] - 6-chloro- Ifi-indole, 3- [1- [(5,6-dimethoxyindan-2-yl) methyl] -1,2,3,6-t etra-hydropyridin-4-yl] -6-chloro-lH-indole, 3- [1- [(4- (2-propyl) oxyindan-1-yl) methyl] -1, 2, 3, 6-tetrahydropyridin- 4-yl] -6-chloro-1-yl-indole, 3- [1- [(5- (2-propyl) oxyindan-1-yl) methyl] -1,2,3,6-tetrahydropyridin-4-yl] - 6 - chloro - η H - indole, 3- [1- [(7-methoxyindan-1-yl) ethyl] -1,2,3,6-tetrahydro pyridin-4-yl] - 6-chloro indole, 3- [1- [(5,6-dimethoxyindan-1-yl) methyl] -1,2,3,6-t and rahydropyr idin-4-yl] -6-chloro-1 H- indole, or 3- [4- [(5,6-Dimethoxyindan-1-yl) methyl] -piperazin-1-yl] -6-chloro-1-yl-indole, and acid-addition salts are arcibly acceptable therefrom. The acid addition salts of the present invention are pharmaceutically acceptable salts of the compounds of formula I, formed with non-toxic acids. Examples of said organic salts are those with the following acids: maleic, fumaric, benzoic, ascorbic, succinic, oxalic, bi-methyl-lysalonic, methanesulfonic, ethanedisulonic, acetic, propionic, tartaric, salicylic, citric, gluconic, lactic, malic, mandelic, cinnamic, citraconic, aspartic, spherical, palmitic, itaconic, glycolic, p-aminobenzoic, glutamic, benzenesulfonic and acetic theophylline, as well as 8-halot eof il inas, for example bromot eof il ina. Examples of said inorganic salts are those with hydrochloric, hydrobromic, sulfuric, sulfamic acids, phosphoric and nitric. The pharmaceutical compositions of this invention or those that are manufactured according to the present invention, can be administered by any suitable route, for example, orally in tablets, capsules, powders, syrups, etc. , or in paranteral form in the form of solutions for injection. To prepare such compositions, methods well known in the art can be used, and pharmaceutically acceptable carriers, diluents, excipients or other additives normally used can be used. Conveniently, the compounds of this invention are administered in unit dose form containing said compounds in an amount of about 0.01 to 100 mg. The total daily dose is generally about 0.05-500 mg. and more preferably about 0.1 to 50 mg. of the active compound of the invention. The compounds of the invention can be prepared in the following manner: 1) Alkylation of a piperazine, piperidine or t-e rahydropyridine of the formula 11 with an alkylation derivative of the formula III: where R2-R5, X, Y, A, n, m, W and the dotted line are as defined above, and L is a leaving group, such as, for example, halogen, mesylate or tosylate. 2) Reduction of the carbonyl amide in a compound of the following formula IV: where R2-RS, X, Y, A, m, W and the dotted line are as defined above, and n is 1, 2, 3, 4, or 5; 3) Introduction of a substituent R2, R3, R4 ', or R5', by reaction of a compound of the following formula V: wherein one of R2 R5, is hydrogen and the others are the corresponding R2, R3, R4, or R5 ', as previously defined and X, Y, A, m, n, W, and the dotted line, are, as previously defined, using a reactive agent such as a halogen or a halogenating agent, a sulfonating agent, a nitrating agent or a reactive agent generating ions of carbonium (RCO *, R +) where R is alkyl, alkynyl, arylchloralkyl, or cycloalk (en / in) il; 4) Reduction of the double bond in an indole compound of the following formula VI: where R2-Rs, R1, X, n, m, W, and A are as defined above.

) Reduction of the double bond of tet rahidropiridinil in derivatives of the following formula Vl 1: where R2 R5, Y, n, m, W and A are as defined above; 6) Reaction of a dihydroindole derivative of the formula VIII: where R2-R5, X, A, n, m, W and the dotted line are as defined above, with a reagent of the formula Rx-L, where L is a leaving group such as halogen, mesylate or tosylate and R1 is, as previously defined, or of the formula R "hal or R '-OCOR, in which the formulas hal is halogen, R1 is acyl, thioacyl, a group R1S VCO-, or a group R16 R17 NCO- or R16R17 NCS- where R15, V, R16 and R17 are as defined above, except that neither R16 nor R17 can be hydrogen, or with a lower alkylsulfonyl halide, trifluoride trifluoride halogenide or an isocyanate or trioisocyanate of the formula R16-N = C = 0 or R16- N = C = S, where R16 is as defined above, 7) Reaction of an anilino derivative of formula IX: where one of R2 R5, is NHR14 and R14, is defined above and the other R2-R5, X, Y, A, n, m, W and the dotted line are as defined above, with a reagent of the formula R13"L, where L is a leaving group, such as halogen, mesylate, or tosylate and R13, is as defined above, or of the formula Rn" hal R: OCOR in which formulas hal is halogen, RJ is thioacyl acyl, a group Rlb VCO- or a group R 1Í6O TR, 1"7 'NCO- or R? S Ri7 NCS. (Where R15, V, R16 and RX7, are as defined above, except that neither R16 nor Rx7 can be hydrogen, or with a halogenide of lower isulfonyl, trifluoromethylsulfonium halide or a isocyanate or trioisocyanate of the formula Rld- N = C = 0 or R16- N = C = S, where R16 is as defined above 8) Alkylation of a dihydroindole derivative of the formula X with an alkylation derivative of the Formula XI: where R2- R5, X, Y, A, n, m, W and the dotted line are as defined above, and L is a leaving group, such as as halogen, mesylate, or tosylate, or 9) Reduction of amide carbonyl compounds of the formula XII: where R2 R5, X, Y, A, n, W and the dotted line are as previously defined, and m is 1, 2, 3, 4, or 5; wherein the compound of formula I is separated as free base or as an acid addition salt thereof, pharmaceutically acceptable. The reaction of Methods 6) and 7) are conveniently performed at low temperature (e.g., below room temperature) in an inert solvent, such as a. acetone, dichloromethane, tetrahydrofuran, or dimethyl toxin, when reactive carboxylic acid chlorides, isocyanates or iso t iocyanates are used. The formylated amines are prepared from the corresponding amines by reaction in formic acid, with ethers of formic acid, or by reaction with formic acid anhydride prepared in situ. Generally, the reaction temperatures range from 0 ° C to the boiling point of the formyl precursor compounds.

The alkylations, according to Methods 1) and 8) are generally carried out by refluxing in an appropriate solvent, such as acetone, methyl ester or 1-ketone, tetrahydrofuran, dioxane, ethanol or 2-propanol, in the presence of a base, such as potassium carbonate or triethylamine. The reductions of the double bonds, according to Methods 4) and 5), are generally carried out by catalytic hydrogenation at low pressure (<3 atm) in a Parr apparatus or by the use of reducing agents, such as hydrobromic derivatives or of diborane, as produced in situ from NaBH 4 in trifluoroacetic acid in inert solvents, such as tetrahydrofuran, dioxane or diethyl ether. The reductions, according to Methods 2) and 9), are generally carried out by using LiAIH4, AIH3 or diborane in an inert solvent, such as tetrahydrofuran, dioxane or diethyl ether at room temperature or at a slightly elevated temperature. The halogenation, according to Method 3), is generally carried out by the use of chlorine, bromine, or N-c, succinylimimide, N-bromosuccinimide or other halogen molecule precursor, conveniently in the presence of a catalyst, such as Fe ions. 0 a mineral acid. The indole compounds, such as 7-chloro-1H-indole and 6, 7-dic loro-1H-indole were prepared according to the procedure of G. Bartoli et al., Tetrahedron Lett., 1989, 30, 2129-2132. The two piperazinylindole compounds, that is, 4- (piperazin-1-yl) -1 H-indole and 5- (piperazin-1-yl) -1 H-indole are described in the literature, WO 9533743 Al and North American Patent No. 5576319. The synthesis of 3- (piper i din-4-i 1) -1 H-indole and 3- (1, 2,3,6 , - tet rahidrop ir idin-4-i 1) - 1 H-indole, are described in the European Patent Literature No. 465398 Al. The key intermediaries, such as acid 1 - . 1-indanecarboxylic, (V. Asham and WHLinnel J. Chem. Soc. 1954, 4691-4693, Hansen et al., Helv. Chim. Acta 1982, 33, 325-343) and 6-nitro-1-indanecarboxylic acid lico (G. Kirsch and others Just, Ann, Chem. 1976, 10, 1914) were prepared, according to well-known procedures of the literature. The compounds acid (indan-2-yl) acetic, 3- (indan-2-yl) propionic acid, 4- (indan-2-yl) butyric acid, and 2 - (indan-2-yl) ethanol, they have been described in the literature (Y. Tanaka et al., J Med-Chem., 1994, 37, 2071-2078).

Experimental Section The melting points were determined by a Büchi SMP-20 apparatus and are not corrected. The mass spectrum was obtained in a Quattro MS-MS system from VG Biotech., Fisons Instruments. The MS-MS system was connected to a 1050 HP modular HPLC system. A volume of 20-50 μl of the sample (10 μg / ml) dissolved in a mixture of 1% acetic acid in acetonyl / water 1: 1 was dissolved via the autoloader at a flow of 30 μl. / min. in the source of Elect rospray. The spectrum was obtained in two standard sets of operating conditions. One set for information on molecular weight (MH +) (21 eV) and the other set for inducing fragmentation patterns (70 eV). The antecedent was subtracted. The relative intensities of the ions are obtained from the fragmentation pattern. When no intensity is indicated for the Molecular ion (MH +), this ion was only present under the first set of operating conditions. All the ÍH NMR spectra of all new compounds were recorded at 250 MHz in a Bruker AC 250 instrument or at 500 MHz in a Bruker Avance DRX 500. Deuterated chloroform (99.8% D) or dimethyl sulfoxide (99.9%) D) were used as solvents. The TMS was used as a standard internal reference. The chemical values are expressed in ppm values. The following abbreviations are used for the multiplicity of NMR signals: s = simple; d = double, t = triple, q = quadruple, qui = quintuple, h = heptet, dd = double double, dt = double triple, dq = double quad, t t = triple triple, m = multiple. The NMR signals corresponding to acidic protons are generally omitted. The water content in crystalline compounds was determined by Karl Fischer titration. The standard work procedures refer to the extraction with the indicated organic solvent from suitable aqueous solutions, drying of combined organic extracts (MgSO or anhydrous Na2SO4), filtering and evaporating the solvent in vacuo. For the column chromatography silica gel of type Kieselgel 60, 230-400 mesh ASTM was used.

Example 1- lndanilmethanol, the (intermediate) To a suspension of LiAlH4 (4.7 g) in diethyl ether (200 ml) was added dropwise a solution of ACI3 in diethyl ether (200 ml). A solution of 1-indanecarboxylic acid (10 g) was prepared according to the method of Hansen et al. Helv. Cim. , Act 1982 33, 325-343) in anhydrous tetrahydrofuran (200 ml) was added dropwise at a temperature of 10 -15 ° C.

The mixture was finally stirred. at room temperature for 1.5 hours. The excess of AIH3 was destroyed by the addition of concentrated NaOH solution (25 ml) at 0 ° C. The precipitated inorganic salts were filtered and the solvents evaporated in vacuo leaving 6.8 g. of the compound titrated in the form of viscous oil, which was used without further purification. The following compounds of 1 indanylmethanols were prepared in a similar manner: 6-Bromo-1-indanylmethylene. Starting from the reduction of the corresponding ester of methyl 6-bromo-1-indanecarboxylic acid ester, separated as viscous oil, lb-Example 2 6-cyano-1-indanylmethylene-2a. (intermediate To a solution of 6-bromo-1-indanylmethanol (20 g) in N-me t i 1-2-pyrrole idone NMP) (380 ml) was added CuCN (29 g). The mixture was heated to a temperature of 160 ° C, for six hours. After cooling to 80-90 ° C, the mixture was poured into an aqueous solution (500 ml) of NaCN (4 g). After shaking it for 20 minutes, the excess CuCN was filtered. Ethyl acetate (300 ml) was added and the organic phase was separated and worked. The remaining oil was dissolved in diethyl ether (300 ml) and washed with saturated brine (2 x 100 ml.). The organic phase was separated and developed according to the general procedure, leaving 14.6 g. of the crude titled compound 2a as a viscous oil. Column chromatography on silica gel was used (eluent: ethyl acetate / heptane 6: 4). Without subsequent purification.

Use 3 Me tanosul fonate 6 - cyano - 1 - indani lme tanol, 3a (intermediate) To a solution of 6 - cyano - 1 - indani lme tanol 2a (3 g) and triethylamine (2.8 ml) in dichloromethane (50 ml.) A solution of methanesulfonyl chloride (1.5 ml.) In dichloromethane (25 ml.) Was added dropwise at a temperature of 0 ° C. The mixture was stirred at room temperature for one hour.

Then, water (200 ml) was added and the organic phase was subsequently separated and developed, according to the preceding standard procedure. The remaining crystalline product was stirred with diethyl ether and filtered. Yield 2.7 g. P.f. 62-63 ° C. The following methane sulphonates were prepared in a similar manner: Meososulphone of 1-indanylmethanol, 3b. Separated as viscous oil Me tanosul phona to 6-bromo-1-indani Ime tanol, 3c.

Then 4 3 - [1 - (1-indani-1-carbonyl) -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 4a 1-indanecarboxylic acid chloride (4,5 g), prepared as described in International Patent Application No. WO 9533721-A1 in dichloromethane (25 ml), was added dropwise at a temperature of 0-5 ° C to a mixture of 3 - (1, 2, 3,6-tetrahydropyridin-4-yl) -IH-indole (5 g) (see general method for the preparation in Guillaume et al., Eur. J. Med. Chem. 1987, 22, 3343) and triethylamine (3.8. ml) in THF (50 ml). The resulting mixture was stirred overnight at room temperature. The mixture was poured into an aqueous diluted NH40H solution (500 ml) and extracted several times with dichloromethane (4 x 100 ml). The combined organic phases were worked up according to the above general procedure. The chromatography column (eluted with ethyl acetate heptane 70/30) of the crude product allowed the titration of the pure compound 4a, in the form of viscosity oil (4.7 g) which was used without further purification. In a similar manner, the following amides were prepared: 3- [1- (1-indanylcarbonyl) piperidin-4-yl] -1H-indole-4b- separated as an oil. 6-chloro-3- [1- (7-me toxi-1-indanilcarboni 1) -l, 2,3,6-tetrahydropyridin-4-yl] -IH-indole, 4c Of the compound 23a and 6-chloro-3 - (1, 2, 3, 6-tetrahydropyridin-4-yl) -lH-indole 3- [1- (6-methoxy-l-indanylcarbonyl) -1,2,3,6-te-trahydropyridin-4-yl] -lH-indole, 4d From compound 23b and 3- (1, 2,3,6-t) etrahydropyridin-4-yl) -lH-indole. Example 5 3- [1- (1-indanylmethyl) -1,2,3,6-tetrahydropyridin-4-yl] -lH- ± ndol, 5a To a solution of LiAIH . (1.6 g.) In anhydrous THF (100 ml) at a temperature of 0 ° C, a solution of 3- [1- (1-indanylcarboni 1) - (1, 2, 3, 6) was added dropwise. Tetrahydropyridin-yl) -IH-indole 4a (4.7 g) in anhydrous THF (200 ml). The mixture was stirred overnight at room temperature. The excess LiAIH4 was destroyed by carefully adding 10% water in THF. The precipitated inorganic salts were filtered. The solvents were evaporated leaving a crude titled compound (5.2 g). Recrystallization from 2-propanol allowed to obtain 2.8 g. of pure 5a. P.f. 168-170 ° C. XH NMR (CDC13): d 1.85-2.00 (m, ÍH); 2.30-2.45 (m, ÍH); 2.60 (dd, ÍH); 2.60-2.70 (m, 2H); 2.70-300 (m, 5H); 3.30 (broad t, 2H); 3.45 (quin, ÍH); 6.25 (broad t, ÍH); 7.10-7.25 (m, 6H); 7.30-7.40 (m, 2H); 7.90 (d, lH); 8.10 (broad s, ÍH). MS m / z (%) 329 (M +, 2%), 160 (10%, 131 (100%, 91 (19%).) Similarly, the following indanomet i laminas were prepared: fumarate of 3 - [1 - ( 1-indanylme t il) -piperidin-4-yl] -IH-indole, 5b Prepared from compound 4b, Pf 216-218 ° C. XH NMR (DMSO-d6): d 1.70-2.00 (m, 5H), 2.20-2.35 (m, lH), 2.40-2.50 (m, 2H), 2.65 (dd, lH), 2.80-300 (m, 4H) ), 3.20 (broad t, 2 H), 3.45 (quin, lH), 6.60 (s, 2H), 6.95 (t, lH), 7.05 (t, lH), 7 15-7.30 (m, 4 H), 7.30-7.40 (m, 2H), 7.60 (d, 1H), 10.80 (S, 1H), MS m / z (% ) 331 (M +, 15%), 214 (18%, 131 (100%) 6-chloro-3- [1- (7-metho-l-indan-1-yl) methyl-1,2,3, 6-tetrahydropyridin-4-yl] -lH-indole, 5c Prepared from compound 4c, MP 177-178 ° C. XH NMR (CDCl 3): d 2.15-2.30 (t, 1H); , 55 (s broad, 2H, 2.65-2.70 (m, HH), 2.75-2.90 (m, 2H), 2.90-3.00 (m, HH), 3.25 (d, lH), 3.40 (d, lH), 3.60-3.65 (m, lH), 3.85 (s, 3H), 6.20 (broad s, IH), 6.70 (d, lH), 7.05-7.20 (m, 3H), 7.30 (s, lH), 7.80 (d, lH), 8.25 (s broad, ÍH) .MS m / z (%) 393 (M +), 190 (25%), 161 (100%). Oxalate of 3 - [1 - (6-methoxydandan-1-yl) me t il-1, 2,3,6-tetrahydropyridin-4-yl] -lH-indole, 5d. Prepared from compound 4d. P.f. 118-120 ° C. X H NMR (DMS0-d 6): d 1.90-2.00 (m, 1 H); 2.35-2.45 (m, lH, 2.70-2.95 (m, 4H), 3.15 (t, lH), 3.45 (broad t, s, 2H), 3.50- 3.65 (m, 2H), 3.50-3.65 (-m, 2H) 3.75-3.65 (m, 2H), 3.75 (s, 3H), 3.95 (s broad) , 2H) 6.20 (broad s, ÍH), 6.75 (d, ÍH), 6.95 (s, ÍH) 7.10 (t, ÍH), 7.10-7.20 (m, 2 H), 7.45 (d, lH), 7.55 (s, lH), 7.85 (d, lH), 11.35 / s broad, (H). MS m / z (%) 359 (M +, 6%), 190 (15%) 161 (100%), 147 (74%) Example 6 6-sloro-3- [1- (6-cyano-l-indanylmethyl) -1,2,3,6-te-trahydropyridin-4-yl] -IH-indole, 6a A methane sulfonate mixture of 6 -cyano-l-indanylmet anol, 3a, (1.3 g.), 6-chloro-3 - (1, 2, 3, 6-tetrahydropyridin-4-yl) -IH-indole (2.5 g.) and potassium carbonate (1.9 g.) in NMP (50 ml), was heated for 5 hours at 110 ° C. After cooling the mixture to room temperature, it was poured into water (500 ml) and added ethyl acetate (100 ml.) Worked up according to the preceding general procedure, obtaining 4.7 g of impure product Column chromatography (eluted with ethyl acetate / hept anus / e tanol / triethyl amine 307 60 / 10/4), obtaining 1.5 g of pure compound The crystalline product was stirred with diethyl ether and subsequently filtered, Mp 175-177 ° C. XH NMR (CDC13): d 1.85-2.00 (m, ÍH); 2.35-2.45 (m, ÍH; 2.50-3.00 (m, 8H); 3.30 (broad t, 2H); 3.45 (quin, ÍH); 6.15 (broad t, ÍH); 7.05 (dd, 1 H) 7.20-7.50 (m, 4H); 7.70-7.85 (m 2H); 10.60 (broad s, HI) MS m / z (%) 388 (M +, 4%), 185 (40%), 156 (100%), 129 (53%). In a similar manner, the following indanomet i lamines were prepared: 6-chloro-3 - [1 - (6-cyano-1-indanylmethyl) -piperidin-4-yl] -lH-indole hemifumarate, 6b.

