KR900017994A - 사이클로알킬-치환된 글루타르아미드 이뇨제 - Google Patents

사이클로알킬-치환된 글루타르아미드 이뇨제 Download PDF

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KR900017994A
KR900017994A KR1019890007117A KR890007117A KR900017994A KR 900017994 A KR900017994 A KR 900017994A KR 1019890007117 A KR1019890007117 A KR 1019890007117A KR 890007117 A KR890007117 A KR 890007117A KR 900017994 A KR900017994 A KR 900017994A
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cis
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carbamoyl
cyclopentyl
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제임스 케이스
크리스토퍼 대닐레위츠 존
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데이비드 죤 우드
화이자 인코포레이티드
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Abstract

내용 없음

Description

사이킬로알킬-치환된 글루타르아미드 이뇨제
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (12)

  1. 일반식(Ⅰ)의 화합물 및 약제학적으로 허용된 이의 염 및 이의 생물학적 선구물질,
    상기식에서, A는 포화 또는 일-불포화일 수 있으며 임의로 추가의 포화된 5-또는 6원 카보사이크릭 환으로 융합될 수 있는 4 내지 7원 카보사이클릭 환을 완성하며:B는 (CH2)m(여기에서, m은 1 내지 3의 정수이다)이고: R 및 R4는 각각 독립적으로 H, C1-C6알킬, 벨질 또는 다른 생물학적으로 불안정한 에스테르- 형성 그룹이며; R1은 H또는 C1-C4알칼이고: R2및 R3는 각각 독립적으로 H,OH,C1-C6알킬 또는 C1-F6알콕시이거나, R2및 R3함께 연결되어 (CH2)r (여기에서, r는 1 내지 4의 정수이다)이며: Y는 적쇄 또는 측쇄일 수 있는 탄소수 1 내지 6의 임의의 알킬렌 그룹이고: R5는 R6SO2NR9-, R6SO2NR9-, R6CO2-, R6CO-, R6CO-, R6SOg-, R7NR|9CO-, R7NR9SO2- 또는 R7OCO-이며:R6는 다음 일반식의 그룹이며:은 다음 일반식의 그룹이고:은 H, C1-C6알킬, 아릴, C3-C7사이클로알킬, 헤테로사이클릴, 아릴 (C1-C6알킬) 또는 헤테로사이클릴(C1-C5알킬)이며; R8은 R4CONR4-, R9CONR4-, R13R14N-(CH|2)p또는 R9O- (여기에서, R9은 상기 정의한 바와 같다)이고; R10및 R11은 각각 독립적으로 H 또는 C1-C6알킬이거나; R10은 H이고 R11은 OH,SH,SCH3,NH2, 아릴(C1-C5알킬) OCONH-, NH2CO-, CO2H, 구아니디노, 아릴, 또는 헤테로사이클로 치환된 C1-C6알킬이거나: 두 그룹 R10및 R11은 이들이 결환된 탄소원자와 함께 포화 또는 일-불포화일 수 있으며 임의로 C1-C4알킬로 치환되거나 추가의 5 또는 6원 포화 또는불포화 카보사이클릭환으로 융합 될 수 있는 5 또는 6원 카보사이클릭환을 형성하거나:R10은 H이고, n은 0이며 R8및 R11이 연결되어 2-(N-COR9-4-아미노피롤리디닐)그룹을 형성하며:R12는R13R14NCO-, R9OCH2- 또는 헤테로사이클릴(여기에서, R9은 상기 정의 한 바와 같다)이고;R13및R14은 서로 독립적으로 H,C1-C6알킬, C3-C7사이클로알킬, 아릴, 아릴(C1-C6알킬), C2-C|6알콕시아킬, 아미노(C1-C6알킬), C2-C6알콕시알킬, 아미노(C1-C6알킬), 헤테로사이 클릴 또는 헤테로사이클릴(C|1-C6알킬)이거나; 두 그룹 R13및 R14은 이들이 결합된 질소원자와 함께 피톨리디닐, 피페리디노, 모르폴리노, 피페라지닐, N-(C1-C4알킬)피페라지닐, 피롤릴, 이미다졸릴, 피라졸릴 또는 트리아졸릴 그룹을 형성하며; n은 0 또는 1이고;P는 0또는 1 내지 6의, 정수이며; g는 0,1 또는 2이다.
  2. 제1항에 있어서, A가 (CH2)4이고, R1이 H이며 B가 (CH2)2인 일반식(Ⅱ)의 화합물.
  3. 제1항 또는 2항에 있어서, R 및 R4가 둘 모두 H인 화합물.
  4. 제1항 또는 2항에 있어서, R과 R4중 하나는 H이고 나머지 하나는 C1-C6알킬, 벤질 또는 다른 생물학적으로 불안정한 에스테르-형성 그룹인 화합물.
