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WO2011069294A1 - Dérivés d'adénosine à substitution n6, dérivés d'adénine à substitution n6 et leurs utilisations - Google Patents

Dérivés d'adénosine à substitution n6, dérivés d'adénine à substitution n6 et leurs utilisations Download PDF

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Publication number
WO2011069294A1
WO2011069294A1 PCT/CN2009/075478 CN2009075478W WO2011069294A1 WO 2011069294 A1 WO2011069294 A1 WO 2011069294A1 CN 2009075478 W CN2009075478 W CN 2009075478W WO 2011069294 A1 WO2011069294 A1 WO 2011069294A1
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Prior art keywords
group
substituted
unsubstituted
adenosine
alkyl
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PCT/CN2009/075478
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English (en)
Chinese (zh)
Inventor
石建功
张建军
岳正刚
李敏
朱承根
张莹
訾佳辰
王亚芳
樊晓娜
徐瑞明
林生
李燕
杨永春
盛莉
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Institute of Materia Medica of CAMS and PUMC
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Institute of Materia Medica of CAMS and PUMC
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Priority to PCT/CN2009/075478 priority Critical patent/WO2011069294A1/fr
Priority to JP2012542331A priority patent/JP2013513551A/ja
Priority to EP09851974.7A priority patent/EP2511283A4/fr
Priority to CA2783859A priority patent/CA2783859A1/fr
Priority to CN200980162826.5A priority patent/CN102812033B/zh
Priority to US13/515,152 priority patent/US10174033B2/en
Publication of WO2011069294A1 publication Critical patent/WO2011069294A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D473/00—Heterocyclic compounds containing purine ring systems
    • C07D473/26—Heterocyclic compounds containing purine ring systems with an oxygen, sulphur, or nitrogen atom directly attached in position 2 or 6, but not in both
    • C07D473/32—Nitrogen atom
    • C07D473/34—Nitrogen atom attached in position 6, e.g. adenine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/20—Hypnotics; Sedatives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
    • C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
    • C07H19/16—Purine radicals
    • C07H19/167—Purine radicals with ribosyl as the saccharide radical

Definitions

  • the present invention relates to N 6 -substituted adenosine derivatives and N 6 -substituted adenine derivatives, processes for their preparation, pharmaceutical compositions containing such compounds, and the preparation of such compounds for the preparation of sedative, hypnotic, anticonvulsant, antiepileptic
  • the application in anti-Parkinson's disease, prevention and treatment of dementia drugs and health care products belongs to the field of medical technology. Background technique
  • N 6 -substituted porphyrins and adenosine derivatives are substances with important biological activities, some of which are present in trace amounts in natural plants, as plant cytokinins promote plant cell division and differentiation, and promote seed germination. , bud differentiation, branch formation, and important biological functions such as chlorophyll and starch production, and are widely used in plant bioengineering technology research. Recent studies have found that histidine kinases, including AHK2, AHK3, and AHK4, act as receptors for cytokinins and play important roles in cytokinin signaling pathways.
  • N 6 - isopentenyl reported derivative-substituted purine derivatives is relatively large, while N 6 - isopentenyl reported derivatives substituted nucleoside derivatives less.
  • the research of such components in medical biology and its pharmacological activities is mainly focused on anti-tumor and anti-viral; at the same time, some people are deriving N 6 -phenyl substituted adenosine derivatives.
  • N 6 -(4-hydroxybenzyl)-adenosine has been isolated from Gastrodia elata, and it has been found to prevent PC12 cell apoptosis and binding to adenosine A 2A receptor, but the compound and similar components are calmed.
  • the role of central nervous system and mental system such as hypnosis has not been reported.
  • Nai-Kuei Huang, Yijuang Chern, Jim-Min Fang, Chia-ILin, Wan-PingChen, and Yun-Lian Lin Neuroprotective Principles from Gastrodiaelata, J. Nat. Prod., 2007, 70, 571-574. (and the article bow
  • a pharmaceutical composition comprising such a ⁇ 6 -substituted adenosine compound and a ⁇ 6 -substituted adenine compound is provided.
  • the use of such a ⁇ 6 -substituted adenosine compound and a ⁇ 6 -substituted adenine compound is provided.
  • the inventors of the present invention simultaneously isolated N6-(4-hydroxybenzyl group) having significant sedative and hypnotic effects from the extracts of Gastrodia elata and Ginseng ginseng by the activity tracking method in the process of studying the active ingredients of the traditional Chinese medicine Gastrodia elata and Ginseng ginseng.
  • N6-substituted adenosine and the N6-substituted adenine compound described in the present invention are as shown in the formula (VI) and esters, stereoisomers, esters, ethers and pharmaceutically acceptable salts thereof:
  • n is an integer selected from 0 to 4, preferably an integer of 1-3, more preferably an integer of 1-2
  • a linear or branched aliphatic group selected from the group consisting of hydrogen ( ⁇ ) or substituted or unsubstituted C1-6;
  • R is selected from hydrogen (H), hydroxy, substituted or unsubstituted C1-16 straight or branched fluorenyl, substituted or unsubstituted C3-8 cycloalkyl, substituted or unsubstituted phenyl (Ph) , COOR' and R' are selected from hydrogen or C1-6 alkyl.
  • COOR' is a carboxyl group (i.e., COOH); when R' is selected from a C1-6 alkyl group, COOR' is a C1-6 oxiranyl group.
  • Z is selected from the group consisting of ribosyl, esterified ribosyl, etherified ribosyl, 2'-deoxyribosyl, esterified 2'-deoxyribosyl, etherified 2'-deoxyribosyl, tetrahydrofuranyl or substituted Or an unsubstituted fat base;
  • Z is selected from the group consisting of ribose groups, esterified ribosyl groups, etherified ribose groups.
  • n is not 0, that is, an integer selected from 1-4, and neither R nor X represents hydrogen (H), the configuration of the carbon atom to which they are attached includes W type and S type or R type or S. type.
  • the group represented by I may also be selected from (5R)-5-carboxypyrrol-2-yl, (55 5-carboxypyrrol-2-yl, (5R)-5-hydroxymethylpyrrol-2-yl or (5S) a 5-hydroxymethylpyrrol-2-yl group, a substituted or unsubstituted phenyl piperazinyl group, an amino acid residue, an ester of an amino acid residue;
  • I is an amino acid residue
  • the amino acid may be any known amino acid residue, and the amino acid may be in the D configuration or the L configuration; preferably, the amino acid residue is selected from the group consisting of a phenylalanine residue, a tyrosine residue, and a tryptophan.
  • the amino acid residue COOH may form an ester with any alcohol; preferably an ester formed with an alcohol of C1-16; more preferably an ester formed with an alcohol of C1-6; most preferably a methyl ester or an ethyl ester.
  • the substituent represented may also be selected from a substituted or unsubstituted furanyl group, a substituted or unsubstituted thienyl group, a substituted or unsubstituted pyrrolyl group, a substituted or unsubstituted imidazolyl group, a substituted or unsubstituted naphthyl group, a substituted or Unsubstituted tetrahydronaphthyl, substituted or unsubstituted indenyl, substituted or unsubstituted indenyl, substituted or unsubstituted C3-8 cyclodecyl.
  • the above substituent group is selected from the group consisting of hydrazine, hydroxy (hydrazine), amino ( ⁇ 2 ), nitro ( ⁇ 0 2 ), phenyl (Ph), methylenedioxy (OCH 2 0), halogen, C1-16 , an alkyloxy group of C1-16, a thiol group of C1-16, a C1-16 decanoyl group, a C1-16 alkanoyloxy group; a fluorenyl group of the above C1-16, a decyloxy group of C1-16, C1-
  • the fluorenyl group of 16 thiol group, C1-16 decanoyl group, C1-16 decanoyloxy group may be linear or branched; substituted or unsubstituted, and further substituents are selected from the group consisting of 3 ⁇ 4, hydroxy and Amino group;
  • Preferred substituents are selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 alkoxy, C1-10 thiol, C1 -10 decanoyl, C1-10 nonanoyloxy; the above C1-10 fluorenyl group, C1-10 alkoxy group, C1-10 thiol group, C1-10 decanoyl group, C1-10 decanoyloxy group
  • the thiol group in the chain is linear or branched, substituted or unsubstituted, and Further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • substituents are selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 oxiranyl, C1-6 thiol, C1-6 Alkanoyl group, C1-6 alkanoyloxy group; the above fluorenyl group of C1-6, a fluorenyloxy group of C1-6, a thiol group of C1-6,
  • the fluorenyl group in the C1-6 decanoyl group, the C1-6 decanoyloxy group is linear or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • the most preferred substituents are selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy Base, trifluoromethyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • R is selected from hydrogen (H), hydroxy, substituted or unsubstituted C1-16 linear or branched fluorenyl, substituted or unsubstituted C3-8 cyclodecyl, substituted or unsubstituted phenyl (Ph) , COOR' and R' are selected from hydrogen or C1-6 fluorenyl; further substituents on R are preferably from hydroxy, amino, nitro, methylenedioxy, halogen; further substituents are more preferably from hydroxy, urethane Dioxy, halogen; the most preferred of the further substituents is selected from the group consisting of hydroxyl groups.
