KR900701759A - 비-펩타이드 레닌 억제제 - Google Patents

비-펩타이드 레닌 억제제

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KR900701759A
KR900701759A KR1019900701155A KR900701155A KR900701759A KR 900701759 A KR900701759 A KR 900701759A KR 1019900701155 A KR1019900701155 A KR 1019900701155A KR 900701155 A KR900701155 A KR 900701155A KR 900701759 A KR900701759 A KR 900701759A
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lower alkyl
heterocyclic
alkyl
amino
alkoxy
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KR1019900701155A
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케이. 엘. 펑 안토니
아르. 베이커 윌리암
아미거 요크-린
에이치. 로젠버그 사울
데 비스와내트
제이. 플라트너 제이콥
에이. 보이드 스티븐
제이. 켐프 데일
로우잉 샴 힝
디. 클라이너트 홀리스
에이. 맨타이 로버트
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폴 이. 로지
에보트 레보러토리즈
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Publication of KR900701759A publication Critical patent/KR900701759A/ko

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Abstract

내용 없음

Description

비-펩타이드 레닌 억제제
내용없음

Claims (20)

  1. 하기 일반식(I)의 화합물, 또는 약학적으로 혀용되는 염, 에스테르 또는 이의 예비약제.
    상기식에서, A는 R5C(O)-(CH2)w-(여기에서 W는 0내지4이고 R5는 하이드록시, 알콕시, 티오알콕시, 아미노 또는 치환된 아미노이다); 알킬설포닐, (아릴)설포닐 또는 (헤테로사이클릭)설포닐; 아릴, 아릴알킬, 헤테로사이클릭 또는 (헤테로사이클릭)알킬; 또는 R90-또는 R90NHC(O)-(여기에서, R90은 카복시, 알콕시카보닐, 알킬설포닐, 아릴, 아릴설포닐, 헤테로사이클릭 또는 (헤테로사이클릭)설포닐중에서 선택된 치환체로 치환된 C1내지 C4의 직쇄 또는 측쇄이다)이고, R1은 수소; 저급알킬; 저급알케닐; 사이클로 알킬알킬; 사이클로 알케닐 알킬; 아릴옥시 알킬; 티오아릴옥시 알킬; 아릴알콕시 알킬; 아릴티오 알콕시 알킬; 또는 알콕시, 티오 알콕시, 아릴및 헤테로 사이클릭 중에서 선택된 치환체로 치환된 C1내지 C3의 직쇄 또는 측쇄이고, X는 CH2,CHOH, C(O), NH, O, S, S(O), SO2, N(O) 또는 -P(O)O-이고, R3는 저급알킬, 할로알킬, 저급알케닐, 사이클로알킬알킬, 사이클로알케닐알킬, 알콕시알킬, 티오알콕시알킬, (알콕시알콕시)알킬, 하이드록시알킬, -(CH2)eeNHR12(여기에서, ee는 1내지 3이고, R12는 수소, 저급알킬 또는 N-보호 그룹이다). 아릴알킬 또는 (헤테로사이클릭)알킬이고, T는 안지오텐시노겐(angiotensinogen)의 Leu-Val분배 부위의 의태이다.