Prepared from compound 3a. P. f .175 - 177 ° C.

XH NMR (DMSO-d, 1.65-2.00 (m, 5H) 2.20-2.30 (m, 3H); 2.40-2.50 (m, 2H); 2.65 (dd, lH); 2.70-3.15 (m, 4H); 3.45 (qui, lH); 6.60 (s, lH); 6.95 (dd, 1H); 7.15 (d, lH); 7.35 (d, 1); 7.45 (d, 1H); 7.55-7.65 (m, 2H); 7.80 (s, lH); 10.95 (s, lH) .MS m / z (%) 392 (M +, 17%), 390 (M +, 47%), 239 (100%), 156 (69%). 6-chloro-3- [1- (4-ce ti lamino-1-indani lme t i 1) -1, 2, 3, 6-tetrahydropyridin-4-yl] -IH-indole, 6c. P.f. 189-190 ° C LH NMR (DMSO-dg): d 1.65-1.90 (m, 1H); 2.05 (s, 3H); 2.10-2.30 (m, 1H); 2.40-2.95 (m, 8H); 3.20 (broad s, 2H); 3.45 (quin, ÍH); 6.15 (broad t, ÍH); 7.00-7.15 (m, 3H); 7.40-7.50 (m, 3H); 7.85 (d, 1H); 9.25 (s, lH); 11.25 (s, lH) .MS m / z (%) 420 (MH +, 16%), 420 (MH +, 16%), 217 (65%), 188 (100%), 146 (57%). The last mentioned compound was prepared from meososulfonate 4-acetylamino-1-indanomet anol, which was obtained again from 4-amino-1-indanomet anol as follows: 4-amino-1 - indanomethanol A mixture of 4-nitro-l-indanecarboxylic acid and 6-nitro-l-indanecarboxylic acid was obtained, according to the procedure to arrive at the nitration of 1-indanecarboxylic acid made by G. Kirsch and others, just. Lieb. Ann. Chem., 1976, 10, 1914. This mixture was reduced with alane, according to the method in Example 1). A mixture (21.9 g) of 4-nitro- and 6-nitroquinoline-1-methanol was dissolved in glacial acetic acid (600 ml) and 5% Pd was added to carbon black (11 g). .). The mixture was hydrogenated in a Parr apparatus under 2 hours for 2.5 hours. The catalyst was filtered and the solvent evaporated in vacuo. Water (500 ml) and ethyl acetate were added (200 ml.) Which were kept at 0 ° C. The pH was adjusted to > 10 by adding aqueous NaOH solution. The organic phase was separated and worked, according to the general procedure above. The shallow inoles 4-and 6- were separated by column chromatography on silica gel (eluted with ethyl acetate / heptane 60/40). The yield of 4-amino-1-indanomet anol as a viscous oil was 3.6 g. 4-Acetylamino-1-indanome tannol methanesulfonate A mixture of 4-amino-indanome tannol (3.4 g) and triethylamine (8.1 ml) in dichloromethane (150 ml:) was added dropwise at a temperature 30 ° C, acetochloride (1.4 ml.) in dichloromethane (20 ml.). The mixture was stirred for an additional hour, while the temperature was raised to 0 ° C. A solution of meosulfonyl chloride (1.7 ml) in dichloromethane (20 ml.) Was slowly added at a temperature below 0 ° C. Finally, the mixture was heated to room temperature. Water (200 ml) and dichloromethane (50 ml) were added. The organic phase was evaporated and worked up, giving a yield of the metronome phona t titrated in the form of oil (6.7 g of the crude product). 6-chloro-3 - [1 - (5-ce t -ylamino-1-indanylmethyl) -1,2,3,6-tetrahydro-pyridin-4-y1] -1H-indole hemifumarate, 6d. P.f. 241 - 242 ° C. XH NMR (DMSO-d6): d 1.70-1.90 (1H, m); 2.00 (3H, s); 2.11-2.30 (1H, m); 2.40-2.60 (2H, m); 2.60-2.95 (5H, m) 3.20 (2H, bs); 3, 25 -3, 40 (2H, m); 6.10 (ÍH, s); 7.05 (ÍH, d); 7.25 (2H, s); 7.40 (ÍH, s); 7.45 (1H, d); 7.55 (1H, s); 7.85 (2, d); 9.80 (1H, bs); 11, 25 (1H, bs) .MS m / z (%) 420 (MH +, 5%), 188 (100%), 146 (100%), 217 (31%), 147 (27%). The last mentioned compound was prepared from 5-acetylamino-1-indanomet anol meosulphonate, which was obtained again from 6-chloro-5-n-t-indanecarboxylic acid.

(G. Kirsch et al., Just, Lieb. Ann. Chem., 1976, , 1914) in a similar manner according to the synthesis described above of methane sulfonate of 4-acetylamino-1-indomethanol. 6-chloro-3- [1- (6-bromo-1-indanylmethyl) -1, 2, 3, 6-t e trahydropyr idin-4-i 1] - ÍH-indole, 6e. The compound was prepared from compound 3c. P.f. 153-155 ° C.

XH NMR (CDC13): d 1.85-1.95 (m, ÍH); 2.30-240 (m, ÍH); 1.65-1.70 (m, 2H); 2.50-2.65 (m, 3H); 2.65-2.90 (M, 5H); 3.25 (broad s, 2H); 3.45 (p, 1 H); 6.20 (broad s, ÍH); 7.00-7.20 (m, 3 H); 7.25 (s, ÍH); 7.30 (d, 1 HOUR ); 7.50 (S, 1H); 7.80 (d, 1H); 8.15 (s broad, ÍH). MS m / z (%) 43 (MH +, 7%), 441 (MH +, 7%), 240 (50%), 238 (49%), 211 (59%), 209 (62%), 130 (100%) Example 7. 6-Chloro-3- [1- [2- (indane-1-yl) methy1carbonyl] -1,2,3,6-te-trahydropyridin-4-yl] -IH-indole, 7a A solution of indane-1-acetic acid was refluxed for four hours (Anderson, AG et al., J. Org. Chem., 1989, 38 (8), 1439-1444) (7.0 g. mmol.), DMF (3 ml.) and SOCI2 (17.5 g., 147 mmol) in CH2C12 (250 ml.). The mixture was evaporated and re-evaporated from toluene to give the corresponding acid chloride. To a solution of 6-chloro-3- (1,2,3,6-tetrahydropyridin-4-yl] -lH-indole (European Patent No. 465398-A1) (9.2 g., 39.7 mmol. ) and TEA (10 ml.) in THF (120 ml), a solution of the acid chloride in THF (120 ml.) was added dropwise over 20 minutes.The mixture was stirred for 1.5 h and evaporated. H20 (50 ml.) was added to the residue and the mixture was extracted with CH2 Cl2 (2 x 150 ml.) After washing with H20 (20 ml) and brine. (20 ml.), The combined organic phases were dried (MgSO.sub.4) and evaporated. The product was purified by column chromatography (EtOAc: heptane = 1: 1) to give the title compound 7a (7.8 g, 50%): XH NMR (DMSO-d6): d 1.55-1, 72 (ÍH, m); 2.20-2.60 (3H, m); 2.69-2.95 (4H, m); 3.48-3.58 (1H, m); 3.61-3.81 (2H, m); 4.18 (2H, bs); 6.12 (ÍH, d); 7.05 (ÍH, dd); 7.08-7.16 (2H, m); 7.17-7.31 (2H, m); 7.42 (ÍH, d); 7.49 (1H, dd); 7.81 (lH, dd); 11.31 (ÍH, bs).

For example, 8-chloro-3- [1- [2- (indan-1-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 8a. LiAIH4 (2.3 g, 60.0 mmol) in anhydrous THF (150 ml), a solution of 6-chloro-3 - [1- (2-indan-1-yl) was added dropwise over 20 minutes. -methylcarbonyl] (1,2,3,6-tetrahydropyridin-4-yl) -lH-indole 7a (7.8 g, 20.0 mmol) in anhydrous THF (150 ml). The mixture was refluxed for 1.5 h. and then cooled to 10-15 ° C. After the dropwise addition of H20 (3 ml), aqueous NaOH (3 ml) (15%) and H20 (12 ml), the solution was filtered and evaporated to dryness. The remainder was dissolved in CH2C12 and after drying with (MgSO4), the solution was evaporated to give the titled compound 8a (5.7 g, 77%). P.f. 181-183 ° C. X H NMR (DMSO-d 6): d 1.45-1.70 (2H m); 1.95-2.15 (1H m); 2.20-2.35 (1H, m); 2.45-2.60 (4H, m); 2.60-2.95 (4H, m); 3.00-3.20 (3H, m); 6.10-6.15 (ÍH, m); 7.00 (ÍH, dd); 7.10-7.25 (4H, m); 7.40 (2H, m); 7.80 (ÍH, d); 11.25 (ÍH, bs). MS m / z (%) 377 (MH +, 38%), 131 (100%). The following compounds were prepared analogously according to the procedures described in Examples 7 and 8.

-Fluoro-3- [1- [2- (indane-1-yl) ethyl] -1,2,3,6-tetrahydro-tetrahydro-4-yl] -IH-indole, 8b. P.f. 172-176 ° C. XH NMR (CDC13): d 1.70-1.80 (m, 2H); 2.30-240 (m, ÍH); 2.60-2.70 (m, 4H); 2.75-2.85 (m, 2H); 2.85-2.90 (m, ÍH); 2.90 (m, ÍH); 2.90-3.00 (m, ÍH); 3.20-3.30 (m, 3H); 6.10 (broad s, ÍH); 6.95 (t, ÍH); 7.15-7.30 (m, 6H); 7.50 (d, ÍH) 8.15 (broad s, HI) .MS m / z (%): 361 (MH +, 67%), 174 (74%), 131 (100%). By hydrogenation of compound 8b at 3 atm in acetic acid using Pt02 as catalyst in a Parr apparatus, oxalate of 5-f luor-3 - [1 - [2- (indan-1-yl) ethyl] -piperidin-4 was obtained -yl] -lH-indole, 8c.

P.f. 107-115 ° C. XH NMR (DMS0-ds) d, 1.55-1.85 (m, 2H); 1.90-2.00 (m, 2H); 2.10 (broad d, 2H); 2.20-2.30 (m, 2H); 2.75-2.85 (m, ÍH); 2.85-2.95 (m, 1 H); 3.00-3.20 (m, 6H); 3.55 (broad s, ÍH), 6.90 (t, 1 H); 7.15-7.20 (m, 2 H); 7.20-7.25 (m, 1 H); 7.30-7.40 (m, ÍH); 7.35 (d, ÍH); 11.00 (s, 1H) MS m / z (%): 363 (MH +, 9%), 117 (10%), 98 (100%). 5-Fluoro-3- [1- [4- (indan-1-yl) bu tan -1-yl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 8 d. 172-176 ° C. XH NMR (CDC13): d 1.40-1.70 (m, 6H); 1.85-1.95 (m, ÍH); 2.25-2.35 (m, ÍH); 2.50 (t, 2H); 2.60 (broad s, 2H); 2.70 (t, 2H); 2.80-2.90 (m, ÍH); 2.90-3.00 (m, ÍH); 3.05-3.15 (m, ÍH); 3.25 (broad s, 2H); 6.10 (broad s, ÍH); 6.95 (t, ÍH); 7.10-7.30 (m, 6H); 7.50 (d, ÍH); 8.10 (s, 1H) .MS m / z (%): 389 (MH +, 9%), 202 (100%), 171 (44%), 129 (73%). By hydrogenation of compound 8d at 3 atm in acetic acid using Pt02 as catalyst in a Parr apparatus, 5-f luor- 3 - [1 - [4 - (indan-1 -yl) butan-1-yl] -piperidin was obtained. - 4 - il] - ÍH- indole, 8e. P.f. 83-86 ° C. XH NMR (CDC13) d, 1.25-1.90 (m, 9H); 1.95-2.10 (m, 4H); 2.20-2.30 (m, HI); 2.35-2.45 (m, 2 H); 2.70-2.90 (m, 3H); 3.05-3.15 (m, 3H); 6.90 (t, 1 H); 6.95 (s, ÍH); 7.10-7.30 (m, 6H); 8.15 (s, 1H) .MS m / z (%): 391 (MH +, 61%), 256 (78%), 98 (100%). 6-chloro-3- [1- [4- (indan-1-yl) butan-1-yl] -piperidin-4-yl] -lH-indole oxalate, 8f. P.f. 206-208 ° C. XH NMR (DMS0-d6) d, 1.40-1.50 (m, 3H); 1.60-1.65 (m, 1H); 1.60-1.65 (m, 1 H); i, 65-1, 70 (m, 2H); 1.80-1.90 (m, ÍH); 1.95-2.10 (m, 4H); 2.20-2.30 (m, 1H); 2.70-2.80 (m, 1H); 2.80-2.90 (m, ÍH); 2.95-3.10 (m, 6H); 3.55 (broad d, 2H); 6.95 (d, ÍH); 7.10-7.30 (m, 5H), 7.40 (s, 1H); 7.65 (d, ÍH); 11.10 (s, 1H) .MS m / z (%): 407 (MH +, 69%), 256 (100%), 117 (39%), 98 (51%). 6-chloro-3- [1- [3- (indan-1-yl) propan-1-yl-] -1,2,3,6-tetrahydropyridin-4-yl] -IH-indole, 8g. P.f. 198-200 ° C. X H NMR (CHCl 3) d, 1.40-1.55 (H, m); 1.60-1.80 (3H, m); 1.75-1.95 (1H, m); 2.20-2.40 (1H m); 2.45- 2.60 (4H, m); 2.70 (2H, t); 2.80-3.00 (2H, m); 3.10- 3.15 (1H, m); 3.20-3.15 (1H, m); 3.20-3.25 (2H, m); 6.15 (ÍH, s); 6.15 (ÍH, s); 7.05-7.30 (6H, m), 7.30 (1H, d); 7.80 (ÍH, d); 8.25 (ÍH, bs) .MS m / z (%): 391 (MH +, 5%), 157 (100%), 129 (76%), 188 (56%). 6-Chloro-3 - [1 - [4 - (indan-1-yl) butan-1-y1-] - 1, 2, 3, 6-tetrahydropyridin-4-yl] -lH-indole oxalate, 8h . P.f. 191-192 ° C. X H NMR (DMSO-d 6) d 1.40-1.50 (3H, m); 1.60-1.65 (1H, m); 1.70-1.80 (2H, m); 1.80-1.90 (MH); 2.30-2.25 (ÍH, m); 2.25-2.30 (3 H, m); 2.30-2.90 (1H, m); 3.05-3.20 (3H, m); 3.35 (2H, bs); 3.80 (2H, bs); 6.10 (HH, m), 7.10 (HH, s); 7.10 (ÍH, d); 7.10 (2H, m); 7.20 (2H, m); 7.45 (H, s); 7.55 (ÍH, s); 7.80 (1H, d) MS m / z (%): 405 (MH +, 6%), 202 (100%), 129 (54%), 171 (36%). The acid synthesis of 3- (indan-1-yl) propane i co and 4- (indan-1-yl) butyanoic acid is described in A. Mukhopadhyay et al. J. Indian Chem. Soc. 1985 , 62 (9), 690-2.