  • the parent nucleus of the compound may be attached to any suitably attached carbon atom on the furanyl group, i.e., by attachment to a carbon atom at the 2- or 3-position on the furanyl group.
  • the parent nucleus of the compound may be attached to any suitably attached carbon atom on the thienyl group, i.e., via a carbon atom at the 2- or 3-position on the thienyl group.
  • the parent nucleus of the compound may be attached to any suitably attached atom on the 2-pyrrolyl group, ie by attachment to a 2- or 3-position carbon atom on the 2-pyrrolyl group.
  • 2-pyrrolyl, 3-pyrrolyl any suitably attached atom on the 2-pyrrolyl group, ie by attachment to a 2- or 3-position carbon atom on the 2-pyrrolyl group.
  • the parent nucleus of the compound may be attached to any suitably attached atom on the naphthyl group, preferably to the carbon atom at the 1-position.
  • the parent nucleus of the compound may be bonded to any suitably bonded atom on the tetrahydronaphthyl group, preferably to the carbon atom at the 1-position.
  • the parent nucleus of the compound may be bonded to any suitably bonded atom on the fluorenyl group, preferably to the carbon atom at the 1-position, preferably to the atom at the 3-position.
  • the parent nucleus of the compound may be bonded to any suitably bonded atom on the fluorenyl group, preferably to the atom at the 9 position of hydrazine.
  • the parent nucleus of the compound can be attached to any suitably attached carbon atom on the cycloalkyl group.
  • the position of the substituent group on the substituted phenyl group includes the 2 to 6 positions of the phenyl group; the number of the substituent groups on the substituted phenyl group includes 1 to 5; methylenedioxy group (OCH 2 0 )
  • the preferred substitution position is the ortho position of the benzene ring.
  • the branched fluorenyl group comprises a saturated branched aliphatic group of 1 to 16 carbon atoms and an unsaturated branched aliphatic group; wherein the number of branches of the branched chain is 1 to 2; the unsaturated group in the long chain of the unsaturated fat Including 1 to 4 unconjugated or conjugated double bonds, also including terminal triple bonds; the esterified ribose group or 2'-deoxyribose group refers to a hydroxy group on a ribose group or a 2'-deoxyribose group. Chemical.
  • the acid used for esterification includes saturated fatty acids of 1 to 16 carbon atoms, unsaturated fatty acids (containing 1-4 unconjugated or conjugated double bonds or terminal triple bonds), phenylpropionic acid, p-toluene acrylic acid , p-hydroxyphenylpropionic acid, phenylacrylic acid, p-hydroxyphenylacrylic acid or ferulic acid;
  • the position of the esterified hydroxyl group includes the 2', 3' and 5' positions of the ribose group; 2'-deoxyribose The 3' and 5' positions of the group are simultaneously esterified or selectively monoesterified or diesterified; the etherified ribosyl or etherified 2'-deoxyribosylribidosyl or 2'-deoxyribose
  • the hydroxyl group on the group is etherified.
  • the group used for etherification includes a saturated aliphatic group of 1 to 16 carbon atoms, an unsaturated aliphatic group (containing 1-4 unconjugated or conjugated double bonds or terminal triple bonds), phenylpropyl group, P-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropanyl, nitrophenyl; etherified sites including the 2', 3' and 5' positions of the ribose group Or the 3' and 5' positions of the 2'-deoxyribosyl group are simultaneously etherified or selectively monoetherified or bisetherified; preferred compounds of formula (VI) include, but are not limited to, the compounds of formula (I)
  • R is selected from hydrogen ( ⁇ ), hydroxy, substituted or unsubstituted C1-16 straight or branched alkyl, substituted or unsubstituted C3-8 cycloalkyl, substituted or unsubstituted phenyl (Ph) , COOR' and R' are selected from hydrogen or C1-6 alkyl;
  • the group represented by I may also be selected from 5 -5-carboxypyrrol-2-yl, (;55 5-carboxypyrrol-2-yl, (5R)-5-hydroxymethylpyrrol-2-yl or (55 5 - an ester of a hydroxymethylpyrrol-2-yl group, a substituted or unsubstituted phenyl piperazinyl group, an amino acid residue, an amino acid residue;
  • the substituent represented may also be selected from a substituted or unsubstituted furanyl group, a substituted or unsubstituted thienyl group, a substituted or unsubstituted pyrrolyl group, a substituted or unsubstituted imidazolyl group, a substituted or unsubstituted naphthyl group, a substituted or An unsubstituted tetrahydronaphthyl group, a substituted or unsubstituted fluorenyl group, a substituted or
  • the above further substituent group is selected from the group consisting of hydrazine, hydroxy (hydrazine), amino ( ⁇ 2), nitro ( ⁇ 02), phenyl (Ph), methylenedioxy (OCH20), halogen, and C1-16 fluorenyl group.
  • the thiol group of the thiol group, the C1-16 alkanoyl group, the C1-16 alkanoyloxy group may be linear or branched; substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino .
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated sulfhydryl, C1-16 unsaturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • R 2 , R 3 or R 5 are independently selected from C 7-12 saturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C7-12 saturated decanoyl group, phenylpropionyl group, p-hydroxyphenylpropionyl group, p-methylphenylpropionyl group, phenylacryloyl group, p-hydroxyphenylacryloyl group, nitrobenzoyl group;
  • R2, R3 or R5 are independently selected from the group consisting of: propyl, o-nitrophenyl, C10H21, acetyl, propionyl, p-toluene acryloyl, p-methoxyphenylpropionyl, octanoyl, C
  • R2 and R3 form a propylidene group.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (A)
  • l selected from H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 alkanoyloxy group; the above fluorenyl group of C1-16, alkoxy group of C1-16, alkylthio group of C1-16, oxime of C1-16 decanoyl group, C1-16 alkanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (A) include, but are not limited to, the compounds of formula (Aa)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 oxiranyl, C1-10 thiol, C1-10 ⁇ Acyl group, C1-10 nonanoyloxy group; the above fluorenyl group of C1-10, a decyloxy group of C1-10, an alkylthio group of C1-10, a C1-10 alkanoyl group, a fluorene of C1-10 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated sulfhydryl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, c 7 -12 saturated Alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (Aa) include, but are not limited to, the compounds of formula (Aal)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 decyloxy, C1-6 alkylthio, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, a fluorenyloxy group of C1-6, a thiol group of C1-6, a fluorenyl group of C1-6 decanoyl group, and C1-6 nonanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of formula (Aa) include compounds represented by (Aa2)
  • R1 and R2 are independently selected from H, C1-6 fluorenyl, C1-6 decanoyl;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated sulfhydryl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (A) include, but are not limited to, compounds of formula (Ab)
  • Y is selected from the group consisting of hydrazine, C1-7 alkyl,
  • R2, R3 and R5 are independently selected from hydrogen, C 7 _ 12 alkyl with saturated, phenylpropyl group, propyl p-hydroxybenzoate, p-phenylpropyl, phenyl-propenyl, propenyl, p-hydroxyphenyl, nitrophenyl And a C 7 -12 saturated alkanoyl group, a phenylpropionyl group, a p-hydroxyphenylpropionyl group, a p-methylphenylpropionyl group, a phenylacryloyl group, a p-hydroxyphenylacryloyl group, a nitrobenzoyl group, and R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (Ab) include, but are not limited to, the compounds of formula (Abl)
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxy
  • the phenylacryloyl group, the nitrobenzoyl group, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include compounds represented by (B)
  • W is selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom;
  • 1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 alkoxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; the above fluorenyl group of C1-16, a decyloxy group of C1-16, a thiol group of C1-16, a C1-16 decanoyl group, a fluorene group of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated alkanoyl, C1-16 unsaturated alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (B) include, but are not limited to, compounds of formula (Ba)
  • W is selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom;
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 alkoxy, C1-10 thiol, C1-10 ⁇ Acyl group, C1-10 nonanoyloxy group; the above C1-10 alkyl group, C1-10 decyloxy group, C1-10 sulfonylthio group,
  • the fluorenyl group in the C1-10 decanoyl group, the C1-10 decanoyloxy group is linear or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated sulfhydryl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (Ba) include, but are not limited to, compounds of formula (Bal)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 alkoxy, C1-6 thiol, C1-6 alkanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, a decyloxy group of C1-6, an alkylthio group of C1-6, a fluorenyl group of C1-6 decanoyl group, and C1-6 decanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of the formula (Bal) include, but are not limited to, the compounds of the formula (Bal)
