KR100215615B1 - 알파-옥소피롤로(2,3-b)인돌아세트산, 에스테르, 아미드 및 관련 동족체,이의 제조 방법 - Google Patents

알파-옥소피롤로(2,3-b)인돌아세트산, 에스테르, 아미드 및 관련 동족체,이의 제조 방법 Download PDF

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KR100215615B1
KR100215615B1 KR1019910007922A KR910007922A KR100215615B1 KR 100215615 B1 KR100215615 B1 KR 100215615B1 KR 1019910007922 A KR1019910007922 A KR 1019910007922A KR 910007922 A KR910007922 A KR 910007922A KR 100215615 B1 KR100215615 B1 KR 100215615B1
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lower alkyl
compounds
formula
aryl
hydrogen
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KR1019910007922A
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KR910020014A (ko
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데니스엠.플라나간
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제이 티. 쉑 2세
훽스트-러셀 파마슈티칼즈 인코포레이티드
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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

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  • Organic Chemistry (AREA)
  • Public Health (AREA)
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  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Hospice & Palliative Care (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Indole Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Steroid Compounds (AREA)

Abstract

본 발명은 일반식(I)의 화합물, 약제학적으로 허용되는 이의 산부가염, 기하 및 광학 이성체 및 이의 라세믹 혼합물에 관한 것이다.
상기식에서, X 는 -NH, 산소, N-저급알킬 또는 N-아릴저급알킬이고,
R1은 수소, 알킬, 사이클로알킬, 아릴, 아릴저급알킬, 저급알킬, 할로저급알킬, (티에닐, 푸라닐, 피콜릴 및 피리디닐로 구성되는 그룹에서 선택되는)헤테로아릴, 헤테로아릴저급알킬, (피페리디닐, 피페라지닐, 피롤리디닐로부터 선택되는)헤테로사이클릭, 또는 헤테로사이클릭저급알킬이고, R2는 수소 또는 저급알킬이고, R3은 저급알킬 또는 아릴저급알킬이고, R4는 수소, 저급알킬, 저급알케닐, 저급알키닐, 아릴저급알킬, 포밀, 저급알킬가보닐, 아릴저급알킬카보닐 또는 저급알콕시카보닐이고, Y 는 수소, 할로겐, 저급알킬 또는 저급알콕시이다.
본 발명의 화합물은 알쯔하이머 질환 등의 콜린성 결손으로 특징지워지는 다양한 기억기능장해를 완화시키는데 유용하다.

Description

α-옥소피롤로[2,3-b]인돌 아세트산, 에스테르, 아미드 및 관련 동족체, 및 이의 제조방법
본 발명은 일반식(I)의 화합물, 약제학적으로 허용되는 이의 산 부가염, 이의 기하 이성체 및 광학 이성체 및 이의 라세미체 혼합물에 관한 것이다.
1 2 3 4 1
2 2 2 2 2 2 1 2 3 4 5 5 2 6 7 2 4 2 2 4 2 4 4 -4 50 50 50 50 50 50 TM 2 4 13 17 r 2 2 4 17 22 2 3 19 26 2 3 4 3 2 4 22 24 2 3 4 4 3 2 4 23 26 2 3 4 3 2 4 18 24 2 3 4 3 2 4 22 33 3 2 4 3 2 4 23 26 2 4 4 3 2 4 23 25 2 3 4 3 2 4 21 30 2 3 4 3 4 21 30 2 3 4 3 2 4 19 27 3 2 4 3 2 4 29 42 2 10 4 3 2 4 28 40 2 10 4 3 2 4 30 39 3 10

Claims (7)

  1. 일반식(I)의 화합물, 약제학적으로 허용되는 이의 산 부가염, 이의 기하 이성체 및 광학 이성체, 및 이의 라세미체 혼합물.
    상기식에서,
    X는 O 또는 N이고,
    R1은 에틸, 디에틸, n-부틸, 페닐메틸, 페닐에틸, 이소프로필, 디이소프로필, 4-메톡시페닐메틸, 4-클로로페닐에틸, n-펜틸, n-헥실, n-옥틸 또는 n-헵틸이며,
    R2는 메틸이고,
    R3는 메틸이며,
    R4는 메틸이고,
    Y는 수소 또는 브로마이드이다.
  2. 제 1 항에 있어서, 1,2,3,3a,8,8a-헥사하이드로-α-옥소-1,3a,8-트리메틸-5-피롤로[2,3-b]인돌 아세트산, n-부틸 에스테르인 화합물.
  3. 제 1 항에 있어서, 1,2,3,3a,8,8a-헥사하이드로-α-옥소-1,3a,8-트리메틸-5-피롤로[2,3-b]인돌 아세트산, n-펜틸 에스테르인 화합물.
  4. 제 1 항에 있어서, 1,2,3,3a,8,8a-헥사하이드로-α-옥소-1,3a,8-트리메틸-5-피롤로[2,3-b]인돌 아세트산, 페닐메틸 에스테르인 화합물.
  5. 제 1 항에 있어서, 1,2,3,3a,8,8a-헥사하이드로-α-옥소-1,3a,8-트리메틸-5-피롤로[2,3-b]인돌 아세트산, 페닐에틸 에스테르인 화합물.
  6. 일반식(IV)의 화합물을 N,N,N',N'-테트라메틸에틸렌 디아민 및 2급 부틸리튬의 존재하에 일반식(Ⅶ)의 디알킬 옥살레이트와 반응시킴을 특징으로 하여, 제 1 항에 따르는 일반식(I)의 화합물을 제조하는 방법.
    상기식에서, R1, R2, R3, R4, X 및 Y는 제 1 항에서 정의한 바와 같고, R은 R1에 대한 정의와 같다.
  7. 일반식(Ⅳ)의 화합물을 에테르성 용매중의 알킬리튬 및 N', N', N', N'-테트라메틸에틸렌 디아민의 존재하에 일반식(Ⅷ)의 혼합된 옥살레이트 에스테르 아미드와 반응시킴을 특징으로 하여, 제 1 항에 따르은 일반식(I)의 화합물을 제조하는 방법.
    상기식에서,
    R1, R2, R3및 R4, X 및 Y는 제 1 항에서 정의한 바와 같고
    R6및 R7은 동일하거나 상이하며 독립적으로 에틸, 프로필 및 페닐메틸로 이루어진 그룹으로 선택되며, R은 R1에 대한 정의와 같다.
KR1019910007922A 1990-05-17 1991-05-16 알파-옥소피롤로(2,3-b)인돌아세트산, 에스테르, 아미드 및 관련 동족체,이의 제조 방법 KR100215615B1 (ko)