Example 9 Indan-2-carboxylic acid 9a (Intermediate) A solution of indan-2,2-dicarboxylic acid (17 g., Baeyer and Perkin, Ber, 1884, 17, 122) in NMP (200 ml.) it was heated at 150 ° C for one hour. After cooling the solution to 20 ° C was poured into water (300 ml.) And the concentrated hydrochloric acid was added at pH = 1. Worked conventionally with ether to give the titled product (4.7 g.). P.f. 132-33 ° C (from ether).

Example 10 6-Chloro-3- [1- [(indan-2-yl) carbonyl-] -1,2,3,6-te-trahydropyridin-4-yl] -lH-indole, 10a To a solution of 9a (2.1 g *) in dichloromethane (200 ml.) Was added thionyl chloride (1.4 ml.) And DMF (2 ml.). After refluxing for 2.5 hours, the mixture was concentrated in vacuo and dissolved in DMF (50 ml). The solution was added dropwise to an ice-cooled solution of 6-chloro-3- (1,2,3,6, -tetrahydropyridin-4-yl) -lH-indole (European Patent Publication No. 465398-Al) ( 3.0 g.) In DMF (200 ml) and triethylamine (9 ml.). The reaction mixture was kept under stirring at room temperature for 16 hours and then poured into a saturated solution of sodium chloride (500 ml). . Worked conventionally with ethyl acetate to give the titled product (4.7 g.), Which was sufficiently pure for a subsequent reaction. In a similar manner, the following compounds were prepared: 3- [1- [(indan-2-yl) carbonyl-] -1,2,3,6-te-trahydropyridin-4-yl] -1H-indole, 10b. Prepared from compound 9a and 3- (1, 2,3,6-tetrahydropyridin-4-yl] -lH-indole, 7-chloro-3- [1- [(indan-2-yl) carbonyl-] -1, 2, 3, 6-tetrahydropyridin-4-yl] - 1H-indole, 10c.

Prepared from compound 9a and 7-chloro-3- (1,2,3,6-te-trahydropyridin-4-yl] -l-n-dol., 6,7-dichloro-3- [1- [(indan-2 -yl) carbonyl-] -1,2,3,6-te trahidropir idin-4-yl] - 1J5T-indole, 10 Prepared from compound 9a and 6,7-dichloro-3 - (1, 2, 3,6-tetrahydropyridin-4-yl] -lH-indole, 3- [1- [(indan-2-yl) carbonyl-] -1,2,3,6-te rahydropyridin-4-yl] -5,6- Methylenedioxy-1H-indole, 10e Prepared from compound 9a and 5,6-methylenedioxy-3- (1, 2,3,6-tetrahydropyridin-4-yl) -lH-indole, 5- [4- [( indan-2-yl) carbonyl] -piperazin-1-yl] -1H-indole, lOf Prepared from compound 9a and 5- (piperazinyl) -I, i-indole. 6-Chloro-3- [1- [2- (indan-2-yl) methylcarbonyl-] -1,2,3,6-tetrahydropyrid-4-yl] -1H-indole, 10Og. From 2 - (indan - 2 - i 1) - acetoxy and 6 - chloro - 3 - (1, 2, 3, 6 - tetrahydropyridin - 4 - yl] - lH - indole, 6 - chloro - 3- [ 1- [3- (indane-2-yl) ethylcarbonyl] -1,2,3,6-te-trahydropyr id-4-i 1] -IH-indole, lOh. From 3 - (indan-2- il) propionic and 6-chloro-3-1, 2, 3, 6 -tetrahydropyr idin4-i 1] - 1H-6-chloro-3- [1- [4- (indan-2-yl) propylcarbonyl- ] -1, 2, 3, 6-tetrahydropyrid-4-yl] -1 H-indole, lOi From 4 - (indan-2-yl) butyl and 6-chloro-3- (1, 2, 3, 6-tetrahydropyridin-4-yl] -lH-indole.

The oxalate of 6-chloro-3 - [1 - (indan-2-yl) me ti-1, 2, 3, 6-tetrahydropyridin-4-yl] -IH-indole, a solution of 10a ( 3.2 g.) In anhydrous THF (100 ml.) Was added to a cooled suspension of LiAlH4 (0.9 g.) In THF (150 ml) at a temperature of 5 ° C. The mixture was stirred at room temperature for 4 hours. The mixture was then cooled on ice and after the addition of water (1.5 ml) by dropping, 15% NaOH (1 ml) and water (3.5 ml), said mixture was filtered and evaporated in vacuo. The residue was dissolved in CH2C12 and developed in a conventional manner giving a yield of yellow crystals (3.2 g.), Which were recrystallized from acetone, giving 1.1 g. , p.f. 161-63 ° C. The titrated oxalate was crystallized from acetone, yield 0.45 P. f 203 -5 ° C LH NMR (DMSO-dg) d 2.65-2.80 (m, ÍH); 2.95-3.30 (m, 5H); 3.65 (s, 2H); 6.15 (s, ÍH); 7.05 (dd, ÍH); 7.10-7.15 (m, 2H); 7.15-7.25 (m 2 H); 7.45 (d, ÍH); 7.55 (d, ÍH); 7.85 (d, ÍH); 11.45 (s, ÍH). MS m / z (%) 363 (MH +, 1005%), 245 (17%, 230 (20%). Similarly, the following compounds were prepared: 3- [1- (indan-2-yl) methyl-1 2,3,6-tetrahydropyridin-4-yl] -IH-indole, 11 b.Prepared from 10b, Pf 156-157 ° C. XH NMR (DMSO-ds) d 2.40-2.85 ( m, 7H), 2.90-3.10 (m, 2 H), 3.15 (d, 2 H), 6.15 (s, 1 H), 6.95-7.25 (m, 6) H), 7.30-7.40 (m 2 H), 7.80 (d, 1 H), 11.10 (s, HI), MS m / z (%) 329 (MH +, 84%), 160 (87%), 131 (100%). Oxalate of 7-c parrot-3 - [1 - [(inda-2-i 1) me ti 1 -] - 1, 2,3,6-tetrahydropyridin-4 -yl] -lH-indole, 11c.

Prepared from 10c. P.f. 135-136 ° C. XH NMR (DMSO-dg) d 2.70-3.05 (m, 5H); 3.05-3.20 (m, 2H); 3.30 (d, 2 H); 3.40 (t, 2 H); 3.90 (s, 2 H); 6.20 (s H); 7.05-7.30 (m, 6H); 7.60 (d, ÍH) 7.85 (d, ÍH): 11; 75 (s, ÍH) .MS m / z (%) 365, 363 (MH + 46%, 81%), 160 (100%) , 131 (53%), 98 (81%). 6,7-dichloro-3- [1- [(indan-2-yl) methyl] -1,2,3,6-te-trahydropyridin-4-yl] -IH-indole, lid. Prepared from lOd. P.f. 151-152 ° C. * H NMR (CDC13) d 2.45-2.65 (m, 4 H); 2.65-2.90 (m, 5 H); 3.00-3.20 (m, 2 H); 3.20-3.30 (m 2H); 6.15 (s broad, ÍH); 3.20-3.30 (m, 2H), 6.15 (broad s, ÍH); 7.05-7.30 (m., 6H); 7.70 (d, ÍH); 8.35 (broad s, HI) .399, 397 (MH + 33%, 53%), 160 (100%), 131 (24%). 3- [1- [(indan-2-yl) methyl-] -1,2,3,6-tetrahydropyridin-4-yl] -1H-indole, lie. Prepared from lOe. P.f. 192-193 ° C. XH NMR (DMSO-d6) d 2.40 (d, 2 H); 2.55-2.80 (m, 5 H); 2.95-3.05 (m, 2 H); 3.15 (s, 2 H); 5.95 (s 2H); 6.00 (s, ÍH); 6.90 (s, ÍH), 7.05-7.15 (m, 2H): 7.15-7.20 (m, 3H); 7.25 (s, ÍH); 11.90 (s 1H) .MS m / z (%) 373 (MH + 100%), 160 (100%), 131 (73%), 114 (80%) 5 - [4 - [(indan-2-y1) e-t-yl-piperazin-1-yl] -lH-indole dihydrochloride, llf. Prepared from lOf. P.f. 263-265 ° C.xH NMR (DMSO-d6) d 2.80-2.90 (m, 2H) 2.90- 3.05 (m, 1 H); 3.05-3.25 (m, 2 H); 3.40 (d, 2H) 3.45-3.95 (m, 8H); 6.45 (s, ÍH); 7.05-7.25 (m, 5H) 7.35-7.65 (m, 3H); 11.25 (s, ÍH); . MS m / z (%) 332 (MH + 31%), 159 (100%), 131 (72%). 6-Chloro-3- [1- [2- (indan-2-yl) ethyl-] -1,2,3,6-t-e trahydropyridin-4-yl] -IH-indole, IIg Prepared from lOg. P.f. 217-218 ° C. X H NMR (DMSO-d 6) d 1.70 (q, 2 H); 2.35-2.70 (m, 9H); 2.90-, 20 (m, 4 H); 6.10 (broad s); 6.95-7.25 (m 5H); 7.40 (d, 2H), 7.80 (d, ÍH); 11.25 (broad s, 1H). MS m / z (%) 379, 377 (MH + 7%, 16%), 174 (93%), 143 (100%). 6-Chloro-3- [1- [3- (indan-2-yl) propan-l-yl] -1,2,3,6-te-trahydropyridin-4-yl] -IH-indole, 11 h. Prepared from lOh. P.f. 176-177 ° C. X H NMR (DMSO-d 6) d 140-1.70 (m, 4 H); 2.30-2.70 (m, 9H); 2.90-3.15 (m, 4H); 6.10 (broad s); 6.95-7.25 (m, 5H); 7.40 (d, 2H), 7.80 (d, ÍH); 11.25 (broad s, HI) 391 (MH + 6%), 188 (100%), 129 (47%). 6-chloro-3- [1- [4- (indan-2-yl) butan-1-yl-] -1,2,3,6-te trahydrop-id id-4-y1] -lH-indole, lli Prepared from 101. P.f. 211-214 ° C. XH NMR (DMSO-d d 1.30-1.65 (m, 6H); 2.25-2.70 (m, 9H); 2.90-3.15 (m, 4H); 6.10 (m. s broad), 6.95-7.25 (m 5H), 7.40 (d, 2H, 7.80 (d, 1H), 11.25 (s broad, 1H), 407, 405 (MH + 4 %, 10%), 202 (100%), 129 (93%). With compound 40a as starting material following the procedures of exam 10 and 11, the following compound was prepared: 6-chloro-3-oxalate [ 1 - [(4 - (2-propyl) oxy indan-2-yl) ethyl] -piperidin-4-yl] -IH-indole, llh, Pf 119-126 ° C LH NMR (DMSO-d6) d 1, 26 (3H, d); 1.27 (3H, d); 1.95-2.2 (4H m); 2.60 (1H, dd); 2.74 (ÍH, dd); 2.91 (1H, quin), 3.0-3.2 (5H, m); 3.2-3.3 (2H, m); 4.57 (ÍH, h); 6.77 (2H, t), 7.0 (1H, dd); 7.09 (H, t); 7.20 (H, s); 7.41 (H, s); 7.66 (1H, d) .MS m / z (%): 423 (MH + 59%), 249 (21%), 147 (20%) 98 (100%).

It employed 12 -me i 1 -1-indanon-3-carboxylic acid, 12a (Intermediate) to a mixture of o-1-olualdehyde (500 g), ethyl cyanoacetate (445 g) and ethanol (500 ml) piperidine (16 ml) was added. After azeotropic distillation (200 ml) more ethanol (200 ml) was added, and the mixture was refluxed for two hours. The solution was cooled to 40 ° C and a solution of NaCN (225 g.) In water (300 ml) was added for 20 minutes. The mixture was stirred for one hour and then left for 16 hours at room temperature. The concentrated HCl (5 1) was added slowly and then water / ethanol was distilled until the temperature reached 100 ° C. The mixture was then refluxed for 4 hours and then stirred at room temperature for 16 hours. The mixture was filtered, and the crystals washed with water. The crystals were dissolved in 4 M NaOH (3 1) and filtered. Then the pH was adjusted to 1 with concentrated hydrochloric acid, and the crystals were filtered and dried giving a yield of 610 g. , which was dissolved in thionyl chloride (2 1). DMF (10 1) was added and the solution was refluxed for 2.5 hours and evaporated in vacuo. The residue was dissolved in CH 2 Cl 2 (1.2 1) and added for one hour to a mixture cooled with A1C13 (600 g) in CH 2 Cl 2 at 0-5 ° C. The mixture was stirred at room temperature for 16 hours and then poured into ice / water (5 1) and concentrated hydrochloric acid (500 ml.). Then the titled crude product (605 g.) Was obtained, which was purified by column chromatography on silica gel, eluted with CH2Cl2-acetic acid-ether (50: 50: 2), giving 236 g. of the titled product.

Use of 7-methyl-1-indan-1-carboxylic acid, 13a (Intermediate) To a solution of 12a (100 g.) In triethylhydroacetic acid is added triethyl (141 g.). The mixture was stirred for 72 hours at room temperature and then evaporated in vacuo; the residue was dissolved in ethyl acetate and extracted with dilute NaOH solution. The aqueous phase was washed with ethyl acetate and then acidified with concentrated hydrochloric acid. Conventional absorption with ethyl acetate gave 80.4 g. of raw product. Purification on silica gel eluted with ethyl acetate-heptane anoacetic acid, which gave the titled compound (76.6 g.).

Use of acid, 3, 6, 7, 8-tetrahydrocyclopen [e] indole-8-carboxylic acid, 14a (intermediate) A solution of 13a (61.2 g.) In CH2Cl2 (100 ml.) Was added with stirring for 20 minutes. minutes at 50 ° C, to a mixture of concentrated nitric acid (150 ml.) and CH2Cl2 (40 ml.). After stirring at -52 ° C for 30 minutes, the mixture was poured onto ice and saturated with NaCl solution. Conventional absorption with ethyl acetate gave 58.2 g. of the crude product, which was purified on silica gel eluted with hept ano-ethyl acetate (2: 1) to give 45.6 g. of the product, containing 32% of the 5-nitro compound together with other nitro compounds. This product was dissolved in DMF (200 ml.) And heated to 88 ° C. T r - (dimet i lamino (metal (34.5 g)) was added and the temperature was raised to 123 ° C and the mixture was stirred for two hours, the mixture was cooled to 27 ° C and a semicarbac solution was added. One hour, HCl (19 g.) in water (200 ml) was added for 8 minutes.The mixture was then stirred for 70 minutes at room temperature Ethanol (500 ml) and iron powder (30 g.) and acid were added. acetic acid (120 ml) in portions at 50 ° C. After refluxing for 45 minutes, the mixture was filtered and concentrated to 500 ml in vacuo, water was added and the mixture was taken up in ethyl acetate. of silica, eluted with ethyl acetate, giving 5.7 g of the titled product, Pfl66-7 ° C.

Example 15 8- [4- (6-Chloro-1H-indol-3-yl) -1,2,3,6-tetrahydropyridin-4-yl-carbonyl] -3,6,7,8-heptohydrocyclope [ e] indole, 15a A solution of 14a (1,4 g.) 6-chloro-3- (1,2,3,6-tetrahydropyridin-4-yl) -1-H-indole (1, 6g.), di c iclohexylcarbodi imide (1.9 g *) and 4-dimethylaminopyridine (0.1 g.) in THF (100 ml.) was stirred for 24 hours at room temperature. The mixture was filtered and evaporated in vacuo. The residue was purified on silica gel eluted with ethyl acetate-heptane (3: 2), giving 1.1 g. of the product titled as amorphous powder.