  • Rl is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of the formula (Bal) include, but are not limited to, the compounds of the formula (Bal2)
  • Rl is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of formula (Ba) include, but are not limited to, compounds of formula (Ba2)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 alkoxy, C1-6 thiol, C1-6 alkanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, a decyloxy group of C1-6, an alkylthio group of C1-6, a fluorenyl group of C1-6 decanoyl group, and C1-6 decanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of the formula (Ba2) include, but are not limited to, the compounds of the formula (Ba21)
  • Rl is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of the formula (Ba2) include, but are not limited to, the compounds of the formula (Ba22)
  • Rl is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of formula (Ba) include, but are not limited to, compounds of formula (Ba3)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 oxiranyl, C1-6 thiol, C1-6 decanoyl, C1 -6 alkanoyloxy; the above fluorenyl group of C1-6, a fluorenyloxy group of C1-6, a thiol group of C1-6, a fluorenyl group of a C1-6 alkanoyl group, and a C1-6 nonanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of the formula (Ba3) include, but are not limited to, the compounds of the formula (Ba31)
  • Rl is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of the formula (Ba3) include, but are not limited to, the compounds of the formula (Ba32)
  • Rl is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (C)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; the above fluorenyl group of C1-16, a decyloxy group of C1-16, a thiol group of C1-16, a C1-16 decanoyl group, a fluorene group of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated sulfhydryl, C1-16 unsaturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated alkanoyl, C1-16 unsaturated alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (D)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 alkyl, C1-16 decyloxy, C1-16 thiol, C1-16 alkane Acyl group, C1-16 alkanoyloxy group; alkyl group of the above C1-16, alkoxy group of C1-16, thiol group of C1-16, C1-16 decanoyl group, alkyl group of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated alkyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (E)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; the above fluorenyl group of C1-16, alkoxy group of C1-16, thiol group of C1-16, oxime of C1-16 decanoyl group, C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated alkyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated alkanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (F)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 alkyl, C1-16 decyloxy, C1-16 thiol, C1-16 alkane Acyl group, C1-16 alkanoyloxy group; the above fluorenyl group of C1-16, a decyloxy group of C1-16, a thiol group of C1-16, a C1-16 alkanoyl group, an alkane of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (G)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 alkyl, C1-16 alkoxy, C1-16 alkylthio, C1-16 alkane Acyl group, C1-16 decanoyloxy group; the above-mentioned C1-16 fluorenyl group, C1-16 decyloxy group, C1-16 thiol group, C1-16 alkanoyl group, C1-16 alkanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (H)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 alkylthio, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; the above fluorenyl group of C1-16, alkoxy group of C1-16, thiol group of C1-16, oxime of C1-16 decanoyl group, C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated alkanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (H) include, but are not limited to, compounds of formula (Ha)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 decyloxy, C1-10 alkylthio, C1-10 ⁇ Acyl group, C1-10 nonanoyloxy group; the above C1-10 alkyl group, C1-10 decyloxy group, C1-10 thiol group, C1-10 alkanoyl group, C1-10 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated sulfhydryl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, c 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of the formula (Ha) include, but are not limited to, the compounds of the formula (Hal)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 decyloxy, C1-6 alkylthio, C1-6 decanoyl, C1 -6 alkanoyloxy; the above C1-6 fluorenyl group, C1-6 alkoxy group, C1-6 thiol group, C1-6 alkanoyl group, C1-6 decanoyloxy group in the alkyl group is straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of formula (I) include compounds represented by (J)
  • W is selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 alkoxy, C1-16 thiol, C1-16 alkane Acyl group, C1-16 nonanoyloxy group; alkyl group of the above C1-16, alkoxy group of C1-16, thiol group of C1-16, oxime of C1-16 decanoyl group, C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated alkyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (J) include, but are not limited to, compounds of formula (Ja)
  • W is selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom;
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 oxiranyl, C1-10 thiol, C1-10 ⁇ Acyl group, C1-10 nonanoyloxy group; the above-mentioned C1-10 fluorenyl group, C1-10 decyloxy group, C1-10 alkylthio group, C1-10 decanoyl group, C1-10 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • Preferred compounds of formula (J) include compounds represented by (Jal )
  • W is selected from the group consisting of an oxygen atom, a sulfur atom, and a nitrogen atom;
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 oxiranyl, C1-6 thiol, C1-6 alkanoyl, C1 -6 alkanoyloxy; the above C1-6 alkyl group, C1-6 decyloxy group, C1-6 oxime thio group, C1-6 decanoyl group, C1-6 alkanoyloxy group fluorenyl group is straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (K)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; the above-mentioned C1-16 fluorenyl group, C1-16 decyloxy group, C1-16 thiol group, C1-16 decanoyl group, C1-16 alkanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated alkyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (M)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; alkyl group of the above C1-16, alkoxy group of C1-16, alkylthio group of C1-16, oxime of C1-16 decanoyl group, C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated alkyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (N)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; alkyl group of the above C1-16, alkoxy group of C1-16, alkylthio group of C1-16, C1-16 alkanoyl group, hydrazine in C1-16 alkanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (0)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; the above fluorenyl group of C1-16, a decyloxy group of C1-16, a thiol group of C1-16, a C1-16 decanoyl group, a fluorene group of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated alkyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (P)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 nonanoyloxy group; the above fluorenyl group of C1-16, a decyloxy group of C1-16, a thiol group of C1-16, a C1-16 decanoyl group, a fluorene group of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated alkyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (Q)
  • R is selected from the group consisting of Cl-4 fluorenyl, hydroxy-substituted Cl-4 fluorenyl;
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 alkoxy, C1-16 thiol, C1-16 ⁇ Acyl group, C1-16 alkanoyloxy group; alkyl group of the above C1-16, alkoxy group of C1-16, thiol group of C1-16, C1-16 decanoyl group, alkyl group of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (Q) include, but are not limited to, compounds of formula (Qa)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 oxiranyl, C1-10 thiol, C1-10 ⁇ Acyl group, C1-10 nonanoyloxy group; the above C1-10 alkyl group, C1-10 decyloxy group, C1-10 thiol group, C1-10 decanoyl group, C1-10 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, c 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (Qa) include, but are not limited to, compounds of formula (Qal)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 alkoxy, C1-6 thiol, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, C1-6 alkoxy group, C1-6 thiol group, C1-6 decanoyl group, C1-6 alkanoyloxy group fluorenyl group is straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of the formula (Qal) include, but are not limited to, the compounds of the formula (al l )
  • R1 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of the formula (Qal) include, but are not limited to, the compounds of the formula (al2)
  • R1 is selected from the group consisting of H, methyl, ethyl, propyl, isopropyl, methyloxy, ethyloxy, propyloxy, isopropyloxy, methylthio, acetoxy, propionyloxy, trifluoro Methyl, trifluoromethoxy, fluoro, chloro, bromo, methylenedioxy.