  5. 제4항에 있어서, 다른 생물학적으로 불안정한 에스테르 형성 그룹이 1-(2,2-디에틸부티릴옥시)에틸, 2-에틸프로피오닐옥시메틸, 1-(2-에틸프로피오닐옥시)에틸, 1-(2,4-디메텔벤조일옥시)에틸, α-벤조일옥시벤질, 1-(벤조일옥시)에틸, 2-메틸-1-프로피오닐옥시-프로필, 2,4,6-트리메틸벤조일옥시메틸, 1-(2,4,6-트리메틸벤조일옥시)에틸, 피발로일옥시메틸, 펜에틸, 펜프로필, 2,2,2-트리풀루오로에틸, 1-또는 2-나프틸, 2,4-디메틸페닐, 4-3급-부틸페닐, 5-(4-메틸-1,3-디옥살리닐-2-오닐)메틸 또는 5-인다닐인화합물.
  6. 제1항 내지 5항 중 어느 한 항에 있어서, R5가 R5CONR9-, 또는 R7NR|9CO-(여기에서, R6,R7및 R9은 상기 정의한 바와 같다)인 화합물.
  7. 제6항에 있어서, R5가 R5CONR9-이고, R9이 H이며, R6가 다음 일반시의 그룹인 화합물.
    상기식에서, R8은 (C1-C4알킬) CONH-, 아릴 CONH 또는 (C1-C|4알킬)SO2NH-이고, R10은 H이며 R11은 C1-C4알킬, 벤질 또는 아미노(C1-C|4알킬)이다.
  8. 제6항에 있어서, R5가 R7NR9CO-[여기에서, R9은 H이고 R7은 일반식 R12-- (여기에서, R12는 NO2C, (C1-C6알킬)NHCO-, (C1-C|5알킬)2NCO-, 아릴 NHCO- 또는 1-피롤리디노일이고, R10은 H이며 R11은 벤질 또는 아미노(C1-C|6알킬)이다)이다]인 화합물.
  9. 제7항에 있어서, R5가 N2-아세틸-L-리실-아미노, N2-벤조일-L-리실-아미노, N2-나프토일-L-리실-아미노, 또는-N2-메탄설폰아미도-L-리실-이미노인 화합물.
  10. 제7항에 있어서, 화합물이 2-(N2-아세틸-L-리실아미노메틸)-3-{1-{(시스)-4-카복시-사이클로헥실)카바모일]사이클로펜틸)ㅡ프로파노산, 2-(N2-벤조일-L-리실아미노메닐)-3-｛1-[(시스-4-카복시-사이클로헥실｝카바모일]사이클로펜틸)프로파노산, 2-(N2-나프토일-L-리실아미노메틸)-3-｛1-[시스-4-카복시-사이클로헥실)카바모일]사이클로펜틸)프로파노산, 2-(N2-아세틸-L-리실아미노메틸)-3-｛1-[시스-4-카복시-시스-3-부틸-사이클로헥실)카바모일]사이클로펜틸｝프로파노산, 2-(N2-나프토일-L-리실아미노메틸)-3-{1-[시스-4-카복시-사이클로펙실)카바모일]사이클로펜틸)프로파노산, 2-(N1-아세틸-L-리실아미노메틸)-3-{1-[(시스)-4-카복시-트란스-3-부틸-사이클로헥실)카바모일]사이클로펜틸}프로파노산, 2-(N2-메탄설포닐-L-리실아미노메틸)-3-{1-[시스-4-카복시-시스-3-(메틸부틸)-사이클로헥실)카바모일]사이크로펜틸)프로파노산, 또는 2-(N2-메틴설포닐-L-리시아미노메틸)-3-{1-[시스-4-카복시-시스-3-부틸-사이클로헥실)카바모일]사이클로펜틸}프로파노산인 화합물.
  11. 제1항 내지 10항 중 어느 한 항에서 청구한 일반식(Ⅰ) 또는 (Ⅱ)의 화합물 또는 약제학적으로 허용되는 이의 염 또는 이의 생물학적 선구물질과 함께 약제학적으로 허용되는 희석제 또는 담체를 함유하는 약제학적 조성물.
  12. 약제, 특히 고혈압, 심부전증 또는 신부전증 치료용 약제로 사용하기 위한 제1항 내지 10항중 어느 한 항에서 청구한 일반식(Ⅰ) 또는 (Ⅱ)의 화합물 또는 약제학적으로 허용되는 이의 염 또는 이의 선구물질.
    ※ 참고사항 : 최초출원내용에 의하여 공개하는 것임.
KR1019890007117A 1988-05-27 1989-05-27 사이클로알킬-치환된 글루타르아미드 이뇨제 KR900017994A (ko)

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AU1870292A (en) * 1991-04-16 1992-11-17 Schering Corporation Use of neutral endopeptidase inhibitors in the treatment of nephrotoxicity
US5298492A (en) * 1992-08-04 1994-03-29 Schering Corporation Diamino acid derivatives as antihypertensives
US5208236A (en) * 1992-09-23 1993-05-04 Schering Corporation N-(acylaminomethyl)glutaryl amino acids and use
US6645939B1 (en) 1997-11-24 2003-11-11 Merck & Co., Inc. Substituted β-alanine derivatives as cell adhesion inhibitors
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US7899527B2 (en) * 2004-05-13 2011-03-01 Palo Alto Investors Treatment of conditions through modulation of the autonomic nervous system during at least one predetermined menstrual cycle phase
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