EXAMPLE 16 8- [4 - (6-Chloro-1H-indol-3-y1) -1,2,6,6 -te-rahydropyridin-4-ylmethyl] -3,6,7,8-tetrahydrocyclopentyl oxalate e] indole, 16a. The titled product was prepared from 15a (1.05 g.), As described in Example 3, Yield 0.59 g. Mp. 155-7 ° C. XH NMR (DMS0-d6) d 210. 2.40 (m, 2H); 2.57-2.95 (m 3H); 2.95-3.25 (m, 2 H); 3.35-3.65 (m, 3 H); 3.85-4.10 (m, 3 H); 6.15 (s, ÍH); 6.50 (s, ÍH); 6.95 (d, 1H), 7.10 (dd, ÍH); 7.25 (d, 1 H); 7.35 (t, 1H); 7.45 (d, 1 H); 7.55 (d, ÍH); 7.85 (d, ÍH); 11.15 (s, ÍH); 11.55 (s, ÍH) MS m / z (%): 402 (MH + 6%), 170 (96%), 156 (100%).

Example 17 4-n-troindan-2-carboxylic acid chloride, 17a (Intermediate) A mixture of 3 - nor t - or - x log was heated (100 g), N-bromosuccinimide, and dibenzoyl peroxide (2 g) to reflux for 14 hours. The mixture was filtered and evaporated in vacuo to give an oil (202 g), which was purified on silica gel eluted with heptane-ether (10: 1) giving 86.4 of a bromine compound, which was dissolved in NMP (850 ml) and added to a mixture of diethyl malonate (38 g.) And 30% Na -me t anolat or in methanol (105 ml) in NMP (11) at 53-60 ° C. After stirring for 30 minutes at 60 ° C, the mixture was cooled, poured into cold water, and prepared with a mixture of ether and ethyl acetate. The residue was purified on silica gel, eluted with toluene-ethyl acetate (6: 1). The product (25.1 g.) Was dissolved in ethanol (250 ml) and THF (50 ml.) KOH (27 g.) In water (150 ml.) Was added and the mixture was stirred for 16 hours at room temperature. . The mixture was concentrated in vacuo to 100 ml. and it was filtered through activated carbon. The filtrate was acidified with concentrated hydrochloric acid and was absorbed with a mixture of ether and ethyl acetate. The residue was dissolved in NMP (150 ml) and heated at 145 ° C for 10 minutes. The solution was cooled to room temperature and poured into a saturated solution of NaCl. It was developed with ether / ethyl acetate in a usual manner, yielding 10.7 g. of a solid, of which 6.0 g. were dissolved in CH2C12 (100 ml.) and DMF (1 ml). Thionyl chloride (8.4 ml) was added and the solution was refluxed for 16 hours. Evaporation in vacuo gave the microcrystalline titled compound (8.4 g.) 5-n-troindan-2-carboxylic acid chloride, 17b A solution of indan-2-carboxylic acid 1a-9a (18.8 g.) in ether (250 ml.) was added to concentrated sulfuric acid (300 ml.) (temp. = 3-13 ° C). To this mixture, a concentrated nitric acid solution (4.4 ml.) Was added and concentrated sulfuric acid (100 ml.) (Temp. = -1 ° C) was added. The mixture was stirred at 2-8 ° C for 1 hour, poured on ice, and the aqueous phase was extracted with ether. The combined organic extracts were washed with brine, dried (MgSO 4) and evaporated to dryness in vacuo. The residue was crystallized from ether to give 5-ni troindan-2-carboxylic acid (6.0 g.). The solid was dissolved in CH2C12 (100 ml) and DMF (1 ml). Thionyl chloride (8.4 ml.) Was added and the solution was boiled under reflux for 5 hours. Evaporation in vacuo gave the titled compound (8.6 g.). E xample 18 6-chloro-3 - [1 - (4-acetylaminoindan-2-yl) e t-1, 2, 3, 6-tetrahydro-idin-4-yl] -lH-indole oxalate, 18a To a solution of 6-chloro-3 - (1, 2, 3, 6 -tetrahydropyr idin-4-yl] -IH-indole (6.4 g.) In DMF (250 ml) and triethyl-amine (1 , 4 g.) Was added to a solution of 17a (8.4 g.) In DMF (50 ml), for 25 minutes at 3-5 ° C. The mixture was then stirred for 45 minutes at room temperature at room temperature and then poured into water The precipitate was filtered, washed with water and dried to give 9.11 g of solid product, which was suspended by refluxing in 90% ethanol (450 ml) Iron powder (9 g) was added. .) and concentrated hydrochloric acid (1.8 ml) in portions for 15 minutes, and the mixture was refluxed for an additional hour The mixture was concentrated in vacuo, and ice and concentrated ammonium hydroxide were added. of ethyl, which gave 4.67 g and was treated with LiAIH4, as described in Example 11, giving 3.2 g of solid, of which 2. g were dissolved in THF (50 ml.) and in triethylamine (3.5 ml) To the solution cooled with ice, a solution of acetyl chloride (0.43 g.) In THF (15 ml) was added at 14 ° C. After heating the mixture to room temperature, it was filtered and evaporated in vacuo, and the residue was purified on silica gel with ethyl acetate-triethylamine acetate (100: 4: 4), yielding 1, 51 g. from which the titled product was crystallized as oxalate salt from 2-propanol. Yield 1.29 g. Pf. 143-4 ° C. XH NMR (DMS0-d6) d 2.0 (s, 3H_); 2.55-3.00 (m 5H); 3.00-3.15 (m, 4H); 3.25 (broad s, 2H); 3.70 (s, 2H); 6.15 (s, ÍH); 7.0 (d, ÍH); 7.05-7.15 (m, 2H), 7.35 (d, ÍH); 7.45 (d, 1H); 7.55 (d, ÍH); 7.85 (d, ÍH); 9.40 (s, ÍH); 11.45 (s, HI) MS m / z (%): 420 (MH + 11%), 217 (87%), 174 (100%). In a similar manner, the following compound was prepared: 6-c-loro-3 - [1 - (4-ac e t -lamino indan-2-y1) me t -piperidin-4-yl] -IH-indole oxalate, 18b. From 6-chloro-3 - (piperidin-4-yl) -IH-indole and 17a. Mp. 153-5 ° C. XH NMR (DMS0-d6) d 1.80-2.10 (m, 7H); 2.55-3.15 (m 10H); 3.40 (broad d, 2H); 6.95-7.05 (m, 2H), 7.10 (t, ÍH); 7.20 (d, ÍH); 7.35-7.40 (m, 2 H); 7.60 (d, ÍH); 9.35 (s, ÍH); 11.05 (s, ÍH). MS m / z (%): 422 (MH + 100%), 249 (2%), 98 (16%). The appropriate acids w- (6-acetylamino-1-indanyl) -alkanoic acids were converted to the corresponding acid chloride, as described in Example 17, and the reaction was carried out, as described in Example 18, with 6-chloro-3 - (1, 2, 3, 6 -tetrahydropyr idin-4-yl) -IH-indole to give the following compounds: 6-chloro-3 - [1 - [2 (6-ace) oxalate laminoindan-1-yl) ethyl] -l, 2,3,6-tetrahydropyridin-4-yl] -lH-indole, 18c. Mp. 153-155 ° C. XH NMR (DMSO-d6) d 1.60-1.90 (2H, m); 2.00 (3H, s); 2.10-2.35 (2H, m), 2.65-2.90 (4H, m); 3.05-3.30 (3H, m); 3.30-3.50 (2H, m); 3.90 (2H, bs); 6.10 (ÍH, s); 7.05-7.15 (2H, m); 7.25 (2H, d); 7.45 (H, s); 7.60 (2H, m); 7.85 (HH, d), 9.90 (HH, bs); 11.50 (ÍH, bs). MS m / z (%): 454 (MH + 3%), 188 (100%), 231 (14%), 174 (12%) 6-chloro-3 - [1 - [3 (6- aceylaminoindan-1-yl] ropan-1-yl] -1,2-oxalate, 3,6-tetrahydropyridin-4-yl] -IH-indole, 18d., Pp. 110-115 ° C. XH NMR (DMSO-dg) d 1.35-1.50 (1H, m); , 70 (HH, m), 1.80 (3H, bs), 2.00 (3H, s), 2.20-2.39 (HH, m), 2.65-2.90 (4H, m) ), 3.05-3.20 (3H, s), 3.90 (2H, bs), 3.80 (2H, bs), 6.10 (HI, s), 7.05-7.10 ( 2H, m), 7.25 (2H, d), 7.45 (HH, s), 7.55 (HH, d); 7.80 (ÍH, d); 9.80 (1H, bs); 11.50 (ÍH, bs). MS m / z (%): 448 (MH + 5%), 245 (100%), 214 (35%), 246 (16%) oxalate of 6-chloro-3 - [1 - [4-6-ace ti laminoindan-1 -yl) butan-l-yl] -l, 2,3,6-tetrahydropyridin-4-yl] -1H-indole, 18e. Mp. 125-128 ° C. XH NMR (DMSO-d6) d 1.25-1.50 (3H, m); 1.50-1.90 (4H, m); 2.00 (3H, s); 2.10-2.30 (1H, m); 2.60-2.90 (4H, m); 2.90-3.15 (3H, s); 3.40 (2H, bs); 3.80 (2H, bs); 6.10 (ÍH, s); 7.00 -7.10 (2H, m); 7.25 (ÍH, d); 7.45 (HH, s), 7.55 (HH, d); 7.80 (ÍH, d); 9.85 (ÍH, bs); 11.50 (ÍH, bs). MS m / z (%): 462 (MH + 4%), 186 (43%), 228 (17%). 2- (6-Acetyl-laminoindan-1-yl) acetic acid, 3- (6-acetylaminoindan-1-yl) propanoic acid, and 4- (6-acetylaminoindan-1) acid were prepared. - i 1) but anoic acid, from 6-nitro-1-indanecarboxylic acid, by classical chain praises, using KCN or diethyl malonate. The methodology is described for an analogous indano series by R. Gruber et al., Tetrahedron (Tetrahedro) 1974, 30, 3605-10. Alano was used for the reduction of intermediate carboxylic acids. 3 - [1 - (5-Acetylaminoindan-2-yl) me ti 1 -1,2,3,6-tetrahydropyridin-4-yl] -6-chloro-lH-indole oxalate, 18f. Mp. 201 -203 ° C. XH NMR (DMS0-ds) d 2.00 (s, 3 H); 2.55-3.20 (m 11H); 3.55 (broad s, 2H); 6.15 s broad, 2H); 7.00-7.15 (m 2 H); 7.25 (d, 1 H); 7.45 (d, 1 H); 7.50 (broad s, 2H); 7.85 (d, 1 H); 9.80 (s, 1 H); 11.40 (broad s, ÍH). MS m / z (%): 420 (MH + 5%), 217 (12%), 174 (100%). 3 - [1 - (5-Acetylaminoindan-2-yl) methylpiperidin-4-yl] -6-chloro-1H-indole hemifumerate, 189. Mp. 151-152 ° C. XH NMR (DMSO-d6) d 1.65-2.05 (m, 7H); 2.30 (t, 2 H); 2.45-2.90 (m SH); 2.90-3.20 (m, 4 H); 2.90-3.20 (m, 4H); 6.55 (s, ÍH); 6.95 (dd, ÍH); 7.10 (d, ÍH); 7.15 (d, ÍH); 7.25 (dd, 1H); 7.50 (s, ÍH); 7.60 (d, 1H); 9.80 (s, ÍH); 10.95 (broad s, ÍH). MS m / z (%): 424, 422 (MH + 19%, 54%), 249 (13%), 98 (100%).

EXAMPLE 19 L-Acetyl-2,3-dihydro-3- [2- (ethanesulfonyl) ethyl] -1H-indole, 19a (Intermediate) To a solution of indo 1 -3-acetic acid (100 g.) in methanol (11) ether saturated with HCl (200 ml) was added and the solution was left at room temperature for 3 hours. The solution was evaporated in vacuo and the residue was dissolved in THF 1.2.1) and added slowly by cooling a stirred suspension of LiAlH4 (28.6 g.) In THF (11).

After stirring for 3 hours at room temperature, the mixture was cooled on a low ice and water (57 ml.), Then 15% NaOH (29 ml.) And water (143 ml.) Were added. The mixture was filtered and evaporated in vacuo; the residue (84.9 g.) was dissolved in dioxane (15 1). A complex of boranot rimethylamine (200 g) was added, and hydrochloric acid (150 ml) was added to the stirred mixture for one hour, the mixture was heated at 40 ° C for 30 minutes and then refluxed for 2 hours. After 5 hours, then 6M hydrochloric acid (460 ml) was added and the reflux continued for 30 minutes.The solution was concentrated in vacuo and the residue was poured on ice.The solution was washed with ether and basted with NaOH with centering and then it was extracted with ether, the organic phase was dried (MgSO4) and evaporated in vacuo, the residue was dissolved in CH2Cl2 (680 ml) and triethylamine (68 ml), then acetyl chloride (36 ml) was added 5 ° C, for one hour, after receiving stirring for one hour at room temperature, the mixture was washed with dilute hydrochloric acid and with NaOC03 solution. Then, after drying (MgSO4) and evaporation in vacuo, the residue was dissolved in methanol (500 ml), and 30% Na-methanolat (10 ml) was added. The mixture was stirred for 4 hours at room temperature and then evaporated in vacuo, and was dissolved in CH2C12 and washed with saturated NaCl solution, dried (MgSO4) and evaporated in vacuo. The residue was dissolved in CH2Cl2 (11) and triethylamine (100 ml). Upon cooling, a solution of methanesulfonic chloride (27 m) in CH2C12 (175 ml) was added at 10 ° C. After stirring for 30 minutes at 0 ° C, and one hour at room temperature, the mixture was evaporated in vacuo and purified on silica gel eluted with ethyl acetate. ethyl to give the product titled as oil (74 g.). In a similar manner, the following compounds were prepared: 1- formyl -2,3-dihydro-3- [2- (me tansulfonyl) ethyl] -1H-indole 19b. The formylation was carried out with a mixture of formic acid and acetic acid anhydride. The compound was an oil. l-acetyl-5-bromo-2,3-dihydro-3- [2 - (me tansul foni 1) eti 1] - ÍH-indole 19c. Bromination was performed by treatment of 19a with bromine in a mixture of acetic acid and dichloromethane. The compound was an oil. l-tert-butoxycarbonyl-2,3-dihydro-3- [2- (methanesulfonyl) ethyl] -IH-indole 19d. The ter-butoxic arboni 1 ac ion was made with di-tert-butyl dicarbonate. The compound was an oil. 1-tert -butoxycarbonyl-2,3-dihydro-3 - [4- (methanesulfonyl) butan-1-yl] -IH-indole 19e. From 4 - (1H-indol-3-yl) butyric acid. l-acetyl-5-fluoro-2,3-dihydro-3- (2-bromoet i 1) - 1 H -indole, 19f. 5-F loror-indole (15.0 g., 135.2 mmol.) Was dissolved in anhydrous Et20 (450 ml) and cooled to 0 ° C before adding a solution of oxalyl chloride in anhydrous Et20 (50 ml. ) , during 15 minutes. The mixture was stirred for 30 minutes at 0 ° C and for 3 hours at room temperature. The crystals were collected by filtration and washed with Et20 to give 19.5 g. of solid, which was dissolved in EtOH (140 ml.) and cooled to 0 ° C before adding triethylamine (9.6 g.) per drop. The mixture was refluxed for 3 hours and stirred at room temperature for 24 hours. The crystals were collected by filtration and washed with H20 and Et20 to give 18.0 g. of solid, which after drying in a vacuum oven, was dissolved in anhydrous THF (150 ml) and added dropwise to a cooled suspension (5-15 ° C) of LiAlH4 (16.1 g.) in anhydrous THF ( 350 ml). The mixture was refluxed for 4 hours and cooled to 10 ° C. After the dropwise addition of H20 (16 ml), aqueous NaOH (15%) (16 ml) and H20 (80 ml), the solution was filtered and evaporated almost to dryness. The residue was dissolved in EtOAc and reacted with (MgSO4). Evaporation of the solvent gave the compound 2 - (5-f luor indole-3-i1) and ano 1 (15.2 g.) As oil, which was treated, as described in example 19, beginning with the reduction of boranot rime t lamina, to give the mesylate, which was refluxed for two hours in acetone (200 ml.) cite LiBr (8.0 g.). The mixture was cooled, filtered, evaporated and purified by column chromatography using EtOAc: hept ano = 1: 2 as an eluent to give the titled compound (9.0 g). l-acetyl-5-methyl-2, 3-dihydro-3- (2-bromoethyl) -1H-indole, 19g. Prepared similarly to 19f.

