KR930004234A - 메타노안트라센 화합물 - Google Patents

메타노안트라센 화합물 Download PDF

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KR930004234A
KR930004234A KR1019920014635A KR920014635A KR930004234A KR 930004234 A KR930004234 A KR 930004234A KR 1019920014635 A KR1019920014635 A KR 1019920014635A KR 920014635 A KR920014635 A KR 920014635A KR 930004234 A KR930004234 A KR 930004234A
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pyridyl
chloro
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톰즈 제이컵스 로버트
존 온마크트 사이러스
에이미 트레이너 다이안
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수잔 제인 젠틀
임페리얼 케미칼 인더스트리스 피엘씨
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    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/10Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms
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    • C07D401/00Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
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    • C07D211/06Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D211/00Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
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    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D417/00Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms

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Abstract

내용 없음.

Description

메타노안트라센 화합물
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (10)

  1. 하기 일반식(Ⅰ)의 화합물 또는 이의 약학적으로 허용 가능한 염:
    상기식에서, X 및 Y는 수소 및 할로로부터 독립적으로 선택되고;R2는 하기 일반식 (Ia)-(Ic)로 나타낸 구조로 부터 선택된다.
    상기식에서, R3는 (3-6C)시클로 알킬;(1-6C)알킬;(1-6C)알킬, (1-6C)알콕시, 히드록시, 할로, 시아노, 니트로, 벤조일, 일반식 SO2NRaRb을 갖는 디(1-6C)알킬아미노(1-6C)알킬 아미노설포닐 및 일반식 CONRcRd를 갖는 아미노카르보닐로 구성된 군으로부터 독립적으로 선택된 0-3개의 치환체를 각각 함유하는 페닐 및 나프틸(이때, Ra, Rb, Rc및 Rd는 수소 및(1-6C)알킬로부터 독립적으로 선택되거나, 또는 Ra, Rb, Rc및 Rd각각이 결합되어 있는 질소원자와 함께 5-원 또는 6-원 헤테로시클릭 고리를 형성하며, 상기의 질소는 유일한 이종원자이다);질소, 산소 및 황으로부터 선택된 1-3개의 이종원자를 함유하고, 히드록시, (1-6C)알킬, (1-6C)알콕시, (1-6C)히드록시알킬, 페닐, 클로로 및 플루오로로부터 선택된 0-2개의 치환체를 함유할 수 있는 5-원 및 6-원 헤테로아릴고리 및 이의 벤즈 유도체로부터 선택되고;R4는 수소 및 (1-6C)알킬로부터 선택된다.
  2. 제1항에 있어서, X 및 Y는 수소 및 클로로로부터 독립적으로 선택되며, (a) R2가 상기 일반식 (Ia)일때, R3는 2-피리딜 및 3-피리딜로부터 선택되고, R4는 수소 및 메틸로부터 선택되며;(b) R2가 상기 일반식(Ib)일때, R3는 3-피리딜이며;(c) R2가 상기 일반식(Ic)일때, R3는 2-히드록시-3-피리딜이고, R4는 수소인 화합물.
  3. 하기로 구성된 군으로부터 선택된 화합물:R-1-〔((9S,10S)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-피페리딜〕-1-(3-피리딜)메탄올;S-1-〔1-((9S,10S)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-피페리딜〕-1-(3-피리딜)메탄올;(R,S)-1-〔1-9RS,10RS)-(2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-피페리딜〕-1-(3-피리딜)메탄올;1-((9S,10S)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-(2-히드록시-3-피리딜메틸)피페리딘;1-((9RS,10RS)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-(2-히드록시-3-피리딜메틸)피페리딘.
  4. 하기 일반식(Ⅰ)의 화합물 또는 이의 약학적으로 허용 가능한 염을 포함하는 약학적 조성물:
    상기식에서, X 및 Y는 수소 및 할로로부터 독립적으로 선택되고;R2는 하기 일반식 (Ia)-(Ic)로 나타낸 구조로 부터 선택된다:
    식에서, R3는 (3-6C)시클로알킬;(1-6C)알킬;(1-6C)알킬, (1-6C)알콕시, 히드록시, 할로, 시아노, 니트로, 벤조일, 일반식 SO2NRaRb을 갖는 디(1-6C)알킬아미노(1-6C)알킬 아미노설포닐 및 일반식 CONRcRd를 갖는 아미노카르보닐로 구성된 군으로부터 독립적으로 선택된 0-3개의 치환체를 각각 함유하는 페닐 및 나프틸(이때, Ra, Rb, Rc및 Rd는 수소 및(1-6C)알킬로부터 독립적으로 선택되거나, 또는 Ra, Rb, Rc및 Rd각각이 결합되어 있는 질소원자와 함께 5-원 또는 6-원 헤테로시클릭 고리를 형성하며, 상기의 질소는 유일한 이종원자이다);질소, 산소 및 황으로부터 선택된 1-3개의 이종원자를 함유하고, 히드록시, (1-6C)알킬, (1-6C)알콕시, (1-6C)히드록시알킬, 페닐, 클로로 및 플루오로로부터 선택된 0-2개의 치환체를 함유할 수 있는 5-원 및 6-웬 헤테로아릴고리 및 이의 벤즈 유도체로부터 선택되고;R4는 수소 및 (1-6C)알킬로부터 선택된다.
  5. 제4항에 있어서, X 및 Y는 수소 및 클로로로부터 독립적으로 선택되며, (a) R2가 상기 일반식 (Ia)일때, R3는 2-피리딜 및 3-피리딜로부터 선택되고, R4는 수소 및 메틸로부터 선택되며;(b) R2가 상기 일반식 (Ib)일때, R3는 3-피리딜이며;(c) R2가 상기 일반식 (Ic)일때, R3는 2-히드록시-3-피리딜이고, R4는 수소이다.
  6. 제5항에 있어서, 상기 화합물이 하기로 부터 선택된 조성물:R-1-〔1-((9S,10S)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-피페리딜〕-1-(3-피리딜)메탄올;S-1-〔1-((9S,10S)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-피페리딜〕-1-(3-피리딜)메탄올;(R,S)-1-〔1-9RS,10RS)-(2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-피페리딜〕-1-(3-피리딜)메탄올;1-((9S,10S)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-(2-히드록시-3-피리딜메틸)피페리딘;1-((9RS,10RS)-2-클로로-9,10-디히드로-9,10-메타노안트라센-9-일메틸)-4-(2-히드록시-3-피리딜메틸)피페리딘.
  7. (a) R2가 하기 일반식 (Ia)일대, 일반식(II)의 상응하는 아미드를 환원시키고;(b) R2가 하기 일반식(Ia)이고, R4가 수소일때, 하기 일반식(III)의 상응하는 알데히드를 일반식 R3Li의 사용하는 알킬리튬 화합물로 처리하고;(c) R2가 하기 일반식(Ia)이고, R4가 수소일때, 하기 일반식(III)의 상응하는 알데히드를 Z가 할로기인 일반식R3MgZ의 마그네슘 할리이드로 처리하고;(d) R2가 하기 일반식(Ia)이고, R4가 (1-6C) 알킬일때, 하기 일반식(IV)의 케톤을 Z가 할로기인 일반식R4MgZ의 상응하는 알킬마그네슘 할라이드로 처리하고;(e) R2가 하기 일반식(Ia) 이고, R4가 (1-6C)알킬일때, 하기 일반식(IV)의 케톤을 일반식 R4Li의 상응하는 알킬리튬 화합물로 처리하고;(f) R2가 하기 일반식(Ib)일때, 하기 일반식(V)의 상응하는 알콜을 산화시키고;(g) R2가 하기 일반식(Ic)일때, 하기 일반식(VI)의 상응하는 알콜을 환원시키고, 이후에, 약학적으로 허용가능한 염의 요구될때, 통상적인 방법으로 상기 화합물을 적당한 산과 반응시키는 것을 특징으로 하는 제1항 내지 제3항중 어느 한 항에서 정의된 화합물을 제조하는 방법:
    식중, X, Y, R3및 R4는 제2항에서 주어진 의미를 갖는다.
  8. X, Y, R3및 R4가 제1항에서 주어진 의미를 갖는 하기 일반식(II)의 화합물.
  9. X, Y, R3가 제1항에서 주어진 의미를 갖는 하기 일반식(V)의 화합물.
  10. X, Y, R3및 R4가 제1항에서 주어진 의미를 갖는 하기 일반식(VI)의 화합물:
    ※참고사항:최초출원 내용에 의하여 공개하는 것임.
KR1019920014635A 1991-08-15 1992-08-14 메타노안트라센 화합물 KR100233209B1 (ko)

