KR900009610A - 약학적 활성을 갖는 중추 신경계 화합물 - Google Patents

약학적 활성을 갖는 중추 신경계 화합물 Download PDF

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KR900009610A
KR900009610A KR1019890018094A KR890018094A KR900009610A KR 900009610 A KR900009610 A KR 900009610A KR 1019890018094 A KR1019890018094 A KR 1019890018094A KR 890018094 A KR890018094 A KR 890018094A KR 900009610 A KR900009610 A KR 900009610A
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hydrogen
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에인 슬리 밀러 앨리스테어
스튜어트 나브즈 말콤
말틴 하이드 리챠드
존 리치 마이클
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엘. 디. 젠킨스
더 웰컴 화운데이션 리미티드
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Abstract

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Description

약학적 활성을 갖는 중추 신경계 화합물
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (21)

  1. 포유동물의 중추신경계(CNS) 장애 또는 질환을 치료하거나 예방하기 위한 약제의 제조에 있어서 일반식(Ⅰ)의 화합물 또는 그것의 산부가염의 용도.
    상기 일반식(Ⅰ)에서, R1및R2는 동일하거나 상이하고 수소, 할로, 히드록시, 알콕시, 알킬, 알킬티오 및 NR'R"기로 부터 선택되는데, NR'R"에서 R' 및 R"은 동일하거나 상이하며, 수소, 알킬, 아릴 및 아릴알킬로 부터 선택되거나 그들과 결합된 질소원자와 함께 시클릭고리를 형성하며, 상기 고리는 하나 이상의 알킬기로 임의 치환되고 헤테로원자를 임의로 더 포함하기도 하고, R3은 수소, 하나 이상의 할로라디칼에 의해 임의 치환된 알킬, 아미노, 알킬아미노, 디알킬아미노, 시아노, 니트로, 할롤, 카바모일, 히드록시, 카르복시, 알콕시, 알킬티오, 알킬티오알킬, S (0)n 알킬, 디(알킬옥시)알킬, -C(R) : NOH 또는 -COR 또는 -CO2R(R은 수소 또는 알킬), CH2X기 (X는 히드록시, 알콕시, 알릴옥시, 아릴알킬옥시, 할로, 시아노, -NR'R" (R' 및 R'은 상기 정의된 것과 동일함). S(0)n-알킬 (n은 1또는 2), 또는 S02N(R'")2(R'"은 수소 또는 알킬로 부터 선택됨)이고, R4내지 R8은 각각 동일하거나 상이하며 각각 수소, 할로, 알킬, 퍼할로알킬, 시아노, 카바모일, 카르복시, COR, 니트로, 아미노, 알킬설포닐아미노, 알콕시, S(0)n-알킬(n은 1또는2) 또는SO2N(R'")2이거나, R4와 R5또는 R5와 R6는 함께 -CH=CH-CH=CH-기 또는 -CH2-CH2-CH2-CH2- 기인데 이런 경우 R7와 R8은 둘다 수소이고, 피리미딘 고리에서 임의의 하나의 질소원자는 N-알킬화되거나 선택적으로 N-옥사이드이고, 전술한 알킬기 또는 알킬함유기의 알킬부분은 C1φ6이고, 아릴기 또는 아릴 함유기의 아릴부분은 C6φ10이다.
  2. 제1항에 있어서, R1및 R2중 하나는 아미노이고 다른 하나는 아미노, 히드록시, 할로, 모르폴리노, 피페라지닐, N-알킬피페라지닐,N,N-디알킬아미노,N-알킬아미노 또는 알킬티오로 부터 선택되고, R3는 하나이상의 할로 라디칼로 임의 치환된 알킬, 알킬티오, 수소, 히드록시, 알콕시, 할로, 카르복시, 카바모일 또는 CH2X기 (X는 히드록시, 펜옥시, 벤질옥시, 알콕시 또는 알킬티오)이고, R4와R5중 하나는 할로이고 다른 하나는 할로 또는 수소로부터 선택되고, R6는 할로, 수소, 니트로또는 아미노이고, R7은 수소, 할로, 시아노, 알킬티오, SO2N(R"')2, 알킬, 니트로, 아미노 또는 메탄설폰아미도 및 R8은 수소 또는 할로인 화합물의 용도.