For example, 20 3- [1- [2 (l-acetyl-2, 3-dihydro-1H-indol-3-yl] ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -6-chloro -lH-indole, 20a A mixture of 6-chloro-3- (1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, (1.6 g.), 19a (2.0 g.) Was refluxed for 16 hours. ), K2CO3 (4.0 g) and methyl isobutyl ketone (20 ml) The mixture was filtered and evaporated in vacuo, the residue was purified on silica gel and eluted with ethyl acetate and methanol-triethylamine (90). : 5: 5) Crystallization from ethanol gave the titled product (0.3 g), Mp 1724 ° C. XH NMR (DMSO-d6) d 1.75-1.95 (m, 1H); 2.05-2.20 (m, HH), 2.25 (s, 3H), 2.50-2.65 (m, 4H), 2.75 (t, 2H), 3.25 (broad) , 2H), 3.45-3.60 (m, HH), 3.80 (dd, HH), 4.20 (t, HH), 6.15 (s broad, HH), 7.00-7 15 (m, 3H), 7.25 (m, 1H), 7.45 (d, 2 H), 7.80 (d, 1H), 8.15 (s, lH), 8.25 (d) , HH) MS m / z (%): 420 (MH + 7%), 174 (100%), 144 (55%) In a similar manner the following compounds were prepared: 3- [1- [2 (l -acetyl-2,3-dihydro-lH-indol-3-yl] ethyl] -piperidin-4-yl] -6-chloro-1H-indole, 20b, from 19a and 6-c, parrot-3 - ( p iper idin- 4 - i 1) - ÍH- indole (European Patent Publication No. 465398A-1. Pf.188-90 ° C. XH NMR (DMSO-dg) d 1.70-1.90 (m, 3H); 1.95-2.20 (m, 5H); 2.25 (s, 3 H); 2.40-2.55 (m, 2 H); 2.80 (tt, 1 H); 3.00-3.10 (m, 2 H); 3.40-3.55 (m, ÍH); 3.75 (dd, ÍH); 4.20 (t, ÍH); 6.95 (d, ÍH); 7.05 (ddd, ÍH); 7.25 (dt, lH); 7.35 (d, lH); 7.55 (d, ÍH); 8.00 (S, 1H); 8.25 (d, ÍH). MS m / z (%): 422 (MH + 100%), 249 (15%), 146 (19%). 6-chloro-3- [l- [2 (l-formyl-2, 3-dihydro-1H-indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -IH- indole 20c. From 19b and 6-chloro-3 - (1, 2, 3, 6-tetrahydropyridin-4-ii) -IH-indole. Pf. 183-5 ° C (from acetone). XH NMR (DMSO-d6), the spectrum shows a hidden rotation, which is suppressed by applying heat above 100 ° C d 1.60-1.80 (m, ÍH); 1.95-2.10 (m, HI); 2.35-2.55 (m, 4 H); 2.70 (t, 2H); 3.15 (s, 2H); 3.35-3.55 (m, ÍH); 3.65 (dd, 0.76H); 3.90 (dd, 0.24H); 4.10 (t 0.76H); 4.30 (t, 0, 24 H); 6.15 (s, lH); 6.95-7.15 (m, 2 H); 7.25 (t, 1 H); 7.35 (d, lH); 7.40-7.50 (m, 3H): 7.80 (d, 0.76H); 7.90 (d, 0.24H); 8.50 (s, 0.24 H); 9.05 (s, 0.76H); 11.20 (s, ÍH). MS m / z (%): 406 (MH + 100%), 377 (5%), 244 (15%). 6-chloro-3 - [1 - [2 (1-f-ormyl-2,3-dihydro-1H-indol-3-yl) ethyl] -pyridin-4-yl] -1H-indole oxalate, 20d. Starting from 19b and 6-c-parlor-3-piper idin-4-i 1) -lflindo 1. Pf. 143-145 ° C. XH NMR (DMSO-ds), The spectrum shows a hidden rotation d 1.75-2.30 (m, 6H); 2.65-3.10 (m, 5H); 3.30-3.55 (m, 3 H); 3.65 (dd, 0.8H); 3.90 (dd, 0.2H); 4.10 (t, 0.8 H); 4.25 (t, 0.2 H); 6.95 (dd, 1H); 7.00-7.40 (m, 5H); 7.45 (d, 0.8H); 7.60 (d, lH); 7.95 (d, 0.2H); 8.50 (s, 0.2 H); 9.05 (s, 0.8H); 11.10 (s, ÍH). MS m / z (%): 410, 408 (MH + 9%, 25%), 146 (11%), 98 (100%). Oxalate of 3 - [1 - [2 (1-acet-il-5-bromo-2,3-dihydro-1H-indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] - 6-chloro-12H-indole, 20e. From 19c and 6-chloro-3- (1, 2, 3, 6-tetrahydropyridin-4-yl) -Ifl-indole. Mp 157-159 ° C X H NMR (DMS0-d 6) ', d 1.80-2.00 (m, ÍH); 2.10-2.40 (m, ÍH); 2.20 (s, 3H); 2.70 (broad s, 2 H); 3.15 (m, 2H); 3.20 (broad s, 2H); 3.45-3.60 (m, ÍH); 3.65 (broad s, 2H); 3.85 (dd, 1H); 4.25 (tH); 6.15 (s broad, ÍH); 7.10 (dd, ÍH); 7.35 (dd, ÍH); 7.45 (d, 1H); 7.55 (s, 2H); 7.85 (d, lH); 8.00 (d, ÍH); 11.45 (broad s, HI) .MS m / z (%): 502, 500.498 (MH + 8%), 27%, 22%), 297 (95%), 295 (100%). Oxalate of 3 - [1 - [2 (1-Ace ti 1-2,3-dihydro-1H-indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -7- chloro-lH-indole, "20f From 19a and 7-chloro- (1, 2, 3, 6-tetrahydropyridin-4-yl) -lH-indole, Pf. 171-173 ° C XH NMR (DMSO- dg), d 1.90-2.00 (m, HH), 2.20 (s, 3H), 2.20-2.70 (m, HH), 2.80 (broad s, 2H); 10-3.30 (m, 2H), 3.40 (broad s, 2H), 3.50 (t, ÍH), 3.80-3.95 (m, 3H), 4.25 (t, ÍH), 6.15 (s broad, ÍH), 6.95-7.15 (m, 2 H), 7.15-7.25 (m, 2 H), 7.35 (d, 1H); 7.60, (s, 1H), 7.80 (d, 1H), 8.05 (d, 1H), 11.65 (s broad, ÍH), MS m / z (%): 422.420, (MH + 3%, 7%), 174 (100%), 144 (43%). Oxalate of 3 - [1 - [2 (1-acetyl-2,3-dihydro-1H-indol-3-yl) ethyl] -1,2,3, 6-tetrahydropyridin-4-yl] -6,7-chloro-lH-indole, 20g, from 19a and 6, 7-dic loro-3 - (1,2,3,6- tetrahydropyridin-4-yl) -IH-indole, Pf 115-117 ° C XH NMR (DMSO-ds), d 1.90-2.05 (m, 1H), 2.20 (s, 3H); , 20-2.35 (m, ÍH); 2.80 (s broad 2H); 3.10-3.30 (m, 2H); 3.40 (broad s, 2 H); 3.50 (broad s, ÍH); 3.80-3.95 (m, 3 H); 4.25 (tH); 6.15 (s broad, ÍH); 7.05 (t, 1H); 7.20 (t, ÍH); 7.25 (d, 1 H); 7.35 (d, ÍH); 7.35 (d, 1H); 7.65 (s, 1H); 7.80 (d, 1H); 8.05 (d, ÍH); 11.90 (broad s, ÍH). MS m / z (%): 456, 454 (MH + 4%, 6%) 217 (36%), 174 (100%), 144 (36%). oxalate of 3- [l- [2 (l-ace ti 1 -2,2-dihydro-1H-indol-3-yl) ethyl] -1,2,3,6-te trahidro ir idin- 4-il] -5,6-I tilendioxi - ÍH- indole, 20h. Starting from 19a and 5,6-methylenedioxy- (1,2,3,6-tetrahydropyridin-4-i 1 ') - 1H-indole. Pf. 182 -183 ° C XH NMR (DMSO-ds), d 1.90-2.00 (m, 1H); 2.20 (s, 3 H); 2.20-2.30 (m, 1H); 2.75 (broad s, 2H); 3.10-3.30 (m, 2H); 3.40 (broad s, 2 H); 3.50 (broad s, ÍH); 3.80-3.90 (m, 3 H); 4.20 (t 1H); 5.95 (s, 2H); 6.05 (broad s, ÍH); 6.95 (s, ÍH); 7.05 (t, ÍH); 7.20 (t, ÍH); 7.25-7.40 (m, 3H); 8.05 (d, ÍH); 11.15 (s broad, ÍH). MS m / z (%): 430 (MH + 6%), 217 (26%), 174 (100%), 144 (62%). Oxalate of 3 - [1 - [2 (1-tert-butoxycarbonyl-2,3-dihydro-1 H -indol-3-yl) ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -6 - c loro - ÍH- indole, 20i. From 19a and 6-chloro- (1, 2, 3, 6-tetrahydropyridin-4-yl) -IH-indole. Mp 132-135 ° C XH NMR (DMSO-d6), d 1.55 (s, 9H); 1.90-2.00 (m, ÍH); 2.20-2.30 (m, HI); 2.80 (broad s, 2H); 3.10-3.25 (m, 2H); 3.40 (m 2 H); 3.40 (s at 1 i or 2 H); 3.10-3.25 (m, 2H); 3.40 (broad s, 3H); 3.65 (dd, ÍH); 3.85 (broad s, 3H); 4.10 (t, ÍH); 6.15 (broad s, 3H); 6.95 (t, ÍH); 7.10 (d, ÍH); 7.20 (t, ÍH); 7.30 (d, 1H); 7.50 (s, 1H); 7.55 (s, 1H); 7.60-7.80 (s, 1 H); 7.85 (d, 1 H); 11.60 (broad s, ÍH); 11.15 (s broad, 1 H). MS m / z (%) 478 (MH + 10%), 219 (100%), 144 (27%). 5 - [4 - [2 (1-Acet-il-2,3-dihydro-1H-indol-3-yl) ethyl] -piperazine-1-yl] -IH-indole hydrochloride, 20 j. From 19a and 5 -piperac ini 1 -IH-indole. Pf. 241 243 ° C XH NMR (DMSO-d6), d 1.95-2.15 (m, ÍH); 2,20. (s, 3H); 2.25-2.35 (m, ÍH); 3.15-3.50 (m, 6H); 3.55 (s broad, ÍH); 3.70 (d, 4H); 3.90 (dd, ÍH); 4.25 (tH); 6.40 (s, ÍH); 6, g5-7, 10 (m, 2H); 7.20 (t, 1H); 7.25-7.45 (m, 4H); 8.05 (d, ÍH); 11.10 (s, 1 H). MS m / z (%): 389 (MH +, 71%), 159 (71%), 118 (100%). Oxalate of 3 - [1 - [3 (1-acet-il-2,3-dihydro-1H-indol-3-yl) propyl] -l, 2,3,6-tetrahydropyridin-4-yl] -6- chloro-lfl-indole, 20k. From 22. Pp. 112-115 ° C XH NMR (DMSO-dg), d 1.45-1.60 (m, 1H); 1.70-1.90 (m, 3 H); 2.20 (s, 3H); 2.80 (broad s, 2H); 3.15 (broad s, 2 H); 3.30-3.50 (ra, 3 H); 3.70-3.90 (m, 3 H); 4.25 (t, ÍH); 6.15 (s broad, ÍH); 7.00 (t, ÍH); 7.10 (d, ÍH); 7.20 (t, ÍH); 7.30 (d, ÍH); 7.45 (s, ÍH); 7.55 (s, ÍH); 7.85 (d, ÍH); 8.05 (d, ÍH); 11.60 (broad s, ÍH). MS m / z (%): 436, 434 (MH + 2%, 5%), 231 (100%), 189"(36%), 158 (70%) 3- [1- [2 (l-acetyl -5-fluor-2,3-dihydro-lH-indol-3-yl) ethyl] -l, 2,3,6-tetrahydropyridin-4-yl] -6-chloro-1-yl-indole, 201. Prepared from of 19f and 6-chloro- (1,2,3,6-tetrahydropyridin-4-yl) -lH-indole. Pf .183-185 ° C XH NMR (DMSO-d6), d 1.65-1.75 (m , ÍH), 2.00-2.10 (m, 1H), 2.15 (s, 3 H), 2.40-2.55 (m, 4 H), 2.60-2.75 ( m, 2H), 3.05 - 3.25 (dd, 2H), 3.45 (bs, HH), 3.45 (bs, HH), 3.80-3.90 (m, HH); , 25 (t, lH), 6,10 (bs, ÍH), 6,95 (t, ÍH), 7,05 (d, ÍH), 7,15 (d, ÍH), 7,40 (s, 2 H), 7.80 (d, 1H), 8.05 (m, 1H), 11.20 (broad bs, IH), MS m / z (%): 438 (MH + 7%), 162 (100 %), 192 (63%), 235 (58%). 3- [1- [2 (l-acetyl-5-methyl-2 > 3-dihydro-1H-indol-3-yl) ethyl] -1,2,3,6-te-trahydropyr idin-4-yl ] -6-chloro-lH-indole, 20m. Prepared from 19g and 6-chloro- (1, 2, 3, 6-tetrahydropyridin-4-yl) -IH-indole. Mp 179-171 ° C X H NMR (DMSO-d 6), d 1.60-1.70 (m, 1 H); 1.95-2.05 (m, 1H); 2.15 (s, 3 H); 2.25 (s, 3 H); 2.40-2.60. (m, 4H); 2.65 (bs, 2H); 3.05-3.20 (dd, 2 H); 3.40 (bs, 1 H); 3.75-3.85 (m, 1H); 4.20 (t, ÍH); 6.10 (bs, ÍH); 6.90 (d, ÍH); 7.00 (d, ÍH); 7.05 (s, ÍH); 7.40 (s, 2 H); 7.80 (d, 1H); 7.90 (d, 1H); 11.25 (bs, ÍH). MS m / z (%): 434 (MH + 3%), 188 (100%), 158 (31%), 231 (21%).

Example 21 6-chloro-3 - [1 - (indan-2-ylme t i 1) piperidin-4-yl] -lH-indole oxalate, 21a To a solution of lia (0.51 g) in ethanol (40 ml) and acetic acid (10 ml) and added platinum oxide (0.12 g). The mixture was stirred for 4.5 hours under hydrogen pressure 3 atm. The mixture was filtered and evaporated in vacuo. The residue was dissolved in CH2C12 and the organic phase was stirred with dilute ammonium hydroxide and then absorbed in conventional manner to give 0.46 g of crude product, of which the titled product was crystallized as the oxalate salt from acetone. Yield 0.36 g. P.f. 229-30 ° C. XH NMR (DMSO-dg), d 1.85-2.10 (m, 4H); 2.65-3.15 (m, 10H); 3.50 (d, 2H); 7.00 (dd, ÍH); 7.20-7.20 (m, 2 H); 7.20-7.30 (m, 3H); 7.40 (d, ÍH); 7.65 (d, ÍH); 11.05 (s, 1H), MS m / z (%): 365 (MH + 100%), 249 (17%), 131 (20%). In a similar manner, the following compounds were prepared; 3 - [1- (indan-2-ylmethyl) piperidin-4-yl] -lH-indole, 21b.