  2. 제1항에 있어서, R1은 저급알킬, 벤질 또는 펜에틸이고; X는 산소 또는 NH이고; R3는 저급알킬이고; T는이고, R4는 저급알킬 또는 사이클로알킬메틸이고; D는(여기에서, R73은 저급알킬이다),〔여기에서, M은 산소, 황 또는 NH이고; Q는 산소 또는 황이고; E는 산소, 황, CHR73(R73은 저급알킬이다), C=CH2또는 NR18(R18은 수소, 저급알킬, 하이드록시알킬, 하이드록시, 알콕시, 아미노 또는 알킬아미노이다)이고; G는 없거나 CH2또는 NR19(R19는 수소 또는 저급알킬이다)이고, 단 G가 NR19인 경우 R18은 저급알킬 또는 하이드록시알킬이다〕,(V는 0또는 1이고; R21은 NH, O, S 또는 SO2이다)또는 치환된 메틸렌 그룹인 화합물.
  3. 하기 일반식(Ⅱ)의 화합물 또는 약제학적으로 허용되는 염, 에스테르 또는 이의 예비약제.
    상기식에서, A는 R5C(O)-(CH2)W- (여기에서, W는 0내지 4이고 R5는 하이드록시, 알콕시, 티오알콕시, 아미노 또는 치환된 아미노이다); 알킬설포닐, (아릴)설포닐 또는 (헤테로사이클릭)설포닐; 아릴, 아릴알킬, 헤테로사이클릭 또는 (헤케로사이클릭)알킬; 또는 R90- 또는 R90NHC(O)- (여기에서, R90은 카복시, 알콕시카보닐, 알킬설포닐, 아릴, 아릴설포닐, 헤테로사이클릭 또는 (헤테로사이클릭)설포닐 중에서 선택된 치환체로 치환된 C1내지 C4의 직쇄 또는 측쇄이다)이고, R1은 수소; 저급알킬; 저급알케닐; 사이클로알킬알킬; 사이클로알케닐알킬; 아릴옥시알킬; 티오아릴옥시알킬; 아릴알콕시알킬; 아릴티오알콕시알킬; 또는 알콕시, 티오알콕시아릴 및 헤테로사이클릭중에서 선택된 치환체로 치환된 C1내지 C3의 직쇄 또는 측쇄이고, X는 CH2, CHOH, C(O), NH, O, S, S(O), SO2, N(O)또는 -P(O)O- 이고, R3는 저급알킬, 할로알킬, 저급알케닐, 사이클로알킬알킬, 사이클로알케닐알킬, 알콕시알킬, 티오알콕시알킬, (알콕시알콕시)알킬, 하이드록시알킬, -(CH2)eeNHR12(여기에서, ee는 1내지 3이고, R12는 수소, 저급알킬 또는 N-보호 그룹이다), 아릴알킬 또는 (헤테로사이클릭)알킬이고, R4는 저급알킬, 사이클로알킬알킬, 사이클로알케닐알킬 또는 아릴알킬이고, D는(여기에서, R73은 저급알킬이다),〔여기에서, M은 산소, 황 또는 NH이고; 저급알킬이다), 〔여기에서, M은 산소, 황 또는 NH이고; Q는 산소 또는 황이고; E는 산소, Q는 산소 또는 황이고; E는 산소, 황, CHR73(R73은 저급알킬이다), C=CH2또는 NR18(R18은 수소, 저급알킬, 하이드록시알킬, 알콕시, 아미노 또는 알킬아미노이다)이고; G는 없거나 CH2또는 NR19(R19는 수소 또는 저급알킬이다)이고, 단 G가 NR19인 경우 R18은 저급알킬 또는 하이드록시알킬이다〕,(V는 0또는 1이고; R21은 NH, O, S 또는 SO2이다)또는 치환된 메틸렌 그룹이다.
  4. 제 3항에 있어서, D는 (a) -CH(OH)CH2CH(CH3)2, (b)〔여기에서, M은 O,S 또는 NH이고; Q는 O 또는 S이고; E는 0, S, C=CH2, CHR73(R73은 저급알킬이다) 또는 NR18(R18은 수소, 저급알킬, 하이드록시알킬, 하이드록시, 알콕시, 아미노 또는 알킬아미노이다)이고; G는 없거나, CH2또는 NR19(R19는 수소 또는 저급알킬이다)이고, 단 G가 NR19인 경우 R18은 저급알킬 또는 하이드록시알킬이다〕, 또는 (c)-CH2CH(R22)C(O)NHR23(R22은 저급알킬이고, R23은 (헤테로사이클릭)알킬이다)이고, A는 R5C(O)- 이고, R5는 I)〔aa는 