  3. 제1항 또는 제2항에 있어서, R1이 히드록시아미노,N-알킬아미노,N,N-디알킬아미노, 모르폴리노, 피페라지닐,N-알킬피페라지닐인 화합물의 용도.
  4. 제1항 내지 제3항중 어느 한항에 있어서, R2가 클로로, 아미노,N,N-디알킬아미노 또는 피페리디노인 화합물의 용도.
  5. 제1항 내지 제4항중 어느 한항에 있어서, R3가 수소, 알킬, 메톡시메틸, 트리플루오로메틸, 벤질옥시 메틸, 펜옥시메틸 또는 메틸리오메틸인 화할물의 용도.
  6. 제1항 또는 제2항에 있어서, R1과 R2중 하나는 아미노이고 다른 하나는 아미노, 피페라지닐 또는N-메틸피페라지닐,N-알킬아미노,N,N-디알킬아미노이고 R3는 수소, 메틸, 트리플루오로메틸 또는 메톡시메틸인 화합물의 용도.
  7. 제1항에 있어서, R1이 아미노, 피페라지닐,N-메틸피페라지닐,N-모르폴리노,N,N-디메틸아미노, 및N-에틸아미노로 부터 선택되고, R2는 아미노이고, R3는 트리플루오로메틸, 수소, 메틸, 벤질옥시메틸, 메톡시메틸 및 메틸티오메틸로 부터 선택되고, R4는 클로로이고, R5,R6및 R7중 최소한 하나는 클로로이고 나머지는 수소, 클로로 및 니트로로 부터 선택되며, 및 R8은 수소이거나 R4와 R8이 둘다수소이고, R5와 R7이 둘다 클로로이며, R6는 수소, 클로로 및 니트로로 부터 선택되는 화합물의 용도.
  8. 제1항에 있어서, R1내지 R8은 상기 정의된 것과 같고 R7은 할로, R3는 수소, 퍼할로알킬, 메틸 또는 메톡시메틸, 및/또는 R6는 니트로, 및/또는 R1은N-알킬 피페라지닐, 모르폴리노,N,N-디메틸아미노, 피페라지닐 또는N-에틸 아미노인 것을 조건으로 하거나, R6는 클로로, R4는 할로 및 R3은 수소, 퍼할로알킬, 메톡시메틸, 메틸 또는 할로 및/또는 R1이N-메틸피페라지닐, 피페라지닐, 모르폴리노 또는N,N-디메틸아미노 또는N-에틸아미노인 것을 조건으로 하고. 포유동물의 CNS장애 또는 질환을 치료하거나 예방하기 위한 약물의 제조에 있어서 일반식(Ⅰ)의 화합물 또는 그것의 산부가염의 용도.
  9. R4내지 R8중 최소한 하나는 수소이외의 것임을 조건으로 하고 추가로 R1및 R2가 둘다 아미노이거나, R1은 히드록시, R2는 아미노, R3는 알킬 또는 수소 및 R7은 수소일때 R4및 R5둘다 할로인 것을 조건으로 하는 제1항에 정의된 일반식(Ⅰ)의 화합물 또는 그것의 산부가염.