  • Preferred compounds of formula (Q) include, but are not limited to, compounds of formula (b)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 oxiranyl, C1-10 thiol, C1-10 ⁇ Acyl group, C1-10 nonanoyloxy group; above C1-10 alkyl group, C1-10 alkoxy group, C1-10 alkylthio group, C1-10 decanoyl group, C1-10 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (Qb) include, but are not limited to, compounds of formula (bl)
  • (Qbl) R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 oxiranyl, C1-6 thiol, C1-6 alkanoyl, C1 -6 alkanoyloxy; the above fluorenyl group of C1-6, a fluorenyloxy group of C1-6, a thiol group of C1-6, a fluorenyl group of C1-6 decanoyl group, and C1-6 decanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of the formula (Qb) include compounds represented by (Qb2)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 thiol, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, a fluorenyloxy group of C1-6, a thiol group of C1-6, a fluorenyl group of C1-6 decanoyl group, and C1-6 decanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of formula (Q) include, but are not limited to, compounds of formula (Qc)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-10 fluorenyl, C1-10 oxiranyl, C1-10 thiol, C1-10 ⁇ Acyl group, C1-10 nonanoyloxy group; the above-mentioned C1-10 fluorenyl group, C1-10 decyloxy group, C1-10 alkylthio group, C1-10 decanoyl group, C1-10 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, c 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (Qc) include, but are not limited to, compounds of formula (Qcl)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 oxiranyl, C1-6 thiol, C1-6 alkanoyl, C1 -6 alkanoyloxy; the above C1-6 alkyl group, C1-6 decyloxy group, C1-6 alkylthio group, C1-6 decanoyl group, C1-6 alkanoyloxy group fluorenyl group is straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of the formula (Qc) include, but are not limited to, the compounds of the formula (Qc2)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 thiol, C1-6 alkanoyl, C1 -6 alkanoyloxy; the above fluorenyl group of C1-6, a decyloxy group of C1-6, an alkylthio group of C1-6, a C1-6 alkanoyl group, and a fluorenyl group of a C1-6 decanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (R)
  • R6 and R7 are independently selected from C1-4 fluorenyl, hydroxy-substituted C1-4 fluorenyl;
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 alkyl, C1-16 decyloxy, C1-16 thiol, C1-16 alkane Acyl group, C1-16 nonanoyloxy group; alkyl group of the above C1-16, alkoxy group of C1-16, thiol group of C1-16, oxime of C1-16 decanoyl group, C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated sulfhydryl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, Phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (R) include, but are not limited to, compounds of formula (Ra)
  • R6 and R7 are independently selected from the group consisting of a hydroxyl group and a hydroxymethyl group
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 decyloxy, C1-6 thiol, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above C1-6 fluorenyl group, C1-6 alkoxy group, C1-6 thiol group, C1-6 decanoyl group, C1-6 decanoyloxy group in the alkyl group is straight Chain or branched, substituted or unsubstituted, and further substituents selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (R) include compounds represented by (Rb)
  • R6 and R7 are independently selected from hydroxy, hydroxymethyl
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 decyloxy, C1-6 alkylthio, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, C1-6 alkoxy group, C1-6 thiol group, C1-6 alkanoyl group, C1-6 alkanoyloxy group fluorenyl group is straight Chain or branched, substituted or unsubstituted, and further substituents selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 - 12 saturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (S)
  • X is selected from substituted or unsubstituted cyclohexyl, substituted or unsubstituted phenyl;
  • R1 and a substituent on the cyclohexyl group and the phenyl group are independently selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol group, C1-16 alkanoyl group, C1-16 decanoyloxy group; the above C1-16 fluorenyl group, C1-16 decyloxy group, C1-16 thiol group, C1-16 ⁇ The fluorenyl group in the acyl group, C1-16 decanoyloxy group is linear or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxyl and amino;
  • R2, R or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated sulfhydryl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated alkanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (S) include, but are not limited to, the compounds of formula (Sa)
  • Rl and n Rl ' independently selected from H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 decyloxy, C1-6 alkylthio, C1 -6 decanoyl, C1-6 nonanoyloxy; the above C1-6 fluorenyl, C1-6 decyloxy, C1-6 alkylthio, C1-6 decanoyl, C1-6 nonanoyloxy
  • the thiol group in the chain is linear or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of the formula (Sa) include, but are not limited to, the compounds of the formula (Sal)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 fluorenyl, C1-6 alkoxy, C1-6 thiol, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, a fluorenyloxy group of C1-6, a thiol group of C1-6, a fluorenyl group of C1-6 decanoyl group, and C1-6 decanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of the formula (Sa) include compounds represented by (Sa2)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 alkoxy, C1-6 thiol, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above fluorenyl group of C1-6, a fluorenyloxy group of C1-6, a thiol group of C1-6, a fluorenyl group of C1-6 decanoyl group, and C1-6 decanoyloxy group are straight Chain or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino.
  • Preferred compounds of formula (I) include, but are not limited to, compounds of formula (T)
  • Rl is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 alkyl, C1-16 decyloxy, ⁇ thio group of Cl-16, Cl-16 alkanoyl group, C1-16 decanoyloxy group; sulfhydryl group of above C1-16, decyloxy group of C1-16, alkylthio group of C1-16, C1-16 ⁇ The alkyl group in the acyl group, C1-16 alkanoyloxy group is linear or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated sulfhydryl, C1-16 unsaturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (T) include, but are not limited to, compounds of formula (Ta)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 decyloxy, C1-6 alkylthio, C1-6 decanoyl, C1 -6 ⁇ acyloxy; the above C1-6 alkyl group, C1-6 decyloxy group, C1-6 alkylthio group, C1-6 decanoyl group, C1-6 decanoyloxy group fluorenyl group is straight Chain or branched, substituted or unsubstituted, and further substituents selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 -12 saturated alkyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Alkanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (T) include, but are not limited to, compounds of formula (Tb)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, methylenedioxy, halogen, C1-6 alkyl, C1-6 decyloxy, C1-6 alkylthio, C1-6 alkanoyl, C1 -6 alkanoyloxy; the above fluorenyl group of C1-6, a decyloxy group of C1-6, a thiol group of C1-6, a fluorenyl group of C1-6 decanoyl group, C1-6 nonanoyloxy group is straight Chain or branched, substituted or unsubstituted, and further substituents selected from the group consisting of halogen, hydroxy and amino;
  • R5 is selected from the group consisting of hydrogen, C 7 - 12 saturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C 7 -12 saturated Decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (I) include, but are not limited to, the compounds of formula (U)
  • AA is an amino acid
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred AA is selected from
  • Phenylalanine, tyrosine, tryptophan, histidine, proline, valine, threonine, serine, tryptophan, glycine, prolinol, preferred compounds of formula (VI) include but not Limited to compounds shown in formula (II)
  • R1 is selected from the group consisting of H, hydroxy, amino, nitro, phenyl, methylenedioxy, halogen, C1-16 fluorenyl, C1-16 decyloxy, C1-16 thiol, C1-16 ⁇ Acyl, C1-16 alkanoyloxy; the above fluorenyl group of C1-16, a decyloxy group of C1-16, a thiol group of C1-16, a C1-16 decanoyl group, a fluorene of C1-16 decanoyloxy group a radical is straight or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R2, R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated fluorenyl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxybenzene Propylene, nitrophenyl, C1-616 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, Nitrobenzoyl, R2 and R3 may be bonded to each other to form a ring.
  • Preferred compounds of formula (VI) include, but are not limited to, compounds of formula (III)
  • n is an integer selected from 0-4,
  • X is selected from substituted or unsubstituted phenyl, substituted or unsubstituted furanyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted naphthyl, substituted or unsubstituted tetrahydro Naphthyl, substituted or unsubstituted indenyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted indenyl, substituted or unsubstituted imidazole, substituted or unsubstituted I-indole, substituted or unsubstituted a linear or branched fluorenyl group of C3-8 cyclodecyl, substituted or unsubstituted C1-16;
  • a linear or branched aliphatic group selected from the group consisting of hydrogen (hydrazine) or substituted or unsubstituted C1-6;
  • R is selected from hydrogen ( ⁇ ), hydroxy, substituted or unsubstituted C1-16 linear or branched fluorenyl, substituted or unsubstituted C3-8 cyclodecyl, substituted or unsubstituted phenyl (Ph) , COOR' and R' are selected from hydrogen or C1-6 fluorenyl;
  • the group may also be selected from (5-5-carboxypyrrol-2-yl, (55 5-carboxypyrrol-2-yl, (5R)-5-hydroxymethylpyrrol-2-yl or (55)-5 - an ester of a hydroxymethylpyrrol-2-yl group, a substituted or unsubstituted phenyl piperazinyl group, an amino acid residue, an amino acid residue;
  • the substituent represented may also be selected from a substituted or unsubstituted furanyl group, a substituted or unsubstituted thienyl group, a substituted or unsubstituted pyrrol
  • the above further substituent is selected from the group consisting of H, a hydroxyl group, an amino group, a nitro group, a phenyl group, a methylenedioxy group, a halogen, a C1-16 alkyl group, a C1-16 decyloxy group, and a C1-16 alkyl sulfide.
  • the alkyl group in the acyloxy group is linear or branched, substituted or unsubstituted, and further substituents are selected from the group consisting of halogen, hydroxy and amino;
  • R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated sulfhydryl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, phenylpropenyl, p-hydroxyphenylpropenyl , nitrophenyl, C1-16 saturated decanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl, p-hydroxyphenylacryloyl, nitro Benzoyl group.
  • Preferred compounds of formula (III) include, but are not limited to, the compounds shown by ( ⁇ )
  • R3 or R5 are independently selected from the group consisting of hydrogen, C1-16 saturated sulfhydryl, C1-16 unsaturated fluorenyl, phenylpropyl, p-hydroxyphenylpropyl, p-methylphenylpropyl, Phenylpropenyl, p-hydroxyphenylpropenyl, nitrophenyl, C1-16 saturated alkanoyl, C1-16 unsaturated decanoyl, phenylpropionyl, p-hydroxyphenylpropionyl, p-methylphenylpropionyl, phenylacryloyl , p-hydroxyphenylacryloyl, nitrobenzoyl.