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KR1019990003497A KR100227715B1 (ko) 1990-05-17 1999-02-03 α-옥소피롤로[2,3-비]인돌 아세트산, 에스테르, 아미드 및 관련 동족체를 함유하는 약제학적 조성물

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US52462790A 1990-05-17 1990-05-17
US524,627 1990-05-17

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KR1019990003497A KR100227715B1 (ko) 1990-05-17 1999-02-03 α-옥소피롤로[2,3-비]인돌 아세트산, 에스테르, 아미드 및 관련 동족체를 함유하는 약제학적 조성물

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JP (1) JPH0826024B2 (ko)
KR (2) KR100215615B1 (ko)
AR (1) AR247888A1 (ko)
AT (1) ATE141273T1 (ko)
AU (1) AU634380B2 (ko)
CA (1) CA2042737A1 (ko)
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US4983616A (en) * 1990-02-01 1991-01-08 Hoechst-Roussel Pharmaceuticals Inc. Hexahydropyrrolo(2,3-B)indole carbamates, ureas, amides and related compounds
AU634654B2 (en) * 1990-05-11 1993-02-25 Hoechst-Roussel Pharmaceuticals Incorporated Pyrrolo(2,3-b)indole-ketones and analogs, a process for their preparation and their use as medicaments
MC2287A1 (fr) * 1990-06-27 1993-07-14 Hoechst Roussel Pharma Tetrahydroisoquinoleinylcarbamates de 1,2,3,3a,8,8a-hexahydro-1,31,8-trimethylpyrrolo(2,3,-b)indole
EP1283199A4 (en) 2000-05-16 2003-12-17 Takeda Chemical Industries Ltd MELANIN CONCENTRATION HORMONE ANTAGONIST
WO2010027334A1 (en) 2008-09-03 2010-03-11 Nanyang Technological University Novel tricyclic chiral compounds and their use in asymmetric catalysis

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IT1199076B (it) * 1984-03-01 1988-12-30 Consiglio Nazionale Ricerche Derivati della fisostigmina con proprieta'di inibizione della aceticolinesterasi e relativo procedimento di produzione
US4791107A (en) * 1986-07-16 1988-12-13 Hoechst-Roussel Pharmaceuticals, Inc. Memory enhancing and analgesic 1,2,3,3A,8,8A-hexahydro-3A,8 (and) 1,3A,8)-di(and tri)methylpyrrolo(2,3-B)indoles, compositions and use
US4971992A (en) * 1989-03-27 1990-11-20 Hoechst-Roussel Pharmaceuticals Inc. Carbonate derivatives of eseroline

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IL98162A (en) 1994-12-29
ZA913711B (en) 1992-01-29
ATE141273T1 (de) 1996-08-15
IE76318B1 (en) 1997-10-22
FI912363A0 (fi) 1991-05-15
GR3021043T3 (en) 1996-12-31
IL98162A0 (en) 1992-06-21
KR100227715B1 (ko) 2000-03-15
JPH04226989A (ja) 1992-08-17
FI96689C (fi) 1996-08-12
NO177710C (no) 1995-11-08
ES2094768T3 (es) 1997-02-01
AU7618291A (en) 1991-11-21
AU634380B2 (en) 1993-02-18
CA2042737A1 (en) 1991-11-18
EP0457318A1 (en) 1991-11-21
DK0457318T3 (da) 1996-12-09
JPH0826024B2 (ja) 1996-03-13
EP0457318B1 (en) 1996-08-14
AR247888A1 (es) 1995-04-28
DE69121299D1 (de) 1996-09-19
CS142991A3 (en) 1992-01-15
NO911892L (no) 1991-11-18
FI912363A (fi) 1991-11-18
HU210179B (en) 1995-02-28
NO911892D0 (no) 1991-05-15
DE69121299T2 (de) 1997-02-06
PT97688B (pt) 1998-08-31
HUT61310A (en) 1992-12-28
FI96689B (fi) 1996-04-30
PL290273A1 (en) 1992-07-27
NO177710B (no) 1995-07-31
PT97688A (pt) 1992-02-28
IE911678A1 (en) 1991-11-20
MX25777A (es) 1993-10-01
NZ238151A (ko) 1996-02-27
NZ260210A (en) 1996-02-27
CZ280922B6 (cs) 1996-05-15
HU911658D0 (en) 1991-11-28
KR910020014A (ko) 1991-12-19
MX25816A (es) 1993-11-01

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