  10. R1내지 R6그리고 R8은 제1항에 정의된 것과 같고 R7은 할로, 알킬, 퍼할로알킬, 시아노, 니트로, 아미노, 알킬티오, S(0)n-알킬 또는 SO2N(R)2인 일반식(Ⅰ)의 화합물 또는 그것의 산부가염.
  11. R2내지 R8은 제1항에 정의된 것과 같고 R1은 모르폴리노, 피페라지닐,N-알킬피페라지닐,N,N-디알킬아미노,N-알킬아미노 또는 알킬티오인 일반식(Ⅰ)의 화합물 또는 그것의 산부가염.
  12. R1및 R2는 제1항에 정의된 것과 같고, R3은 알콕시, 알킬티오 또는 하나 이상의 할로 라디칼로 치환된 알킬 또는 CH2X기(X는 알킬티오, 아릴옥시, 아릴알킬옥시, 알킬옥시 또는 히드록시임)이고, R4내지 R6는 동일하거나 상이하며 각각 수소, 할로, 퍼할로알킬, 시아노, 니트로, 아미노 또는 알킬티오로 부터 선택되고, R7은 할로, 알킬, 퍼할로알킬, 시아노, 니트로, 아미노 또는 S02N(R)2기 (R는 알킬임)이고 R8은 수소 또는 할로인 인반식(Ⅰ)의 화합물 또는 그것의 산부가염.
  13. R1,R2,R4,R5,R6,R7및 R8은 제1항에 정의된 것과 같고 R3은 알콕시, 아릴옥시, 아릴알킬옥시 또는 알킬티오인 일반식(Ⅰ)의 화합물 또는 그것의 산부가염.
  14. 4-아미노-2-(4-메틸피페라진-1-일)-5-(2,3,5-트리클로로페닐)-5-트리플루오로메틸 또는 그것의 산부가염.
  15. 2,4-디아미노-5-(2,3,5-트리클로로페닐)-6-메톡시메틸피리미딘 또는 그것의 산부가염.
  16. 4-아미노-2-(4-메틸페페라진-1-일)-5-(2,3,5-트리클로로페닐)피리미딘 또는 그것의 산부가염.
  17. 2,4-디아미노-5-(2,3,5-트리클로로페닐)-6-트리플루오로 메틸피리미딘 또는 그것의 산부가염.
  18. 2,4-디아미노-5-(4-니트로-2,3,5-트리클로로페닐)피리미딘 2,4-디아미노-5- (2,3,5-트리클로로페닐)-6-메틸피리미딘 4-아미노-2-N-모르폴리노-5-(2,3,5-트리클로로페닐)-6-트리플루오로메틸피리미딘 4-아미노-2-N,N-디메틸아미노-5-(2,3,5-트리클로로페닐)-6-트리플루오로메틸피리미딘 4-아미노-2-모르폴리노-N-5-(2,3,5-트리클로로페닐)피리미딘 4-아미노-2-N,N-디메틸아미노-5-(2,3,5-트리클로로페닐)-피리미딘 4-아미노-6-메틸-2-(4-메틸피페라진-1-일)-5-(2,3,5-트리클로로-페닐)피리미딘, 2,4-디아미노-5-(2,3-디클로로페닐)-6-트리플루오로메틸피리미딘, 2,4-디아미노-5-(2,3-디클로로페닐)-6-메틸피리미딘, 2,4-디아미노-5-(2,3-디클로로페닐)-6-메톡시 메틸피리미딘, 2,4-디아미노-5-(2,4-디클로로페닐)-6-트리플르오로메틸피 리미딘, 6-벤질옥시메틸-2,4-디아미노-5-(2,4-디클로로페닐)피리미딘, 2-N-메틸피페라지닐-4-아미노-5-(2,4-디클로로페닐)피라미딘, 2,4-디아미노-5-(2,5-디클로로페닐)-6-트리플루오로메틸피리미딘, 2,4-디아미노-5-(2,3,5-트리클로로페닐)피리미 딘, 4-아미노-5-(3,5-디클로로페닐)-6-메틸-2-(4-메틸피페라진-1-일)피리미딘, 4-아미노-2-N-에틸아미노-5-(2,3,5-트리클로페닐)피리미딘, 4-아미노-2-N-메틸아미노-5-(2,3,5-트리클로로페닐)피리미딘 또는 그들의 산부가염.
  19. 제9항 내지 제18항중 어느 한항에 의한 화합물, 이를 위한 하나 이상의 허용 담체 및 임의의 다른 치료성분을 포함하는 약학적 제제.