  • Preferred compounds of formula (VI) include, but are not limited to, the compounds of formula (IV)
  • n is an integer selected from 0-4,
  • X is selected from substituted or unsubstituted phenyl, substituted or unsubstituted furanyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted naphthyl, substituted or unsubstituted tetrahydro Naphthyl, substituted or unsubstituted indenyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted indenyl, substituted or unsubstituted imidazole, substituted or unsubstituted I-indole, substituted or unsubstituted a linear or branched fluorenyl group of C3-8 cyclodecyl, substituted or unsubstituted C1-16;
  • a linear or branched aliphatic group selected from the group consisting of hydrogen (hydrazine) or substituted or unsubstituted C1-6;
  • R is selected from hydrogen ( ⁇ ), hydroxy, substituted or unsubstituted C1-16 linear or branched fluorenyl, substituted or unsubstituted C3-8 cyclodecyl, substituted or unsubstituted phenyl (Ph) , COOR' and R' are selected from hydrogen or C1-6 alkyl;
  • the group represented by I may also be selected from (5ii)-5-carboxypyrrol-2-yl, (55 5-carboxypyrrol-2-yl, (5-5-hydroxymethylpyrrol-2-yl or (55) a 5-hydroxymethylpyrrol-2-yl group, a substituted or unsubstituted phenyl piperazinyl group, an amino acid residue, an ester of an amino acid residue;
  • the substituent represented may also be selected from a substituted or unsubstituted furanyl group, a substituted or unsubstituted thienyl group, a substituted or unsubstituted pyrrolyl group, a substituted or unsubstituted imidazolyl group, a substituted or unsubstituted naphthyl group, a substituted or Unsubstituted tetrahydronaphthyl, substituted or unsubstituted fluorenyl, substituted or unsubstituted fluorenyl
  • n is an integer selected from 0-4,
  • X is selected from substituted or unsubstituted phenyl, substituted or unsubstituted furanyl, substituted or unsubstituted thienyl, substituted or unsubstituted pyrrolyl, substituted or unsubstituted naphthyl, substituted or unsubstituted tetrahydro Naphthyl, substituted or unsubstituted fluorenyl, substituted or unsubstituted imidazolyl, substituted or unsubstituted fluorenyl, substituted or unsubstituted imidazole, substituted or unsubstituted anthracene, substituted or unsubstituted C3- a linear or branched fluorenyl group of 8 ring fluorenyl, substituted or unsubstituted C1-16;
  • Y is selected from hydrogen (H) or a substituted or unsubstituted C1-6 linear or branched aliphatic group
  • R is selected from hydrogen (H), hydroxy, substituted or unsubstituted C1-16 straight or branched fluorenyl, substituted or unsubstituted C3-8 cyclodecyl, substituted or unsubstituted phenyl (Ph) , COOR' and R' are selected from hydrogen or C1-6 fluorenyl;
  • the group may also be selected from carboxypyrrol-2-yl, (;55 5-carboxypyrrol-2-yl, (5R)-5-hydroxymethylpyrrol-2-yl or (55)-hydroxymethylpyrrole a 2-yl, substituted or unsubstituted phenyl piperazinyl group, an amino acid residue, an ester of an amino acid residue;
  • the substituent represented may also be selected from a substituted or unsubstituted furanyl group, a substituted or unsubstituted thienyl group, a substituted or unsubstituted pyrrolyl group, a substituted or
  • the above further substituent group is selected from the group consisting of H, hydroxy (OH), amino (NH 2 ), nitro (N0 2 ), phenyl (Ph), methylenedioxy (OCH 2 0), halogen, C1- a fluorenyl group of 16 , a decyloxy group of C1-16, a thiol group of C1-16, a C1-16 decanoyl group, a C1-16 decanoyloxy group; a fluorenyl group of the above C1-16, a decyloxy group of C1-16
  • the thiol group of C1-16, the fluorenyl group of the C1-16 alkanoyl group, the C1-16 alkanoyloxy group may be linear or branched; substituted or unsubstituted, and further substituents are selected from halogen , hydroxyl and amino groups.
  • 6-chloropurine which can be passed through hypoxanthine (6-hydroxyl group) according to the method in the literature (LaMontagne and Maurice P., Journal of Heterocyclic Chemistry 1983, 20, 295).
  • 6- chloropurine riboside according to the literature can be of Medicinal Chemistry (LakshmiP.Kotra, KonstantineK Manouilov, Journal 1996 , method 39, 5202) in muscle Glycosides are synthesized by reaction with S0 2 C1 2 ; or purchased directly from reagent companies (Sigma, Aldnch, Fluka, etc.); 6-bromoindole-2'-deoxynucleosides, according to the literature (Eduardo A. Veliz, Peter A. Beal) , J. Org. Chem. 2001, 66, 8592-8598), by reaction of 3',5'-diacetyl-adenine-2'-deoxynucleoside with tert-butyl nitrite and tribromoformamidine Synthetic.
  • the second raw material for synthesizing the above compounds is an aldehyde, a ketone or an amine which can be commercially purchased.
  • the basic procedure of the first method is as follows: In the first step, various aldehyde derivatives and hydroxylamine hydrochloride are stirred in an alcohol solvent at room temperature in the presence of anhydrous sodium acetate. The reaction solvent is evaporated to dryness, dissolved or suspended with water, and extracted with ethyl acetate. In the second step, the hydrazine of the various aldehyde derivatives obtained in the first step is dissolved in an alcohol, added with Pd/C, and hydrogenated under normal pressure in the presence of concentrated hydrochloric acid; the reaction solution is filtered, and the filtrate is concentrated to obtain the corresponding amine derivative of hydrochloric acid.
  • the hydrazine of the various aldehyde derivatives obtained in the first step is dissolved in glacial acetic acid, added with zinc powder, and reduced to obtain the corresponding amine derivative.
  • the hydrochloride of the amine derivative or the amine derivative is dissolved in the alcohol, and 6-chloropurine nucleoside (or 6-chloropurine or N 9 -substituted 6-chloropurine or 3', 5' is added.
  • 6-chloropurine nucleoside or 6-chloropurine or N 9 -substituted 6-chloropurine or 3', 5' is added.
  • 6-chloropurine nucleoside or 6-chloropurine or N 9 -substituted 6-chloropurine or 3', 5' is added.
  • 6-chloropurine nucleoside or 6-chloropurine or N 9 -substituted 6-chloropurine or 3', 5' is added.
  • the basic steps of the second method are: first step, benzotriazole, benzaldehyde derivative and adenosine, heating in the presence of an anhydrous alcohol and a catalytic acid; the reaction liquid is evaporated to remove the solvent, and then recrystallized Or chromatographic separation of a white solid.
  • the white solid obtained in the first step was heated with NaBH 4 in anhydrous tetrahydrofuran. After cooling the reaction mixture to room temperature, it was poured into an ice-water mixture, neutralized with acid, and extracted with chloroform. After the chloroform layer is recovered and dissolved, the target product is obtained by recrystallization or chromatography.
  • the N 6 -substituted adenosine derivative obtained by the above procedure is prepared by reacting with an acid anhydride or an acid chloride in pyridine.
  • Monoester or diester compound, N 6 -substituted adenosine derivative reacts with 2,2-di-methoxypropionamidine in acetone to protect the 2,3-position on ribose, then catalyzed by EDCI and DMAP
  • the esterification reaction is carried out with the corresponding acid, and finally the reaction group is removed by reaction in an aqueous solution of formic acid.
  • Another object of the present invention is to provide a N 6 -substituted adenosine derivative and an N 6 -substituted adenine derivative, and a process for the preparation thereof, which comprises a therapeutically effective amount of the N 6 -substituted gland of the present invention
  • a glycoside derivative and an N 6 -substituted adenine derivative, and optionally a pharmaceutically acceptable carrier are provided.
  • the pharmaceutical carrier commonly used in the pharmaceutical field is a pharmaceutical carrier; the preparation method of the composition is a conventional pharmaceutical preparation method in the pharmaceutical field.
  • a further aspect of the invention also relates to a pharmaceutical composition
  • a pharmaceutical composition comprising a compound of the invention as an active ingredient.
  • the pharmaceutical composition can be prepared according to methods well known in the art. Any dosage form suitable for human or animal use can be prepared by combining a compound of the invention with one or more pharmaceutically acceptable solid or liquid excipients and/or adjuvants.
  • the content of the compound of the present invention is usually from 0.1 to 95% by weight.
  • the compound of the present invention or a pharmaceutical composition containing the same may be administered in a unit dosage form, which may be enterally or parenterally, such as oral, intravenous, intramuscular, subcutaneous, nasal, oral mucosa, eye, lung, and Respiratory tract, skin, vagina, rectum, etc.
  • the dosage form can be a liquid dosage form, a solid dosage form or a semi-solid dosage form.
  • Liquid dosage forms can be solutions (including true and colloidal solutions), emulsions (including o/w, w/o and double emulsions), suspensions, injections (including water injections, powder injections and infusions), eye drops Agents, nasal drops, lotions, tinctures, etc.; solid dosage forms can be tablets (including plain tablets, enteric tablets, tablets, dispersible tablets, chewable tablets, effervescent tablets, orally disintegrating tablets), capsules ( Including hard capsules, soft capsules, enteric capsules), granules, powders, pellets, dropping pills, suppositories, films, patches, gas (powder) sprays, sprays, etc.; semi-solid dosage forms can be ointments, Gel, paste, etc.