P.f. 146-147 ° C. + H NMR (CDCl 3) d 1.85 (q, 2H); 2.05 (d, 2 H); 2.20 (t, 2H); 2.45 (d, 2 H); 2.65-2.90 (m, 4H); 7.20-3.00-3.20 (m, 4H), 6.95 (s 1 H); 7.05-7.30 (m, 6 H); 7.35 (d, 1H); 7.65 (d, 1H); 7.95 (broad s, ÍH). MS m / z (%): 331 (MH + 11%), 131 (11%), 98 (100%). oxalate of 7-c parrot-3 - [1 - (indan-2-ylme t i 1) pi peridin-4-yl] -IH-indole, 21 c. Prepared from 11c. P.f. 218-219 ° C. XH NMR (DMS0-d6) d 2.00-2.25 (m, 4 H); 2.70-2.85 (m, 2 H); 2.85-3.35 (m, 8 H); 3.55 (d, 2H), 7.00 (t 1H); 7.10 (t, 1H); 7.10-7.30 (m, 6 H); 7.65 (d, pH); 11.30 (broad s, ÍH). MS m / z (%): 367, 365 (MH + 9%, 25%), 131 (14%), 98 (100%). 6,7-dichloro-3- [1- (indan-2-ylmethyl) piperidin-4-yl] -lH-indole, 21d. Prepared from lid. P.f. 141-142 ° C. 1 H NMR (CDC13) d 1.75-1.90 (m, 2H); 2.00 (d, 2 H); 2.15 (t, 2 H); 2.45 (d, 2H), 2.65-2.85 (m, 4 H); 3.00-3.15 (m, 4 H); 7.00 (s, ÍH); 7.10-7.25 (m, 5 H); 7.45 (d, ÍH); 8.20 (broad s, ÍH). MS m / z (%): 401, 399 (MH + 17%, 26%), 131 (19%), 98 (100%). 3- [1- (indan-2-ylmethyl) piperidin-4-yl] -5,6-methyl-endioxy-1H-indole, 21e. Prepared from lie. P.f. 187-188 ° C. XH NMR (DMSO-d6) d 1.55-1.70 (m, 2 H); 1.90 (d, 2 H); 2.05 (t, 2 H); 2.30 (d, 2H), 2.60-2.75 (m 4H); 2.85-3.05 (m 4H); 5.90 (s, 2 H); 6.85 (s ÍH); 6.90 (s 1H); 7.00 (s 1H); 7.05-7.15 (m, 2 H); 7.15-7.25 (m, 2H); 10.55 (s broad, ÍH). MS m / z (%): 375 (MH + 10%), 131 (9%), 98 (100%). 6-Chloro-3- [1- [2- (indan-2-yl) ethyl] iperidin-4-yl] -1H-indole, 21f. Prepared from llg. P.f. 155-156 ° C. XH NMR (DMSO-d6) d 1.60 -1.75 (m, 4 H); 1.90 (d, 2 H); 2.05 (t, 2 H); 2.35-2.45 (m, 3H), 2, 45-2, 60 (m, 2H); 2.70 (t, ÍH); 2.90-3.05 (m, 4 H); 6.95 (d, ÍH); 7.05-7.20 (m, 5H), 7.35 (s, ÍH); 7.55 (d, ÍH); 10.90 (broad s, 1 H). MS m / z (%): 381,: 379 (MH + 33%, 89%), 228 (45%), 145 (44%), 98 (100%) 6-chloro-3- [1- [3- (indan-2-yl) propan-l-yl] piperidin-4-yl] -IH-indole, 21 g. Prepared from llh. P. f .134 -135 ° C. XH NMR (CDCl 3) d 1.45-1.60 (m, 2H); 1.75-1.90 (m, 2H); 2.05 (d, 2H); 2.10 (t, 2H); 2.35-2.55 (m, 3H); 2.55 - 2.65 (m, 2H); 2.80 (t, ÍH); 2.95-3.15 (m, 4H) 6.95 (s, ÍH); 7.00-7.25 (m, 5H), 7.30 (s, 1H); 7.55 (d, 1H); 8.10 (broad s, 1HI, MS m / z (%): 395, 393 (MH + 8%, 21%), 242 (53%), 117 (52%), 98 (100%). -3- [1- [4- (indan-2-yl) butan-l-yl] piperidin-4-yl] -IH-indole, 21h. Prepared from lli.Pf 139-140 ° C. XH NMR (CDCl 3) d 1.30-1.70 (m, 6H), 1.70-1.95 (m, 2H), 1.95-2.20 (m, 4 H); 2.35-2, 65 (m, 5 H), 2.70-2.90 (m, HH), 2.95-3.15 (m, HH), 2.95-3.15 (m, 4H), 6.95 (d, HH), 7.00-7.25 (m, 5H) *, 7.35 (d, HH), 7.55 (d, HH), 8.05 (s broad, HH). / z (%): 409, 407 (MH + 32%, 90%), 256 (96%), 98 (100%).

For example, 22 l-acetyl-3- (3-bromo-propane-1-yl-2, 3-dihydro-H-nature, 22 (Intermediate) A mixture of 3- (1 H-indol-3-yl) propionic acid (10 g.), Methanol (200 ml) and a saturated solution of HCl in ether (75 ml) was stirred at room temperature for 4 days. . The solvents were removed in vacuo and the residue was absorbed in a conventional manner by the use of dilute ammonium hydroxide and ethyl acetate to give an oil (10.6 g.). The oil was dissolved in acetic acid (200 ml) and NaCNBH4 (12 g.) Was added in parts of 1 g. The mixture was stirred at room temperature for 48 hours and then poured into ice-cooled water. The pH of the solution was adjusted to 8 with ammonium hydroxide (25%) and the aqueous phase was extracted with ether. The combined organic phase was extracted with 1 M HCl solution. The pH of the solution was adjusted to 8 with ammonium hydroxide and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4) and the solvent was extracted in vacuo. The residue was purified on silica gel, eluted with ethyl acetate (1: 1) to give an oil (6.1 g), the residue was dissolved in THF (50 ml) and added to a suspension of LiAlH4 (2.0 g.) in THF (100 ml) at about 30 ° C. The mixture was stirred at room temperature for 15 minutes and then cooled to 5 ° C. By drip addition, water (4 g) was added. , 0 ml.), 15% NaOH solution (2.0 ml.) And water (10 ml.) The mixture was dried (MgSO.sub.4) and concentrated in vacuo.The oil was dissolved in THF (200 ml), triethylamine (11 ml) was added and cooled to -20 ° C. To this mixture, a solution of acetyl chloride (2.1 ml.) in THF (50 ml) was added, and the mixture was heated to 50 ml. 5 ° C. A solution of methanesulfonyl chloride (2.1 ml) in THF (50 ml) was added to this mixture, ether (200 ml) was added and the mixture was filtered, the mother liquor was concentrated in vacuo and subject to purification on silica gel eluted with ethyl acetate et i lo -hep taño (500 ml. ), lithium bromide (10.3 g.) was added and the mixture was boiled under reflux for one hour. The mixture was cooled, filtered and evaporated in vacuo to dryness, to give the titled compound.

Example 7 7-methoxy-1-indanecarboxylic acid, 23a To a mixture of 7-methoxy-1-indanone (25 g.) Prepared according to J. Am. Chem. Soc., 1948, 70, 1386, Znl2 (0.5 9.) in toluene (300 ml.), Triamotetracyclic cyanide (25 ml. And then 15 ml. After 3 hours) was added. ) and the reaction mixture was stirred at 60 ° C for 5 hours. Water was added, and the mixture was stirred at room temperature for one hour. The phases separated; and the organic phase was dried (MgSO4) and evaporated to dryness in vacuo. The residue was purified on silica gel eluted with dichloromethane (9. 9.) The residue was dissolved in acetic acid (100 ml) and 6M HCl solution (100 ml) and the mixture was heated at 100 ° C for 7 hours. The acetic acid was extracted in vacuo, and the aqueous phase was extracted with ether The combined organic phases were dried (MgSO 4) and evaporated to dryness and purified on silica gel eluted with dichloromethane (5 g). The residue was dissolved in ethanol (200 ml), palladium on charcoal (5%) (2 g) was added to the solution, and the mixture was stirred for 3 hours under 3 atm of hydrogen pressure.The mixture was filtered and evaporated in vacuo (5 g) The residue was purified on silica gel, eluted with ethyl acetate-heptane (1: 4) to give an oil (28.4 g, 87%).

Example 24 2 - (2-iodoe ti 1) indane, 24a (Intermediate) A mixture of 2- (indan-2-yl) ethanol (19.3 g), imidazole (12.1 g *), was heated, trif enylphosphine (34.3 g.) and toluene (250 ml) at 90 ° CA this mixture, iodine (33.2 g.) was added and the resulting mixture was stirred at 90 ° C for 20 minutes. The mixture was cooled to room temperature, filtered and concentrated in vacuo. The residue was purified on silica gel, eluted with ethyl acetate-heptane (1: 4) to give an oil (28.4 g, 87%).

For example, 4- 4- [4- [2- (indan-2-yl) ethyl] piperazin-1-yl] -lH-indole, 25a. A mixture of 4- (piperac in- 1-i 1) -lH was maintained. -indole (1.5 g.), 2- (2-iodoe ti 1) indane (2.0 g.), K2CO3, methylisobutyl ketone (150 ml.) and N. I t -pyrrolidone (10 ml), boiling under reflux for 3 hours. The mixture was cooled to room temperature, filtered, and concentrated in vacuo. The residue was purified on silica gel, eluted with ethyl acetate. (1: 2) to give a crystalline compound, which was recrystallized (ethyl acetate) to give the titled compound (1.2 g, 47%). P.f. 146-147 ° C. XH NMR (CDClj) d 1.70-1.85 (m, 2 H); 2.40 2.70 (m, 5H); 2.75 (broad s, 4H); 3.00-3.15 (m, 2H) 3.30 (broad s, 4H) 6.55 (s, ÍH); 6.60 (d, 1 H); 7.00-7.30 (m, 7H); 8.20 (broad s, MS m / z (%): 346 (MH + 34%), 159 (88%), 145 (100%). Similarly, the following compound was prepared: 5 - [4 -] hydrochloride [2 - (indan-2-yl) ethyl] -perazin-1-yl] -IH-indole, 25b, prepared 2.40-2.55 from 24a and from 5 - (piperazin-1-yi) - lH-indole, MP 251-253 ° C. XH NMR (DMSO-d d 1.970-2.05 (m, 2H), (m, HH); 2.55-2.70 (m, 2H); 00-3.15 (m, 2H), 3.25 (broad s, 2H), 3.50 (broad s, 2H) 3.75 (broad s, 6H), 6.45 (s,, 1H); 7.05-7.30 (m, 5H) 7.40 (s, HH), 7.45 (d, HH), 7.55 (broad s, HH) 11.60 (broad s, HH). m / z (%): 346 (MH + 44%), 159 (87%), 145 (100%).

Example 26 5-Chloro-1 - (pyridin-4-yl) -1-H-indole, 26a (Intermediate) A mixture of 5-chloro-1-H-indole (20 g), 4-bromopyridine, was heated, HCl (45 g.), K2C03 (55 g.), CuBr (5 g.) And Cu (2 g.) At 150 ° C for 24 hours. The reaction mixture was cooled, poured into water (700 ml) and the crude product was collected by filtration. The crude product was dissolved in ethyl acetate (1000 ml.) And the organic phase was washed with dilute ammonium hydroxide and saturated NaCl solution. The organic phase was dried (MgSO and concentrated in vacuo (150 ml). The crystalline compound 5-chloro-1 - (pyrid4-yl) -IH-indole was collected by filtration (18.0 g, 60%).

In a similar manner, the following compound was prepared: 1- (pyridin-4-yl) -IH-indole, 26b Example 27 2 - (pyridin-4-yl) -IH-indole, 27a (Intermediate) A mixture of isonicotic acid (7.1 g.) And thionyl chloride (150 ml.) Was kept under boiling under reflux for 2 hours. hours and evaporated to dryness in vacuo. The residue was dissolved in DMF (100 ml) and added to a suspension of 2-aminobenzyl phenyl phosphonium bromide (L: Capuano et al., Cehm Ber 1986, 119, 2069-2074) in dichloromethane. The resulting clear solution was stirred at room temperature for two hours and concentrated in vacuo. The crude product was recrystallized (ethanol) to give 21.3 g. of crystals. The compound corresponding to 1.0 g. it was suspended in toluene (25 ml) and the mixture was heated to reflux temperature. Potassium tert-butoxide (0.44 g) was added immediately, and the reaction mixture was boiled under reflux for 15 minutes; then it was filtered hot and concentrated in vacuo. The residue was purified on silica gel, eluted with ethyl acetate and ilo-hept ano-TEA (80: 20: 5) to give the titled compound.

Example 28 5-Chloro-l- [1- [2- (indan-2-yl) -ethyl] -1,2,3,6-tetrahydropyridin-4-yl] -lH-indole, 28a, Was maintained in boiling under reflux a mixture of 5-c parrot-1 - (pyridin-4-y1) -1H-indole 26a (4.0 9.), 2- (2-iodoethyl) indane 24a (4.8 9.) me t i 1 i sobut i 1 ketone (100 ml), for 20 hours. The mixture was cooled, and a crystalline compound was collected by filtration (6.5 g.). The compound corresponding to 5.5 g. was suspended in methanol (100 ml) and NaBH 4 (1.5 g.) Was added in portions of 0.5 g. The resulting mixture was stirred at room temperature for one hour and the solvent was removed in vacuo. The preparation was carried out in a conventional manner with ethyl acetate and water, followed by purification on silica gel eluted with ethyl acetate-heptane (1: 1) which gave the crude product, which was crystallized (ethyl acetate) to give the compound titled (l, lg., 27%) Pf 93-94 ° C. XH NMR (CDCl 3) d 1.75-1.90 (m, 2 H); 2.45-2.55 (m, ÍH); 2.55-2.70 (m, 6H); 2.75-2.90 (m, 2H); 3.05-3.15 (m, 2H); 3.25 (d, 2H); 5.90 (broad s, ÍH); 6.45 (s, ÍH); 7.05-7.25 (m, 6H); 7.45 (d, lH); 7.60 (s, ÍH). MS m / z (%): 377 (MH + 6%), 143 (100%), 128 (50%). In a similar manner, the following compound was prepared: 1- [1- [2- (indan-2-yl) -ethyl] -l, 2,3,6-tetrahydropyridin-4-yl] -lH-indole oxalate, 28b.

Prepared from 24a and 26b. P.f. 176-178 ° C. XH NMR (DMS0-d6) d, 85-1, 95 (m, 2H); 2.40-2.55 (m, 1 H); 2.55-2.70 (m, 2 H); 2.85 (broad s, 2 H); 3.00-3.10 (m, 2H); 3.15 (t, 2H); 3.40 (broad s, 2H); 3.85 (broad s, 2H); 5.95 (broad s, ÍH); 6.60 (d, 1H); 7.05-7.25 (m, 6 H); 7.55 (d, 1H); 7.60-7.70 (m, 2H). MS m / z (%): 343 (MH +), 143 (100%), 128 (80%). 2- [1- [2- (indan-2-yl) -ethyl] -1,2,3,6-te trahidropir idin4-i 1] - ÍH-indole, 28c. Prepared from 27a and 24a. P.f. 175-176 ° C. XH NMR (CDC13) d 1.75-1.85 (m, 2H); 2.40-2.55 (m, ÍH); 2.55-2.60 (m, 2 H); 2.60-2.70 (m, 4 H); 2.70-2.80 (m, 2H); 3.05-3.15 (m, 2H); 3.25 (broad s, 2 H); 6.05 (broad s, ÍH); 6.45 (s, ÍH); 7.05 (t, ÍH); 7.10-7.25 (m, 5H); 7.35 (d, ÍH); 7.55 (d, ÍH); 8.10 (broad s, ÍH). MS m / z (%): 343 (MH + 8%), 174 (32%), 143 Example 29 5-chloro- [1- [2- (indan-2-yl) -ethyl] piperidin-4-yl] -1H -indole, 29a, A mixture of 5-chloro- [1- [2-indan-2-yl) -methyl] -1, 2,3,6-tetrahydropyridin-4-yl] -1H-indole, 28a was stirred, (1.9 g.) Acetic acid (50 ml) and platinum oxide (0.1 g.), For 3 hours under hydrogen pressure 3 atm. The mixture was filtered and evaporated in vacuo. The residue was dissolved in ethyl acetate and the organic phase was stirred with dilute ammonium hydroxide and then worked in a conventional manner. Purification was carried out on silica gel, eluted with ethyl acetate and iloheptide (1: 1) to give 2.0 g. of the raw product. The crude product was crystallized (ethyl acetate) and the titled compound was collected by filtration (1.1 g, 58%). P. f .108-109 ° C. X H NMR (CDCl 3) d 1.70-1.80 (m, 2 H); 2.00-2.10 (m, 4 H); 2.10-2.25 (m, 2 H); 2.40-2.55 (m, 3H); 2.55-2.70 (m, 2H); 3.00-3.20 (m, 4H); 4.10-4.25 (m, ÍH); 6.45 (d, ÍH); 7.05-7.35 (m, 7H); 7.60 (s, ÍH). MS m / z (%): 379 (MH + 3%), 223 (13%), 145 (29%), 143 (28%), 98 (100%). In a similar manner, the following compound was prepared: 1- [1- [2- (indan-2-yl) -ethyl] piperidin-4-yl] -lH-indole, 29b. Prepared from 28b. P.f. 80-81 ° C.xH NMR (CDC13) d 1.70-1.85 (m, 2H); 2.00-2.25 (m, 6H); 2.40-2.55 (m, 3 H); 2.55-2.70 (m, 2 H); 3.00-3.20 (m, 4 H); 4.15-4.30 (m, 1H); 6.50 (d, 1H); 7.05-7.30 (m, 7H); 7.40 (d, ÍH); 7.65 (d, ÍH); , MS m / z (%): 345 (MH + 4%), 228 (9%), 145 (30%), 143 (34%), 98 (100%).

For example, 6-chloro-3 - [1 - [2 - (2, 3-dihydro-1H-indol-3-yl) -ethyl] -l, 2,3,6-tetrahydropyridin-4-ethyl] -lH oxalate -indole, 30a, A mixture of 3- [1- [2- (1-tert-butoxycarbonyl-2,3-dihydro-1H-indol-3-yl) etl] -2, oxalate mixture was cooled. 3,6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 20i, as a base fiber (4.0 g.), Dichloromethane (50 ml) and THF (25 ml) were added in an ice bath and t r i f luoracé tico acid (40 ml) was added to the mixture. The reaction mixture was stirred at room temperature for 16 hours and poured into an ice-cooled solution of dilute ammonium hydroxide. Conventional absorption with ethyl acetate gave the crude product. The crude product corresponding to 1.4 9. was converted to the oxalate salt, which was recrystallized (meth anol-etherheptane) to give the titled compound (0.5 g) P. f.109-111 ° C. XH NMR (DMSO-d6) d 1.80-2.00 (m, ÍH); 2.10-2.30 (m, 1H); 2.80 (broad s, 2H); 3.05-3.35 (m, 4H); 3.35-3.65 (m, 3H); 3.90 (broad s, 2H); 6.15 (s broad, ÍH); 6.45-6.65 (m, 2H); 6.95 (t, 1 HOUR ); 7.00-7.15 (m, 2 H); 7.45 (d, 1H); 7.60 (d, 1H); 7.85 (d, 1H); 11.55 (d, ÍH) MS m / Z (%): 378 (MH + 4%), 169 (19%), 168 (38%), 144 (100%). In a similar manner, the following compound was prepared: 6-chloro-3- [1- [4 (2,3-dihydro-lH-indol-3-yl) -butan-1-yl] - 1, 2, 3, 6-tetrahydropyridin-4-yl] -1H-indole, 30b. A part from 19 e.