  20. 일반식(Ⅰ)의 화합물을 일반식(Ⅲ)의 화합물과 반응시키고 유리염기 또는 그것의 산부가염으로서 일반식(Ⅰ)의 화합물을 분리하고 선택적으로 상기 염기를 그것의 산부가염 또는 다른 산부가엽 또는 일반식(Ⅰ)의 다른 화합물 또는 그것의 산부가염으로 전환함을 포함하며 제9항 내지 제18항중 어느 한항에 의한 화합물 또는 그것의 산염을 제조하는 방법.
    상기식에서, R1과 R3내지 R8은 상기 정의한 것과 같고 L은 이탈기이며, Y는 시아노 또는 카르복시, 카르보닐 또는 악콕시 카르보닐이다.
  21. 치료시 사용되는 제9항 내지 제18항중 어느 한항에 의한 화합물 또는 그것의 약학적 허용염.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019890018094A 1988-12-07 1989-12-06 피리미딘계 화합물 및 이를 함유하는 중추신경계 질환치료용 약학 조성물 KR0145308B1 (ko)

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US2688019A (en) * 1951-08-25 1954-08-31 Burroughs Wellcome Co 6-aryl-2,4-diamino pyrimidines and process of preparing same
DE951991C (de) * 1952-01-30 1956-11-08 Rhone Poulenc Sa Verfahren zur Herstellung von neuen chlorierten Derivaten des Pyrimidins
DE956306C (de) * 1952-01-30 1957-01-17 Rhone Poulenc Sa Verfahren zur Herstellung von neuen Derivaten des Pyrimidins
GB760944A (en) * 1952-11-04 1956-11-07 Wellcome Found Improvements in and relating to pyrimidine derivatives and their manufacture
DE1009188B (de) * 1953-05-21 1957-05-29 Rhone Poulenc Sa Verfahren zur Herstellung von Pyrimidinderivaten
DE1303727B (de) * 1959-09-03 1976-02-05 Ausscheidung aus: 14 45 176 The Wellcome Foundation Ltd., London Alpha-Arylidensubstituierte Propioni-Irile
US3980781A (en) * 1966-03-31 1976-09-14 Imperial Chemical Industries Limited Fungicidal composition and method containing 2-amino-pyrimidines
DE1670854B2 (de) * 1967-04-20 1977-04-28 Bayer Ag, 5090 Leverkusen Verfahren zur herstellung von 2,4,6- trichlorpyrimidinen
US3956327A (en) * 1969-03-06 1976-05-11 Burroughs Wellcome Co. Method of preparing 2,4-diamino-5-benzyl pyrimidines
US4006235A (en) * 1973-03-23 1977-02-01 Burroughs Wellcome Co. Treating CNS lymphoma
US4005204A (en) * 1973-03-23 1977-01-25 Burroughs Wellcome Co. Treatment of neoplasms in the brain with diamino dichloroalkyl pyrimidine
US4005203A (en) * 1973-03-23 1977-01-25 Burroughs Wellcome Co. Treatment of meningeal leukemia with diamino dichlorophenyl pyrimidine
CH591457A5 (ko) * 1973-11-08 1977-09-15 Hoffmann La Roche
US3940393A (en) * 1974-06-21 1976-02-24 American Home Products Corporation Synthesis of 2,6-diaminopyrimidines
FR2306697A1 (fr) * 1975-04-10 1976-11-05 Sogeras Nouvelles pyrimidines utilisables comme medicaments antidiabetiques et hypocholesterolemiants
GB1582245A (en) * 1976-06-09 1981-01-07 Wellcome Found Benzyl cyanoacetal derivatives and their conversion to pyrimidine derivatives
DK153787C (da) * 1979-06-01 1989-01-16 Wellcome Found Analogifremgangsmaade til fremstilling af substituerede 3,5-diamino-6-phenyl-1,2,4-triaziner og alfa-cyanobenzyliden-aminoguanidinforbindelser til anvendelse som mellemprodukter herved
US4438267A (en) * 1980-11-11 1984-03-20 Daluge Susan M Monoheteroring compounds and their use