  • the compounds of the present invention can be formulated into common preparations, as sustained release preparations, controlled release preparations, targeted preparations, and various microparticle delivery systems.
  • diluents may be starch, dextrin, sucrose, glucose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, etc.
  • humectant may be water, ethanol, or different Propyl alcohol, etc.
  • the binder may be starch pulp, dextrin, syrup, honey, glucose solution, microcrystalline cellulose, gum arabic, gelatin paste, sodium carboxymethylcellulose, methylcellulose, hydroxypropylmethyl Cellulose, ethyl cellulose, acrylic resin, carbomer, polyvinylpyrrolidone, polyethylene glycol, etc.
  • disintegrant can be dry starch, microcrystalline cellulose, low
  • Tablets may also be further formulated into coated tablets such as sugar coated tablets, film coated tablets, enteric coated tablets, or bilayer tablets and multilayer tablets.
  • the active ingredient compound of the present invention may be mixed with a diluent, a glidant, and the mixture may be directly placed in a hard capsule or a soft capsule.
  • the active ingredient can also be formulated into a granule or pellet with a diluent, a binder, a disintegrant, and then placed in a hard or soft capsule.
  • the various diluents, binders, wetting agents, disintegrants, glidant varieties used to prepare the tablets of the compounds of the invention are also useful in the preparation of capsules of the compounds of the invention.
  • water, ethanol, isopropanol, propylene glycol or a mixture thereof may be used as a solvent.
  • the solubilizing agent or co-solvent may be poloxamer, lecithin, hydroxypropyl- ⁇ -cyclodextrin, etc.; pH adjusting agent may be phosphate, acetate, hydrochloric acid, sodium hydroxide, etc.; osmotic pressure regulating agent may It is sodium chloride, mannitol, glucose, phosphate, acetate, and the like.
  • mannitol, glucose or the like may also be added as a proppant.
  • coloring agents may also be added to the pharmaceutical preparations as needed.
  • the pharmaceutical or pharmaceutical composition of the present invention can be administered by any known administration method for the purpose of enhancing the therapeutic effect for the purpose of administration. Accordingly, it is another object of the present invention to provide the use of the ⁇ 6 -substituted adenosine derivatives and ⁇ 6 -substituted adenine derivatives of the present invention in the field of pharmaceuticals and health care products, particularly the ⁇ 6 -substituted adenosine of the present invention.
  • ⁇ 6 -substituted adenosine of the present invention derivatives and ⁇ 6 - substituted adenine derivatives are useful for treating sedative and hypnotic, antidepressant, anticonvulsant, antiepileptic, anti-Parkinson's disease and prevention of dementia diseases, in particular sedative-hypnotic, antidepressant, anticonvulsant, anti- Epilepsy against Parkinson's disease and drugs and health supplements for the prevention and treatment of dementia diseases.
  • the administration amount thereof can be referred to the use of the ⁇ 6 -substituted adenosine derivative and The amount of the ⁇ 6 -substituted adenine derivative to be treated; the ⁇ 6 -substituted adenosine derivative of the present invention and the ⁇ 6 -substituted adenine derivative or the composition of the present invention are used as a health supplement, or When adding a health supplement, the amount should be less than the usual amount of treatment.
  • the pharmaceutical composition of the present invention can be administered in a wide range of dosages depending on the nature and severity of the disease to be prevented or treated, the individual condition of the patient or animal, the route of administration and the dosage form, and the like.
  • a suitable daily dose of the compound of the present invention is from 0.001 to 150 mg/kg body weight, preferably from 0.1 to 100 mg/kg body weight, more preferably from 1 to 60 mg/kg body weight, most preferably from 2 to 30 mg. /Kg weight.
  • the above dosages may be administered in one dosage unit or in divided dose units depending on the clinical experience of the physician and the dosage regimen including the use of other therapeutic means.
  • the compounds or compositions of the invention may be administered alone or in combination with other therapeutic or symptomatic agents.
  • the compound of the present invention synergizes with other therapeutic agents, its dosage should be adjusted according to the actual situation. Detailed ways
  • benzaldehyde (1.08 g), hydroxylamine hydrochloride (1.29 g) and anhydrous sodium acetate (1.67 g) were weighed and dissolved in ethanol (40 mL). The reaction was stirred at room temperature for 6 h. The solvent was recovered from the reaction solution. (20 mL) was dissolved in EtOAc (EtOAc) (EtOAc)
  • benzaldehyde oxime (1.13 g) is dissolved in ethanol (40 mL), 10% Pd/C (85 mg) and concentrated hydrochloric acid (1 mL) are added, and hydrogenation is carried out at normal pressure; the reaction solution is filtered to remove Pd/C, and the filtrate is concentrated.
  • White crystal benzylamine hydrochloride (1.29 g) was obtained.
  • benzylamine hydrochloride (355 mg) was dissolved in n-propanol (40 mL), 6-chloropurine nucleoside (143 mg) and W, N-diisopropylethylamine (2 mL) , heating to 70 ° C, reaction for 8 h ; the solvent was recovered from the reaction mixture, which was separated by silica gel column chromatography eluting with chloroform-methanol (30:1) to give a colorless solid N 6 -(benzyl)-adenosine (151 Mg ) : positive ion ESIMS M/Z 358 [M + H] + ; negative ion ESIMS mlz 356 [M - H] - and 392 [M + CI]"; H NMR (300 MHz, CD 3 OD): adenosine Section 8.20 (1H, s, H-2), 8.18 (IH, brs, H-8), 5.90 (IH,
  • hydroxybenzaldehyde (2.55 g), hydroxylamine hydrochloride (2.60 g) and anhydrous sodium acetate (3.40 g) were weighed and dissolved in ethanol (80 mL). The reaction was stirred at room temperature for 6 h; Dissolve in water (40 mL) and extract with ethyl acetate
  • hydroxybenzaldehyde oxime (2.66g) is dissolved in ethanol (70mL), 10% Pd/C (300 mg) and concentrated hydrochloric acid (8mL) are added, hydrogenation at normal pressure; the reaction solution is filtered to remove Pd/C, filtrate The white crystalline hydroxybenzylamine hydrochloride (3.02 g) was obtained.
  • hydroxybenzidine hydrochloride (3.02 g) was dissolved in n-propanol (70 mL), and 6-chloropurine nucleoside (1 g) and W,N-diisopropylethylamine were added.
  • 0-hydroxybenzaldehyde oxime (1.0 g) was dissolved in EtOH (50 mL), 10% Pd/C (150 mg) and concentrated hydrochloric acid (2.8 mL) were added, and hydrogenation was carried out at normal pressure; C, the filtrate evaporated, suspended with ethyl acetate and dissolved, and filtered to give a white solid 0 - methylamine hydrochloride-hydroxybenzotriazole (l.lg).
  • 0-hydroxybenzylamine hydrochloride (223 mg) was dissolved in n-propanol (60 mL), 6-chloropurine nucleoside (200 mg) and triethylamine (3 mL) were added and heated to 70 ° C, reaction for 8h; after recovering the solvent from the reaction solution, it is separated by silica gel column chromatography, using chloroform-methanol
  • methyl benzaldehyde oxime (2.02g) is dissolved in EtOH (50mL), force!] 10% Pd/C (318mg) and concentrated hydrochloric acid (6mL), hydrogenation at normal pressure; reaction liquid filtration to remove Pd/C After the filtrate was evaporated to dryness, ethyl acetate was evaporated and evaporated to ethylamine.
  • methylbenzylamine hydrochloride (221 mg) was dissolved in n-propanol (60 mL), 6-chloropurine nucleoside (200 mg) and triethylamine (3 mL) were added and heated to 70 ° C.
  • methyl benzaldehyde oxime (1.2g) was dissolved in EtOH (50mL), 10% Pd/C (188mg) and concentrated hydrochloric acid (3.6mL) were hydrogenated at normal pressure; the reaction solution was filtered to remove Pd/C. After the filtrate was evaporated to dryness, ethyl acetate was evaporated and evaporated to ethylamine.
  • the first step product (105 mg) was placed in a 100 mL three-necked flask, NaBH 4 (46 mg) and anhydrous tetrahydrofuran (60 mL) were added, and the mixture was heated and refluxed for 8 h; the reaction solution was cooled to room temperature and poured. The mixture was poured into an ice-water mixture, neutralized with acetic acid, and extracted with chloroform.