It employs 6-chloro-3 - [1 - [2 - (2, 3-dihydro-1-methylaminocarbonyl -H-indol-3-yl) -ethyl] 1,2,3,6-tetrahydropyridine oxalate - 4-yl] -lH-indole, 31a, To a solution of 6-chloro-3- [1- [2 - (2,3-dihydro-1H-indole-3-yl) -ethyl] oxalate] 1,2,3,6-te trahydropyr idin-4-yl] -1 H-indole, 30a, as free base in dichloromethane (100 ml) was added 1 i socianat or (1.4 g.) In dichloromethane (20 g). ml.). The mixture was stirred at room temperature for 16 hours and the solvent was removed in vacuo. The residue was purified on silica gel, eluted with ethyl acetate - triethyl acetate (90: : 5) to give the crude product, which was recrystallized (methanol-ethyl acetate) to give the titled compound (1.8 g.). X H NMR (DMSO-d 6) d 1.60-1.70 (m, 1H); 1.95-2.05 (m, 1H); 2.40-2.60 (m, 4H); 2.60-2.75 (m, 5H); 3.15 (q, 2H); 3,35-3,50 (m, 1H); 3.55-3.65 (m, ÍH); 4.00 (t, ÍH); 6.10 (s, broad, ÍH); 6.55 (d, ÍH); 6.85 (t, ÍH); 7.05 (d, lH); 7.10 (t, lH); 7.20 (d, 1H); 7.45 (s, 2 H); 7.80 (d, ÍH); 7.85 (d, ÍH); 11.25 (broad s, HI) MS m / z (%): 437, 435 (MH + 2%, 6%), 201 (54%), 189 (100%), 144 (64%).

The acetate (+ / -) - methyl (1-tert-butoxycarbonyl-2,3-dihydro-lH-indol-3-yl) 32a was used. (Intermediate) A mixture of (IH-indole-3-yl) acetic acid (62 g.), Methanol (800 ml.) And a saturated solution of HCl in ether (200 ml.) Was stirred at room temperature. 4 days. The solvents were removed in vacuo, and the residue was worked up or in a conventional manner by the use of dilute ammonium hydroxide and ethyl acetate to give an oil (64 g.) - The oil was dissolved in acetic acid (600 ml) and NaCNBH4 (27.6 g.) Was added in portions of 1 g. The mixture was stirred at room temperature for 48 hours and then poured into water cooled on ice. The pH of the solution was adjusted to 8 with ammonium hydroxide (25%) and the aqueous phase was extracted with ethyl acetate (3 x 11). The combined organic residue was then dissolved in THF (500 ml.) And a solution of di-tert-butyl dicarbonate (89 g.) In THF (500 ml) was added to this mixture. The reaction mixture was stirred at room temperature for 24 hours and the solvent was removed in vacuo. The crude product was purified on silica gel, eluted with ethyl acetate-heptane (1: 4) to give the title compound as an oil (92 g).

Use of (+) - (1-tert -butoxycarbonyl-2,3-dihydro-1H-indol-3-yl) acetic acid 33a. (Intermediary) Lipase Candida Antarctica (CAL, SP-435, Novo Nordisk, Denmark) (2.5 9.) was suspended in (+/-) -methyl acetate (1-tert-but-oxycarboni 1,2-, 3-dihydro-1H-indol-3-yl) 32a (50 g.) And this mixture was further suspended in 0.1 M phosphate buffer (pH 7.0) (3 1) under vigorous stirring. The reaction mixture was maintained at 25 ° C and the pH was maintained at 7 by the addition of 0.5 M NaOH solution. The reaction could be. monitored by the aggregate amount of NaOH and was stopped after the addition of approximately 0.45 equivalent of base (approximately 120 h.). The enzyme was filtered and washed with ether (1 1). The pH of the aqueous phase was adjusted to 8. The aqueous phase was extracted with ether. (2 x 1 1). The combined organic extracts were dried (MgSO4) and evaporated to dryness in vacuo to give the initial ester enriched in a single enantiomer. The aqueous phase was cooled with ice and the pH was adjusted to 1.5 by the addition of concentrated HCl. The aqueous phase was extracted with ether (3 x 11). The combined organic extracts were dried (MgSO4) and the solvent was extracted in vacuo to give the titled compound in an enantiomeric excess of about 80-85%. Recrystallization from diisopropyl ether gave the titled compound in an enantiomeric excess of 96.5% [a] D = + 128 ° (c = 0.45, methanol). P.f.137-1 38 ° C. (-) - (1-tert-butoxycarboni 1,2-, 3-dihydro-1H-indol-3-yl) acetic acid 33b. The ester enriched from the synthesis of 33a was treated once more, as described for racemate 32a and the reaction mixture prepared in a manner similar to 33a. The ester enriched in a single enantiomer corresponding to 33.7 g. was dissolved in ethanol (500 ml) and treated with 1M NaOH solution (500 ml). The mixture was stirred at room temperature for 30 minutes and the ethanol was extracted in vacuo. The aqueous phase was extracted with ether (3 x 400 ml.) And the combined organic extracts were washed with brine, dried (MgSO.sub.4) and the solvent was extracted in vacuo (31 9., enantiomeric excess of 94.6%). The residue was crystallized from diisopropyl ether (50 ml.) To give the titled compound in an enantiomeric excess of 97.7% (26 g.). [α] D = + 12.6 ° (c = 0.47, methanol). P.f. 136-137 ° C. The chiral HPLC analysis was performed in an apparatus equipped with a UV detector (set at 230 nm). The analysis was developed in an Ultron ES OVM 150 x 4.6 mm, flow 1.0 ml / min, phosphate buffer eluent 25 mM (pHJ 4.6) / methanol / isopropanol / THF 90/5/5 / 0.5 , T = 30 ° C. The enantiomeric purities expressed as enantiomeric excess (ee) were calculated from peak areas.

Example 34 (+) - (3- [1- [2- (1-acetyl-2,3-dihydro-1H-indol-3-yl) -ethyl] -1,3,6-tetrahydropyridin-4 -yl] -lH-indole, 34a, A mixture of (+) - (1-tert-butoxycarbonyl-2,3-dihydro-lH-indol-3-yl) acetic acid 33a (5.0 g.), methanol (200 ml.) and a saturated solution of HCl in ether (50 ml.) was stirred at room temperature for 16 hours.The solvent was removed in vacuo, and the residue was dissolved in ice water on ice. The mixture was washed with ether and the pH was adjusted to 8 with a saturated solution of NaHCO 3 The aqueous phase was extracted with ethyl acetate (3 x 150 ml), and the combined organic extracts were washed with brine (MgSO 4), and evaporated until dryness in vacuo (3.4 g.) The residue was dissolved in THF (50 ml) and added to a suspension of LiAlH4 (1.6 9.) in THF (150 ml.) at about 30 ° C. was stirred at room temperature for 30 minutes and then cooled to 5 ° C. By drip addition, it was added Water (3.2 ml), 15% NaOH solution (1.6 ml. ) and water (8 ml.). The mixture was dried (MgSO and concentrated in vacuo) The residue was purified on silica gel, eluted with ethyl acetate-ethanol (200: 5) to give an oil (2.6 9.) The oil was dissolved in dichloromethane (80 ml.), Triethylamine (2.7 ml.) Was added and cooled to 30 ° C. To this mixture, a solution of acetyl chloride (1.1 ml.) In dichloromethane (10 ml.) Was added. and the mixture was heated to 5 ° C. Then triethylamine (2.7 ml) was added and to this mixture, a solution of methanesulfonyl chloride (1.3 ml.) in dichloromethane (10 ml.) was added. The reaction was purified on silica gel eluted with ethyl acetate-heptane (4: 1) to give oil (4.5 g) The oil was dissolved in methylisobutyl ketone (100 ml) and added to a mixture of 6-chloro-3- (1,2,3,6-tetrahydropyridin-4-yl) -1H-indole (5.5 g.), K2C03 (4.4 g.), Methylisobutyl ketone (100 ml) and N-met i Ipirrol idone (10 ml.) Under reflux. The mixture was boiled under reflux for 6 hours and evaporated to dryness in vacuo. The residue was purified on silica gel, eluted with ethyl acetate-ethanol (10: 1) to give the crude product, which was recrystallized (ethyl acetate) to give the titled compound (2.9 g.) In a Enantiomeric excess of 97.4% [a] D = + 35.9 ° (c = 0.25, methanol). P.f. 169-170 ° C. XH NMR (DMSO-d6) d 1.65-1.80 (m, 1H); 2.00-2.10 (m, 1H); 2.15 (s, 3 H); 2.45-2.60 (m, 4H); 2.65 (broad s, 2H); 3.05-3.20 (m, 2H); 3.40-3.50 (m, ÍH); 3.80 (dd, 1H); 4.25 (t, ÍH); 6.10 (s, broad, ÍH); 6.95-7.05 (m, 2H); 7.15 (t, 1H); 7.30 (d, 1H); 7.40-7.45 (m, 2 H); 7.80 (d, 1 H); 8.05 (d, ÍH); 11.20 (broad s, HI) MS m / z (%): 422, 420 (MH + 3%, 8%), 217 (30%), 174 (100%), 144 (41%). In a similar manner, the following compound was prepared: (-) - (3- [1- [2- (1-acetyl-2,3-dihydro-1H-indol-3-yl) -ethyl] -1, 2,3,6-tetrahydropyridin-4-yl] -6-chloro-lH-indole, 34b The enantiomeric excess of 98.4%. [] D = -34.9 ° (c = 0.27, methanol) Mp 168-169 ° C Chiral HPLC analysis was performed on an apparatus equipped with a UV detector (set at 230 nm) The analysis was developed in a Chira AGP x 4 mm, flow 0.8 ml / min, Phosphate buffer eluent 25 mM (pH = 4.6) / methanol / isopropanol / THF 9 0/5/5/1, T = 25 ° C. The enantiomeric purities expressed as enantiomeric excess (ee), were calculated from areas peak.

The use of 3- 3- [1- [4- (l-acetyl-2, 3-ihydro-lH-indol-3-yl) -butan-1-yl] -1,2,3,6-tetrahydropyridin-4 il] -6-chloro-lH-indole, 35. A mixture of 3 - [1 - [4 - (2, 3-dihydro-1-H-indol-3-yl) -butan-1-yl] -1 , 2,3,6-tetrahydropyridin-4-yl] -IH-indole, 30b (4.9 g.), Triethylamine (3.7 g.) And THF (200 ml.), Was cooled (5 ° C). and the mixture was added to a solution of acetyl chloride (1.0 g.) in THF (50 ml.). The reaction mixture was warmed to room temperature, filtered and concentrated in vacuo. The residue was purified on silica gel, eluted with ethyl acetate-e tanol-triethyl sheet (90: 10: 5) to give the crude product, which was recrystallized (me tanol-et-il-acetatol to give the titled compound (2.7 g.) XH NMR (DMSO-dg) d 1.30-1.45 (m, 2H); 1.45-1.60 (m, 3H); 1.75-1.85 (m, ÍH); 2.15 (s, 3H); 2.40 (t, 2 H); 2.45-2.55 (m, 2 H); 2.55-2.65 (m, 2 H); 3.10 (broad s, 2H); 3.40 (s broad, HH, 3.70-3.80 (m, HH), 4.20 (t, HH), 6.10 (s, broad, HH), 6.95 (t, 1H); 7.05 (d, 1H); 7.15 (t, 1H); 7.25 (d, 1H); 7.40 (s, 2H); 7.80 (d, 1H); (d, 1 H), 11.20 (broad s, 1 H).

Example 36 2, 3-dimethyl-1- (2-propyl) oxybenzene, 36a (Intermediate) To a stirred solution / suspension of 2,3-dimethylphenol (10 g.) And potassium carbonate (6.8 g.) In acetone (150 ml) at reflux, 2-bromopropane (46 ml) was added dropwise over 30 minutes. The solution was heated to reflux for 4 days. After cooling, the solvent was evaporated and the residue was dissolved in ether and water. The ether phase was separated and absorbed according to the general procedure. Column chromatography on silica gel (eluent: ethyl acetate / heptane 1:19), gave 2,3-dimet i 1 - 1 - (2-propy1) oxybenzene (13.2 g.) Pure, as mobile , slightly brown oil which was used without further purification.

Example 37 2, 3-i (bromomethyl) -1- (2-propyl) oxybenzene, 37a (Intermediate) To a stirred solution / suspension of 2.3 dimet i 1 - 1 - (2 -propi 1) oxybenzene (10 g.) and carbon tetrachloride (150 g.) was added N-bromosuccinimide (22 g.) and dibenzoyl peroxide (370 mg) and the mixture was heated under reflux for 1.5 hours. The solution was cooled to room temperature and filtered. The residue was washed with carbon tetrachloride (100 ml.) And the combined filtrates were evaporated to give 2,3-di (bromomethyl) -1- (2-propyl) oxybenzene (21.0 g.), As an oil. yellow / orange, which was used without further purification.

Example 38 Diethyl 4- (2-propyl) oxlindan-2,2-dicarboxylate, 38a Sodium hydride (7.7 g, 50-60% dispersion in oil) was rendered oil-free by washing with heptane (twice) . This was then added to a solution of 2,3-di (bromome-t-1) -1- (2-propy1) oxybenzene (21 9.) in THF (600 ml) and the solution was heated to reflux. After one hour, the solution was cooled to room temperature, and water (200 ml.) Was added dropwise to decompose the excess sodium hydride. The mixture was poured into aqueous hydrochloric acid (500 mL, 3M) and extracted with ethyl acetate (3 x 300 mL). The general absorption procedure gave a dark oil, which was purified by column chromatography on silica gel (eluent: ethyl acetate / heptane 1: 9) to give diethyl 4 - (2 -propi 1) oxy indan-2, 2 -dicarboxylate (11.5) as light oil, which was used without further purification.

Use 39 4- (2-propyl) oxy indan- 2, 2-icarboxylic acid, 39a (Intermediate) A solution / suspension of diethyl 4- (2-propy1) oxy indan-2, 2-dicarboxy lat (11.5 9.) in potassium hydroxide (50 ml., 3M) was heated to reflux for 18 hours. The solution was cooled to room temperature and extracted with ether. The aqueous solution was acidified at pH < 1 with hydrochloric acid (3 M) and extracted with ethyl acetate. Conventional absorption gave 4- (2-prop i 1) oxy indan-2,2-dicarboxylic acid (8.5 g.) As brown solid, which was used without further purification.

For example, 4 - (2-propy1) oxy-2-diene-2-dicarboxylic acid, 40a (intermediate) A solution of 4- (2-propyl) oxy-2- (2, 1-dicarboxylic acid (11.5 g.) In NMP) (20 ml.) Was heated to 150 ° C. After 15 minutes the solution was cooled to room temperature and poured into aqueous hydrochloric acid (1500 ral., 1 M). This mixture was extracted with ethyl acetate (2 x 500 ml.) And a standard absorption gave 4- (2-propyl) oxy indan-2-dicarboxylic acid (3.98 g.) As a dark brown solid, which was used without further purification.

Pharmacological Test The compounds of the invention were tested in reliable and well-recognized methods. The tests were the following: Ligation of 3H-YM-09151-2 By this method, the inhibition by drugs of ligation of dopamine antagonists D4 3H-YM-09151-2 to dopamine D4 receptors in cloned membranes subtype 4.2 of human dopamine receptors, It is determined in vitro. Therefore, this is an affinity test for dopamine D4 receptors. The test is carried out by means of a preparation of cloned dopamine cell membranes D4 (CRM-016®, Dupharma A / S, Denmark, according to the product specifications .The results are given in the following Table as IC50 values.

Table 1: Ligation Data (IC50 values in nM or% inhibition of ligation at 50nM (* means that the result of the test is preliminary, nt; means not tested).