DK523781A (da) * 1980-11-27 1982-05-28 Wellcome Found Fremgangsmaade til fremstilling af benzylpyrimidiner samt mellemprodukt for disse
FR2503162A1 (fr) * 1981-04-07 1982-10-08 Pharmindustrie Nouveaux derives de piperazino-2 pyrimidine, procedes pour leur preparation et leur utilisation comme medicaments ou comme intermediaires pour la fabrication de medicaments
FR2535718A1 (fr) * 1982-11-09 1984-05-11 Sanofi Sa (piperazinyl-1)-2 pyrimidines, leurs sels, procede pour leur preparation et compositions pharmaceutiques en contenant
US4496549A (en) * 1983-01-17 1985-01-29 American Cyanamid Company Treatment of malaria with antibiotics
FR2539741A1 (fr) * 1983-01-21 1984-07-27 Sanofi Sa Composes a noyau heterocyclique diazote, leur procede de preparation et les medicaments, actifs sur le systeme nerveux central, qui en contiennent
DE3321969A1 (de) * 1983-06-18 1984-12-20 Troponwerke GmbH & Co KG, 5000 Köln 2-pyrimidinyl-1-piperazin-derivate, verfahren zu ihrer herstellung und diese enthaltende arzneimittel
DE3411571A1 (de) * 1984-03-29 1985-10-10 Merck Patent Gmbh, 6100 Darmstadt Pyrimidine
FR2567518B1 (fr) * 1984-07-11 1987-11-13 Sanofi Sa Nouveaux composes a noyau heterocyclique azote, leur preparation et les medicaments qui en contiennent
US4725600A (en) * 1984-07-13 1988-02-16 Fujisawa Pharmaceutical Co., Ltd. Pyrimidine compounds having activity as a cardiotonic anti-hypertensive cerebrovascular vasodilator and anti-platelet aggregation agent
EP0257102B1 (en) * 1986-02-24 1997-11-19 Mitsui Petrochemical Industries, Ltd. Agents for treating neurophathy
AR242678A1 (es) * 1986-03-05 1993-04-30 Gonzalez Jorge Alberto Mejoras en instrumentos musicales de cuerda de arco.
DE3620841A1 (de) * 1986-06-21 1987-12-23 Basf Ag 4-aminopyrimidinderivate
FR2602507B1 (fr) * 1986-08-08 1989-06-09 Sanofi Pharma Procede de preparation de diamino-2,4 benzyl-5 pyrimidines
PT89780A (pt) * 1988-02-23 1989-10-04 Glaxo Group Ltd Processo para a preparacao de derivados da tetrahidroisoquinolina
JPH01308229A (ja) * 1988-02-23 1989-12-12 Glaxo Group Ltd 複素環誘導体
FI895821A0 (fi) * 1988-12-07 1989-12-05 Wellcome Found Farmaceutiskt aktiva cns foereningar.
HU206337B (en) * 1988-12-29 1992-10-28 Mitsui Petrochemical Ind Process for producing pyrimidine derivatives and pharmaceutical compositions
FR2642758B1 (fr) * 1989-02-09 1991-05-17 Esteve Labor Dr Derives de pyrimidine,2-(4-((alpha)-heteroaryl-(alpha) aryl-((alpha)-alkyl)-methoxy)-butyl)-1-piperazinyl), avec activite serotoninergique
US5136080A (en) * 1989-12-04 1992-08-04 Burroughs Wellcome Co. Nitrile compounds
GB9012316D0 (en) * 1990-06-01 1990-07-18 Wellcome Found Pharmacologically active cns compounds
JPH06501926A (ja) * 1990-08-06 1994-03-03 藤沢薬品工業株式会社 複素環式化合物

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US5684005A (en) 1997-11-04
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