  • chlorobenzaldehyde oxime (2.45g) was dissolved in HOAc (25mL), Zn powder (6.15g) was added, and stirred at room temperature for 6h; the reaction solution was filtered to remove excess Zn powder and ZnOAc precipitate, and the filtrate was evaporated to dry HOAc solution. A yellow oily chlorobenzylamine (1.25 g) was obtained.
  • fluorobenzaldehyde oxime (1.8g) is dissolved in HOAc (25mL), and Zn powder (5.05g) is stirred at room temperature for 6h; 6 ⁇
  • the first step weigh benzotriazole (148 mg), cyclohexylformaldehyde (168 mg) and adenosine (251 mg) in a 100 mL three-necked flask, add absolute ethanol (40 mL) and a catalytic amount of glacial acetic acid. , adding the addition funnel (with 4A molecular sieve), connected to the condenser, heating and refluxing for 14h; the reaction liquid recovers the solvent to obtain a viscous liquid, which is separated by silica gel column chromatography and eluted with chloroform-methanol (30:1 ⁇ 15:1) , 219 mg of a white solid.
  • the first step product (152 mg) was placed in a 100 mL three-necked flask, NaBH 4 (73 mg) and anhydrous tetrahydrofuran (60 mL) were added, and the mixture was heated and refluxed for 8 h; the reaction solution was cooled to room temperature and poured. The mixture was poured into an ice-water mixture, neutralized with acetic acid, and extracted with chloroform.
  • N-phenylpiperidine (681 mg) was dissolved in n-propanol (60 mL), 6-chloropurine nucleoside (300 mg) and triethylamine (4.5 mL) were added and heated to 70 ° C for 8 h; The solvent was recovered by liquid chromatography on silica gel eluting with chloroform-methanol (20:1) to give a white solid N 6 -(4-phenylpiperazinyl)-adenosine (230 mg) : positive ion ESIMS «/z 413[M + H] + and 435 [M + Na] + ; Negative ion ESIMS mlz 411 [M—H]—he mouth 447 [M+Cl]— ;]H NMR (300MHz, DMSO-c3 ⁇ 4): adenosine moiety 8.43 (IH, s, H-2), 8.27 (IH, s, H-8), 5.92 (IH, d,
  • 2-furaldehyde oxime (1.04g) was dissolved in EtOH (50mL), force! 10% Pd/C (200mg) and concentrated hydrochloric acid (4mL) Hydrogenation under normal pressure; removal of Pd/C by filtration, recovery of solvent from the filtrate, dissolution of ethyl acetate, filtration to give white solid 2-furanmethylamine hydrochloride ( 1.13 g) o.
  • Step 3 2-furanmethylamine hydrochloride ( 281 mg) was dissolved in n-propanol (60 mL), 6-chloropurine nucleoside (200 mg) and triethylamine (3 mL) were added and heated to 70 ° C for 8 h.
  • 2-thiophenecarboxaldehyde oxime (2.75 g) was dissolved in HOAc (25 mL), Zn powder (8.63 g) was added, and stirred at room temperature for 6 h; excess Zn powder and ZnOAc were removed by filtration, and the HOAc solution was evaporated to give a yellow oil.
  • 2-thienylmethylamine (1.25 g)
  • 3-methoxy-4-hydroxybenzylamine hydrochloride (3.31 g) was dissolved in n-propanol (70 mL), and 6-chloropurine nucleoside (1 g) and N N-di were added.
  • N 6 -(3-methoxy-4-hydroxybenzyl)-2',3'-0-propionyl-adenosine 200 mg obtained in the above examples, EDCI (129.8 mg), DMAP (110.2 mg) and lauric acid (99.36 mg) - and added to dry dichloromethane (20 mL), and the reaction was stirred at room temperature for 3 h; the solvent was recovered from the reaction mixture and purified by silica gel column chromatography using chloroform-methanol (100:1) Elution gave a pale yellow solid N 6 -(3-methoxy-4-lauroyloxybenzyl)-2',3'-0-propylidene-adenosyl-5'-laurate (210 mg) : positive ion ESIMS 808 [M+H] + , 830 [M+Na] + , 546 [M+K]+.
  • N 6 -(3-methoxy-4-octanoyloxybenzyl)-2',3'-0-propionyl-adenosyl-5'-octanoate is added to the aqueous formic acid solution ( 20mL, 50% V / V), the reaction was stirred for 12h at room temperature; recovery solvent by silica gel column chromatography using chloroform-methanol (50: 1 elution) to give a pale yellow solid N 6 - (3- methoxy - 4-octanoyloxybenzyl)-adenosyl-5'-octanoate (85 mg) : positive ion ESIMS w/z 656.5 [M+H] + , 678.5 [M+Na] + , 696.5 [M+K ]+.
  • N 6 -(3-methoxy-4-hydroxybenzyl) -2',3'-C»-propionyl-adenosyl-5'-n-octanoate 150 mg was added to the formic acid.
  • the aqueous solution (20 mL, 50% V/V) was stirred at room temperature for 12 h.
  • Example 28 N 6 -(3-methoxy-4-butyryloxybenzyl)-adenosyl-5'-butyrate and N 6 -(3-methoxy-4-butanoyloxy Preparation of benzyl)-adenosine
  • the reaction was stirred at room temperature for 12 h; the solvent was evaporated, and purified by silica gel column chromatography eluting with chloroform-methanol (50:1) to give N 6 -(3-methoxy-4-butanoyloxybenzyl) - adenosine-5'-butyrate (80 mg) and N 6 -(3-methoxy-4-butyryloxybenzyl)-adenosine (60 mg): ' ⁇ NMR (300 MHz, OMSO- d 6 ):
  • N 6 -(3,4-methylenedioxyphenyl)-2',3'-0-propionyl-adenosyl-5'-n-propyl ether (260 mg) was added to aqueous formic acid (20 mL). , 50% V / V), the reaction was stirred at room temperature for 12 h; the solvent was recovered to give a pale yellow crude.
  • the second step is to take N 6 -[l-(3,45-trimethoxyphenyl)ethyl] -2',3'- ⁇ 9-propionyl-adenosyl-5'-p-methoxyphenylpropionic acid
  • the ester 160 mg was added to a formic acid aqueous solution (20 mL, 50 V/V), and the mixture was stirred at room temperature for 12h.
  • a formic acid aqueous solution 20 mL, 50% V/V
  • N 5 -[(S)-1-(phenyl)-propyl]-2',3'-0-propylidene-adenosine (330 mg) and p-toluene acrylate (150 mg), EDCI (297.40 mg) and DMAP (236.90 mg) were added to dry dichloromethane (15 mL), and stirred at room temperature for 4 h; distilled water (30 mL) was added to the reaction mixture and extracted with dichloromethane (3 ⁇ 30 mL); the chloroform phase was dried over anhydrous sodium sulfate, filtered, concentrated and purified by silica gel column chromatography using chloroform-methanol: ethyl (2001), to give a pale yellow solid N 6 - [(S) -1- ( phenyl) -propyl]-2',3'-0-propane-adenosyl-5'-p-toluene acrylate (235 mg).
  • ⁇ 6 -[(5)-1-(phenyl)-propyl]-2',3'-0-propylidene-adenosyl-5'-p-toluene acrylate 230 mg was added to The aqueous solution of formic acid (20 mL, 50% V/V) was stirred at room temperature for 12 h.
  • N 6 -[(1R)-1-(phenyl)-propyl]-2',3'- ⁇ 9-propionyl-adenosine (500.0 mg) obtained in the above examples was added to dryness.
  • THF 40 mL
  • NaH 500.0 mg
  • N 6 -[(1R)-1-(phenyl)-propyl]-2',3'- ⁇ 9-propionyl-adenosine 500.0 mg was added to dry THF (40 ml). After being completely dissolved, NaH (500.0 mg) was slowly added at room temperature, and reacted at room temperature for 2 h; n-propyl iodide (699.1 mg) was added to dry THF (10 mL), and the reaction mixture was added dropwise with a separating funnel at room temperature.
  • 1-(4-methoxyphenyl)-butanone oxime 870mg was dissolved in EtOH (50mL), 10% Pd/C (95mg) and concentrated hydrochloric acid (2.38mL), atmospheric pressure Hydrogenation; the reaction mixture was filtered to remove Pd/C, and the solvent was evaporated, and the mixture was evaporated to ethyl ether, and filtered to give a white solid, 1-(4-methoxyphenyl)-butylamine hydrochloride (965 mg).
  • 1,2-diphenylethanone oxime (5.39g) is dissolved in EtOH (50mL), force! ] 10% Pd/C (541mg) and concentrated hydrochloric acid (13.47mL), hydrogenation at atmospheric pressure; the reaction solution was filtered to remove Pd/C, and the filtrate was recovered, dissolved in ethyl acetate and filtered to obtain white solid 1-(1) , 2-diphenyl)-ethylamine (5.9 g).