Ligation of 3H-8-0H-DPAT Using this method, the inhibition by drugs of the ligation of the agonist 5-HT, A 3H-8-OH-DPAT (1 nM) with 5-HT1A in brain membranes of mice less cerebellum , it is determined in vitro. Therefore, this is a test to achieve the affinity of the 5-HT'A receptor. The test is developed as described by Hyttel et al., Drug (Dev.) Dev. Res., 1988, 15, 389 404. 3H-Ke tanserine binding Using this method, the inhibition by drugs of the 3H-Ke tanser ina ligation (0.5 nM) with 5-HT1A receptors in the membranes of mice is determined in vitro. The method is described in Hyttel, "Pharmacology &Toxicology", 61, 126-129, 1987. In addition to the preceding tests, the compounds of the invention were analyzed in relation to an affinity of the dopamine receptors. D2 by determining its ability to inhibit ligation of the 3H-spiroper idol with D2 receptors by the method of Hyttl et al., J. Neurochem., 1985, 44.1615. In addition, the compounds were analyzed for their inhibitory effect on 5-HT reabsorption by measuring their ability to inhibit the uptake of 3H-serotonin in the synaptosomes of the whole rat brain in vitro. The assay was developed as described in Hyttel, J. Psychophar acology (Ps icof armacologia), 1978, 60, 13. In general, it has been found that the compounds of the invention are potential to inhibit the binding of YM-09151- 2 tritiated with dopamine D4 receptors. In addition, it has been proved that many compounds inhibit the binding of 8-hydroxy .2-dipropylaminotte ral in tritiated (8-OH-DPAT) with 5-HT1A receptors and / or the binding of 3H-ketanserin to receptors. -HT2A in vitro. Some compounds only bind to one of the two subtypes of serotonin 5-HT1A or 5-HT2A receptors. The compounds have no substantial or only weak affinity for the dopamine D2 receptor. The VTA model is used to examine the effects on spontaneous active DA neurons in the ventral tegmental area (VTA), indicating an antipsychotic effect of a compound. The VTA model is more fully described in European Patent No. A-2392958, page 4.

Some of the compounds of the invention have been analyzed and were effective in reducing the number of active DA neurons in the VTA. Accordingly, the compounds of the invention are considered useful in the treatment of positive and negative symptoms of schizophrenia, other psychoses, anxiety disorders, such as generalized anxiety disorder, panic disorder, and obsessive compulsive disorder, depression, alcohol abuse, disorders to control impulses, aggression, collateral effects induced by conventional antipsychotic agents, pathological states of ischemia, migraine, senile dementia, and cardiovascular disorders and in the improvement of sleep. In particular, the compounds of the invention are useful in the treatment of positive and negative symptoms of schizophrenia without inducing side effects ext rapiramidales.

Formulation Examples The pharmaceutical formulations of the invention can be prepared by methods conventional in the art.

For example: the tablets can be prepared by mixing the active ingredient with ordinary adjuvants and / or diluents and subsequently compressing the mixture from a conventional tablet machine. Examples of adjuvants or diluents comprise: corn starch, potato starch, magnesium stearate, gelatin, lactose, gums and the like. Any other adjuvant and additive generally used for such purposes as dyes, flavors, preservatives, etc. , can be used, as long as they are compatible with the active ingredients. Solutions for injections can be prepared by dissolving the active ingredient and possible additives in a part of the solvent to be injected, preferably sterile water, adjusting the solution to the desired volume, sterilizing the solution and filling in ampoules or suitable bottles. Any suitable additive conventionally used in the art can be added, such as tonicity agents, preservatives, antioxidants, etc. The following examples are typical examples of recipes for the formulation of the invention: 1) Tablets containing 5.0 mg. of compound 4 = calculated as free base: Compound 5a 5.0 mg. Lactose 60 mg. Corn starch 30 mg. Hydroxypropylcellulose 2.4 g. Cellulose microcrist inal 19.2 g. Croscarmellose Sodium Type A 2.4 g. Magnesium stearate 0.84 mg 2) Tablets containing 5.0 mg. of compound 21 calculated as free base: Compound 21 5.0 mg. Lactose 46.9 mg. Corn starch 23.5 mg. Povidone 1.8 g. Microcrystalline cellulose 14.4 g. Croscarmellose Sodium Type A 1.8 g. Magnesium stearate 0.63 mg. 3) Syrup containing per millimeter the following: Compound 21 25 mg. Sorbitol 500 mg Hydroxypropylcellulose 5 mg. Glycerol 50 g. Methylparaben 1 g.

Propylparaben 0.1 g. Ethane 1 0.005 ml Taste 0.05 mg Sodium saccharin 0.5 mg Water 1 ml. ad 4) Solution for injections containing per millimeter the following: Compound 4a 0, 5 g Sorbitol 5, 1 mg Acetic acid 0.05 mg. saccharin sodium 0.5 mg. Water 1 ml. Having thus, especially, described and determined the nature of the present invention and the manner in which it is to be put into practice, it is declared to claim as property and exclusive right:

Claims (61)

1. A substituted compound of indane or of dihydroindole of formula I Y is a hydrocarbon group that completes an indane ring, an NR1 group that completes a dihydroindole ring or an N group, which completes a dihydroindole ring bound via position 1; • W is a bond and n + m is 1, 2, 3, 4, 5 or 6: • W is CO, SO, or S02, n is 2, 3, 4 or 5 and m is 0, 1, 2, or 3 provided that n + m is not more than 6; or • W is O, S, n is 2, 3, 4, Ó 5 and m is 0, 1, 2, or 3, provided that n + m is not more than 6; and when Y is N by completing a hydroindol ring bound to position 1, then m is 2 or 3 and when Y is NR 'completing a dihydroindole ring bound via position 2, then m is 1, 2 or 3, the line of points, emanating from X, indicates an optional link; when it does not indicate a link X is N, CH or COH; and when it indicates an X link; is C; Rxes: • hydrogen, alqu (in / in) i lo Cx.g, cic loalqu (alen / in) i lo C3_8, c icloalqu (in / in) i lo C3.8-alqu (in / in) i lo C ^ -, aryl, heteroaryl, aryl-alkyl Cx.s, het eroari lo-ali lo C1-6. acyl, thioacyl, alkylsulfonyl • Cx.6, tr i f luoromet i 1 sulphi lo, ar i 1 sul fi oni lo, or heteroarylsulfonyl. • R15 VCO where V is 0 or S and R15 is alk (in / in) i lo C, cycloalk (in / in) ilo cycloalk (in / in) ilo C3.8 alk (in / in) yl C1-6, aryl, heteroaryl; or • a group R16 R17 NCO- or R16 R17 NCS- where R16 and R17, are independently, hydrogen, alk (in / in) i lo C, .6, cycloalk (en) i lo C3.8, cic loalqu (in ) i C3_8-alkyl (en / in) i lo C1.6, aryl, heteroaryl; or Rxs and R17 together with the N- atom, to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepine group; and R 2 and R 5 are independently selected from hydrogen, halogen, cyano, nitro alk (in / in) i lo r * - 1 - 6 / alkoxy alkyl 11 io hydroxy cycloalk (en) i lo C3.8, c ic loalqu ( en) i lo Cx_g, al (in / in) i lo C ^ j, alkylcarbonyl C ^ -, feni Icarboni lo, f enilcarboni the substituted halogen, trif luorme ti lo, tri f luorme ti 1 sul foni loxi and lqui lul The C1- (one of R ^ Rs being alternatively a group -NR R where R, as defined for Rx and R14, is hydrogen, alk (in / in) i lo Cx_5, c ic loalqu (in) i lo C3-8, cycloalkyl (en) i lo C3.8, alkyl (en / in) yl C1-s, aryl, heteroaryl, aryl-Cx6 alkyl or heteroaryl-Cx6 alkyl, or R13 and R14 together with the N- atom, to which they are bound, forms a group / CH2Jt where Q is C = 0, C = S or CH2; T is NH, N-alkyl, S, O or CH2 and p is 1-4, inclusive, or two adjacent groups taken from R2 R5 can join and designate a - (CH2) 3-, or -CH = CH-NH, forming a fused ring of 5 members. R6 R9 and RX1-R12 are, independently, hydrogen, halogen, cyano, nitro, alk (in / in) i lo C6, alkoxy c? - 6 alkylthio < 1-6, hydroxy, cycloalkyl (en) yl C3.8, cycloalkyl (en) i lo C3.8 alk (en / in) i lo Cx.β, aryl, heteroaryl, f-enylcarbonyl, f-enylcarbonyl substituted halogen, trifluoromethyl, or alkylsulfonyl Cx_6 or two adjacent groups taken from R6 R9 can together form a methylenedioxy group. R10, is as defined for Rx, above; with the proviso that the substituent R3 or R4 in the position 6 can not be -NR13 R14 when Y is CH2, W is a bond, n + m is 1 and the ring is linked via the position 1 -; or a pharmaceutically acceptable acid addition salt of the same.

2. The compound of claim 1, characterized in that Y is CH23.

The compound of claim 1, characterized in that Y is NR1, or complete N "a dihydroindole ring.

4. The compound of Claim 3, characterized in that Y is NR1 and that the resulting dihydroindole ring is linked to the group (CH2) n-W- (CH2) m via the 2- or 3- position.

5. The compound of claim 3, characterized in that Y is N and that the resulting dihydroindole ring is linked to the group (CH2) n-W- (CH2) ra via the 1- position.

6. The compound of claim 2, characterized in that A is a group a) linked to X via the 2 or 3 position, or a group b).

7. The compound of claim 6, characterized in that A is a group a) linked to X via position 2 or 3.

8. The compound of claim 2, characterized in that A is a group c) linked to X via the position 4, 5, 6, or 7.

9. The compound of claims 3 to 5, characterized in that A is a group a) linked to X via the 2 or 3 position or a group b).

10. The compound of claim 9 characterized in that A is a group a) linked to X via position 2 or 3.

11. The compound of claims 3 to 5, characterized in that A is a group a) linked to X via the 4, 5, 6 or 7 position.

12. The compound of claims 1 to 11, which is characterized because X is CH.

13. The compound of claims 1 to 11 characterized in that X is C.

14. The compound of claim 13, characterized in that Y is NR1 or N that completes a dihydroindole ring and A is a) linked to X via the 2 or 3 position.

15. The compound of claim 2, characterized in that indane is linked via position 2 and A is a group a) which is linked via position 3.

16. The compound of claim 2 characterized in that indane is linked via position 2 and A is a group a) which is linked via site 2.

17. The compound of claim 2 characterized in that the indane is linked via the 2-position and A is a group b).

18. The compound of claim 2 which is characterized in that indane is linked via position 1 and A is a group a) which is linked via site 2.

19. The compound of claim 2 characterized in that indane is linked via position 1 and A is a group a) which is linked via site 3.

20. The compound of claim 2, characterized in that indane is linked via position 1 and A is a group a) which is linked via site 2.

21. The compound of claim 2, characterized in that the indane is linked via position 1 and A is a group b).

22. The compound of claim 2, characterized in that the indane is attached via position 1 and A is a group c), which is linked via the position 4, 5, 6 or 7.

23. The compound of claim 4, characterized in that the dihydroindole ring is linked via position 3 and A is a group a), which is linked via position 3.

24. The compound of claim 4, characterized in that the dihydroindole ring is linked via position 3 and A is a group a), which is linked via position 2.

25. The compound of claim 4, characterized in that the dihydroindole ring is linked via the 3-position and A is a group b).

26. The compound of claim 4, characterized in that the dihydroindole ring is linked via the 3-position and A is a group c), which is linked via the 4, 5, 6 or 7 position.

27. The compound of claim 4, characterized in that the dihydroindole ring is linked via position 2 and A is a group a), which is linked via position 3.

28. The compound of claim 4, characterized in that the dihydroindole ring is linked via position 2 and A is a group a), which is linked via position 2.

29. The compound of claim 4, characterized in that the dihydroindole ring is linked via position 2 and A is a group b).

30. The compound of claim 4, characterized in that the dihydroindole ring is linked via position 2 and A is a group c), which is linked via position 4, 5, 6 or 7.

31. The compound of claim 5, characterized in that A is a group a) that is linked via position 3.

32. The compound of claim 5, characterized in that A is a group a) that is linked via position 2.

33. The compound of claim 5, characterized in that A is a group b).

34. The compound of claim 5, characterized in that A is a group c), which is linked via position 4, 5, 6 or 7.

35. The compound of claims 1 to 34, characterized in that W is a bond and m + n is from 1 to 4.

36. The compound of claims 1 to 34, characterized in that W is a bond and m + n is from 1 to 2.

37. The compound of claims 1 to 34, characterized in that W is a bond and m + n is 1.

38. The compound of claims 1 to 34, which is characterized because W is a bond and m + n is 2.

39. The compound of claims 1 to 34, which is characterized because W is a bond and m + n is from 2 to 6.

40. The compound of claims 1 to 34, which is characterized by W being a bond and m + n e s from 2 to 4.

41. The compound of claims 1 to 34, characterized in that W is a bond and m + n is from 3 to 6.

42. The compound of claims 1 to 34, characterized in that W is a bond and m + n is from 3 to 4.

43. The compound of claims 1 to 34, characterized in that W is 0.

44. The compound of claims 1 to 34, which is characterized because W is CO.

45. The compound of claims 1 to 44, characterized in that X is CH.

46. The compound of claims 1 to 44, characterized in that X is C.

47. The compound of claims 1 to 44, characterized in that X is N.

48. The compound of claims 1 to 47, characterized in that Rx is hydrogen, Cx_6 alkyl, formyl, alkylcarbonyl or C6 alkylaminocarbonyl and R2 to R5 are independently selected from hydrogen, halogen, cyano, nitro, CX alkoxy alkyl, 6, CX_6 alkylthio, hydroxy, C3.8 cycloalkyl, C3.8 cycloalkyl, Cx_g alkyl, C6_6carbonyl, phenylcarbonyl, phenylcarbonyl, substituted halogen, trifluoride, trifluoride, sulfuric acid, and alkylsulphyl being one of R 'R "alternatively a group - NR13 R14, where R13 is hydrogen, Cx_g alkyl, acyl, alkylsulfonyl Cx_2, or a group R16 R17 NCO-, where R16 is hydrogen, C1-6alkyl, cycloalkyl C3_8, C3_8 cycloalkyl C1_6 alkyl, or aryl, and, R17 is hydrogen or alkyl or RX6 and R17 together with the N- atom to which they are linked, form a pyrrolidinyl, piperidinyl or perhydroazepine group; R14 is hydrogen or Cx_6 alkyl, or R13 and R14 join to f Ormar a pyrrolidinyl, piperidinyl or perhydroazepine group or a 5 to 7 membered unsubstituted lactam ring.

49. A compound, according to the claim 48 which is characterized in that R 'R- are selected from hydrogen, halogen, cyano, methoxy, propyloxy or -NR13 R14, where R13 is formyl, acetyl, methylaminocarbonyl, methylaminothiocarbonyl, dimethylaminocarbonyl, dimethylaminothiocarbonyl, methylsulfonyl , aminocarbonyl, cyclopropylocarbonyl, methyl, pyrrolidinylcarbonyl or 4-fluorine phenylaminocarbonyl and R14 is hydrogen or Cx.6 alkyl.

50. The compound of any of claims 1 to 49, characterized in that none of R2 to R5 is a group -NR13 R14.

51. The compound of any of claims 1 to 49, characterized in that at least one of R2 to Rs is a group -NR13 R14.

52. The compound of claims 1 to 47, which is characterized in that two adjacent groups taken from R2 to Rs join and designate - (CH2) 3 or -CH = CH-NH-, forming a 5-merged ring.

53. The compound of claim 52, characterized in that two adjacent groups taken from R2 to R5 join and designate -CH = CH-NH-, forming a ring of 5 fused members.

54. The compound of claims 48-53, characterized in that R6-R9 are, independently, hydrogen, halogen, cyano, nitro, CJ.J-alkyl, C-alkoxy, C6-alkylthio, hydroxy, C3-cycloalkyl. 8, C3.8 cycloalkyl Cx_6 alkyl, aryl, heteroaryl, phenylcarbonyl, substituted phenylcarbonyl, trifluoromethyl, or C 1-6 alkylsulfonyl or two adjacent groups taken from R 6 -R 9 may be attached and designate a methylenedioxy group; R1X and R12 are hydrogen or C6 alkyl, and R10 is hydrogen, C1_s alkyl, or acyl.

55. The compound of claim 54, wherein R6 to R9 are independently selected from hydrogen, halogen, Cx_6 alkyl, C6_alkoxy, or two adjacent groups taken from R6 to R9 can be attached and designated a methylenedioxy group.

56. The compound of claim 55, wherein R9 is hydrogen.

57. The compound of claim 56, wherein R8 is hydrogen.

58. The compound of claim 57, wherein R6 to R7 are independently hydrogen or c.

59. The compound of claim 58, wherein Rs to R7 are independently hydrogen or cyclic.

60. A pharmaceutical composition characterized in that it comprises a compound of any one of Claims 1 to 59, in a therapeutically effective amount together with one or more pharmaceutically acceptable carriers or diluents.

61. Use of a compound of any one of Claims 1 to 59, for the manufacture of a medicament useful for the treatment of positive and negative symptoms of schizophrenia, other psychoses, anxiety disorders, such as generalized anxiety disorder, panic disorders and Obsessive compulsive disorder, depression, alcohol abuse, disorders to control impulses, aggression, side effects induced by conventional antipsychotic agents, ischemic pathological states, migraine, senile dementia, and cardiovascular disorders and for the improvement of sleep.