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GB919117644A GB9117644D0 (en) 1991-08-15 1991-08-15 Amine derivatives
GB9117644.6 1992-04-07
GB929207539A GB9207539D0 (en) 1992-04-07 1992-04-07 Therapeutic agents
GB9207539.9 1992-04-07

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KR930004234A true KR930004234A (ko) 1993-03-22
KR100233209B1 KR100233209B1 (ko) 1999-12-01

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KR100233209B1 (ko) 1999-12-01
IE922587A1 (en) 1993-02-24
ES2092645T3 (es) 1996-12-01
IL102806A0 (en) 1993-01-31
FI923662A (fi) 1993-02-16
HU9202641D0 (en) 1992-10-28
CA2076168A1 (en) 1993-02-16
AU652653B2 (en) 1994-09-01
DK0532177T3 (da) 1997-03-24
TW222622B (ko) 1994-04-21
EP0532177B1 (en) 1996-10-16
DE69214586T2 (de) 1997-03-20
AU2101792A (en) 1993-02-18
DE69214586D1 (de) 1996-11-21
CZ251892A3 (en) 1993-02-17
NO923198L (no) 1993-02-16
NO923198D0 (no) 1992-08-14
HUT66623A (en) 1994-12-28
US5550136A (en) 1996-08-27
GB9216297D0 (en) 1992-09-16
US5399568A (en) 1995-03-21
JP3281047B2 (ja) 2002-05-13
EP0532177A1 (en) 1993-03-17
NZ243954A (en) 1995-09-26
GR3021399T3 (en) 1997-01-31
FI923662A0 (fi) 1992-08-14
US5719166A (en) 1998-02-17
JPH05246988A (ja) 1993-09-24
ATE144252T1 (de) 1996-11-15

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