  • diphenylmethylamine hydrochloride (583 mg) was dissolved in n-propanol (60 mL), 6-chloropurine nucleoside (200 mg) and triethylamine (9 mL) were added and heated to 70 ° C.
  • 6-methoxy-1,2,3,4-tetrahydronaphthalen-1-one oxime (1.87g) was dissolved in EtOH (50mL), 10% Pd/C (150mg) and concentrated hydrochloric acid (4mL), hydrogenation at atmospheric pressure; the reaction solution was filtered to remove Pd/C, and the filtrate was recovered. The solvent was dissolved in ethyl acetate and filtered to give 6-methoxy-1,2,3,4-tetrahydronaphthalene as white solid.
  • 1-amine hydrochloride (2.13 g).
  • D-phenylalanine (231 mg) was dissolved in a mixed solvent of 1,4-dioxane and water (1:1, 6 mL), and 6-chloropurine nucleoside (200 mg) and K 2 C0 3 (192 mg) were added.
  • D-tyrosine ethyl ester hydrochloride (686 mg) was dissolved in n-propanol (50 mL), 6-chloropurine nucleoside (200 mg) and triethylamine (3 mL) were added and heated to 80 ° C for 10 h.

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Abstract

La présente invention concerne des dérivés d'adénosine à substitution N6, des dérivés d'adénine à substitution N6, leurs procédés de fabrication, une composition pharmaceutique comprenant lesdits composés ci-dessus, et les utilisations de ces composés dans la fabrication de médicaments et de produits de santé pour la sédation, l'hypnose, contre les convulsions, contre l'épilepsie, contre la maladie de Parkinson, pour la prévention et le traitement de la démence.
PCT/CN2009/075478 2009-12-10 2009-12-10 Dérivés d'adénosine à substitution n6, dérivés d'adénine à substitution n6 et leurs utilisations Ceased WO2011069294A1 (fr)

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PCT/CN2009/075478 WO2011069294A1 (fr) 2009-12-10 2009-12-10 Dérivés d'adénosine à substitution n6, dérivés d'adénine à substitution n6 et leurs utilisations
JP2012542331A JP2013513551A (ja) 2009-12-10 2009-12-10 Ｎ６−置換アデノシン誘導体とｎ６−置換アデニン誘導体の鎮静、催眠，抗うつ，抗痙攣，抗てんかん，抗パーキンソン病と認知証予防・治療の用途
EP09851974.7A EP2511283A4 (fr) 2009-12-10 2009-12-10 Dérivés d'adénosine à substitution n6, dérivés d'adénine à substitution n6 et leurs utilisations
CA2783859A CA2783859A1 (fr) 2009-12-10 2009-12-10 Derives d'adenosine a substitution n6, derives d'adenine a substitution n6 et leurs utilisations
CN200980162826.5A CN102812033B (zh) 2009-12-10 2009-12-10 N6-取代腺苷衍生物和n6-取代腺嘌呤衍生物及其用途
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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002018404A2 (fr) * 2000-08-30 2002-03-07 F. Hoffmann-La Roche Ag Derives de nucleosides
WO2004058791A2 (fr) 2002-12-30 2004-07-15 Ustav Experimentalni Botaniky Akademie Ved Ceske Republiky Derives de substitution de n6-benzyle adenosine, methodes de preparation associees, leur utilisation pour realiser des medicaments, des preparations cosmetiques et des regulateurs de croissance ; preparations pharmaceutiques, cosmetiques et regulateurs de croissance contenant ces composes
CN1217952C (zh) * 1997-11-08 2005-09-07 葛兰素集团有限公司 化合物

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL128629C (fr) * 1966-05-07
NL130136C (fr) * 1966-10-20
DE1962387C2 (de) * 1969-12-12 1983-08-25 Schering AG, 1000 Berlin und 4709 Bergkamen N↑6↑-(3-Chlorbuten(2)-yl)-adenosin
US4593019A (en) * 1984-10-26 1986-06-03 Warner-Lambert Company N6 -tricyclic adenosines
WO2005069865A2 (fr) * 2004-01-13 2005-08-04 Ambit Biosciences Corporation Derives de pyrrolopyrimidine et analogues et utilisation dans le traitement et la prevention de maladies
US20080221060A1 (en) * 2004-03-05 2008-09-11 Martyn Pritchard Therapeutic Compounds
US20120295863A1 (en) 2009-11-13 2012-11-22 Yun-Lian Lin Dual-Action Compounds Targeting Adenosine A2A Receptor and Adenosine Transporter for Prevention and Treatment of Neurodegenerative Diseases

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1217952C (zh) * 1997-11-08 2005-09-07 葛兰素集团有限公司 化合物
WO2002018404A2 (fr) * 2000-08-30 2002-03-07 F. Hoffmann-La Roche Ag Derives de nucleosides
WO2004058791A2 (fr) 2002-12-30 2004-07-15 Ustav Experimentalni Botaniky Akademie Ved Ceske Republiky Derives de substitution de n6-benzyle adenosine, methodes de preparation associees, leur utilisation pour realiser des medicaments, des preparations cosmetiques et des regulateurs de croissance ; preparations pharmaceutiques, cosmetiques et regulateurs de croissance contenant ces composes

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
KAREL DOLEZAL; IGOR POPA; EVA HAUSEROVA; LUKAS SPICHAL; KUHELI CHAKRABARTY; ONDREJ NOVAK; VLADIMIR KRYSTOF; JIRI VOLLER; JAN HOLUB: "Preparation, biological activity and endogenous occurrence of N 6-benzyladenosines", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 15, 2007, pages 3737 - 3747
LAKSHMIP.KOTRA; KONSTANTINEK.MANOUILOV, JOURNAL OF MEDICINAL CHEMISTRY, vol. 39, 1996, pages 5202
LAMONTAGNE; MAURICE P., JOURNAL OF HETEROCYCLIC CHEMISTRY, vol. 20, 1983, pages 295
MADAN M. KWATRA; EDWARD LEUNG; M. MARLENE HOSEY; RICHARD D. DREEN, N 6-PHENYLADENOSINES: PRONOUNCED EFFECT OF PHENYL SUBSTITUENTS ON AFFINITY FOR A2 ADENOSINE RECEPTORS, vol. 30, 1987, pages 954 - 956
NAI-KUEI HUANG; YIJUANG CHERN; JIM-MIN FANG; CHIA-I LIN; WANG-PING CHEN; YUN-LIAN LIN: "Neuroprotective Principles from Gastrodia elata", J. NAT. PROD., vol. 70, 2007, pages 571 - 574
See also references of EP2511283A4 *

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US10479803B2 (en) 2014-06-11 2019-11-19 Incyte Corporation Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors
US10077277B2 (en) 2014-06-11 2018-09-18 Incyte Corporation Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors
US11999751B2 (en) 2014-06-11 2024-06-04 Incyte Corporation Bicyclic heteroarylaminoalkyl phenyl derivatives as PI3K inhibitors
TWI650328B (zh) * 2014-11-11 2019-02-11 中央研究院 用於預防及治療神經退化疾病及疼痛之化合物
TWI668007B (zh) * 2014-11-11 2019-08-11 中央研究院 用於預防及治療神經退化疾病及疼痛之化合物
US11084822B2 (en) 2015-02-27 2021-08-10 Incyte Corporation Salts and processes of preparing a PI3K inhibitor
US12024522B2 (en) 2015-02-27 2024-07-02 Incyte Corporation Salts and processes of preparing a PI3K inhibitor
US10336759B2 (en) 2015-02-27 2019-07-02 Incyte Corporation Salts and processes of preparing a PI3K inhibitor
US10125150B2 (en) 2015-05-11 2018-11-13 Incyte Corporation Crystalline forms of a PI3K inhibitor
US9988401B2 (en) 2015-05-11 2018-06-05 Incyte Corporation Crystalline forms of a PI3K inhibitor
US9732097B2 (en) 2015-05-11 2017-08-15 Incyte Corporation Process for the synthesis of a phosphoinositide 3-kinase inhibitor
US11414419B2 (en) 2017-06-21 2022-08-16 Mitokinin, Inc. Substituted purines for the treatment of neurodegenerative and mitochondrial diseases
US12226418B2 (en) 2018-06-01 2025-02-18 Incyte Corporation Dosing regimen for the treatment of PI3K related disorders
CN117338801A (zh) * 2023-11-13 2024-01-05 河北医科大学 N6-取代腺苷衍生物或n6-取代嘌呤衍生物在制备减轻围术期神经炎症药品中的应用
CN117338801B (zh) * 2023-11-13 2024-06-21 河北医科大学 N6-取代腺苷衍生物或n6-取代嘌呤衍生物在制备减轻围术期神经炎症药品中的应用

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EP2511283A1 (fr) 2012-10-17
CN102812033A (zh) 2012-12-05
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