1내지 5이고, R6및 R7은 독립적으로, 수소, 하이드록시, 알콕시, 티오알콕시, 알콕시알콕시, 카복시, 알콕시카보닐, 할로겐, 아미노, 알킬아미노, 디알킬아미노, 알킬설포닐아미노, 아릴설포닐아미노, 알킬아미노카보닐아미노, 알킬아미노카보닐옥시, 알콕시카보닐옥시,(여기에서, dd는 1내지 5이다)및 R8-Z- (여기에서, Z는 O, S 또는 NH이고, R8는 하이드록시, 알콕시, 티오알콕시, 알콕시알콕시, 아미노, 알킬아미노,디알킬아미노, 카복시, 알콕시카보닐, 페닐, 및 치환된 페닐중에서 선택된 치환체로 치환된 C1내지 C6직쇄 또는 측쇄이다)이다〕, Ⅱ)(여기에서, R9는 O, S, SO2또는 C=O이다); 또는 Ⅲ)〔여기에서, R18은 수소, 저급알킬, N-보호 그룹 또는 R11-C(O)-(R11은 아미노알킬, (N -보호된)아미노알킬, 1-아미노-2-페닐에틸 또는 1-(N-보호된)아미노-2-페닐에틸이다)이다)〕중에서 선택되는 화합물.
  5. 3-(1-이미다졸릴)프로필 5(S)-아미노-6-사이클로헥실-4(S)-하이드록시-2(S)-이소프로필헥산 아미드의 2(S)-(1(S)-(4-(메톡시메톡시)피페리딘-1-일)카보닐)-22-페닐에톡시헥사노산 아미드; 3-(디메틸아미노)프로필 5(S)-아미노-6- 사이클로헥실-4(S)-하이드록시-2(S)-이소프로필 헥산아미드의 2(S)-(1(S)-(4(메톡시메톡시)피페리딘-1-일)카보닐)-2-페닐에톡시 헥사노산아미드; 3-(4-모르폴리닐)프로필 5(S)-아미노-6-사이클로헥산-4(S)-하이드록시-2(S)- 이소프로필헥산아미드의 2(S)-(1(S)-(4-(메톡시메톡시)피페리딘-1-일)카보닐)-페닐에톡시헥사노산 아미드; 3-(1-이미다졸릴)프로필 5(S)-아미노-6-사이클로헥실-4(S)-하이드록시-2(S)-이소프로필헥산 아미드의 N-(1(S)-(4-메톡시메톡시)피페리딘-1-일)카보닐)-2-페닐에틸-L-노르루식 아미드; 및 3-(4-모르폴리닐)프로필) 5(S)-아미노-6-사이클로헥실-4(S)-하이드록시-2(S)-이소프로필헥산아미드의 N-(1(S)-(4-(메톡시메톡시)프페리딘-1-일)카보닐)-2-페닐에틸-L-노르루실 아미드; 또는 약제학적으로 허용되는 염, 에스테르 또는 이의 예비약제중에서 선택되는 화합물.
  6. 3-(4-모르폴리닐)프로필 5(S)-아미노-6-사이클로헥실-4(S)-하이드록시-2(S)-이소프로필헥산 아미드의 2(S)-(1(S)-(4-(메톡시메톡시)피페리딘-1-일)카보닐)-2-페닐에톡시헥사노산 아미드; 또는 이의 약제학적으로 허용되는 염, 에스테르 또는 예비약제.
  7. 약제학적 담체 및 치료적 유효량의 제1항의 화합물을 함유하는, 레닌 억제용 약제학적 조성물.
  8. 치료적 유효량의 제1항의 화합물을 치료를 요하는 숙주에게 투여함을 특징으로 하여, 레닌을 억제하는 방법.
  9. 약제학 담체 및 치료적 유효량의 제1항의 화합물을 함유하는, 고혈압 또는 충혈성 심장 질환 치료용 약제학적 조성물.
  10. 치료적 유효량의 제1항의 화합물을 치료를 요하는 숙주에게 투여함을 특징으로 하여 고혈압 또는 충혈성 심장 질환을 치료하는 방법.
  11. 일반식 (Ⅲ)의 화합물, 이의 산 할라이드 또는 활성 에스테르 유도체.
    상기식에서, A는 R5C(O)-(CH2)W- (여기에서, W는 0내지 4이고, R5는 하이드록시, 알콕시, 티오알콕시, 아미노 또는 치환된 아미노이다); 알킬설포닐, (아릴)설포닐 또는 (헤테로사이클릭)알킬; 아릴, 아릴알킬, 헤테로사이클릭 또는 (헤테로사이클릭)알킬; 또는 R90-또는 R90NHC(O)- (여기에서, R90은 카복시, 알콕시카보닐, 알킬설포닐, 아릴, 아릴설포닐, 헤테로사이클릭 또는 (헤테로사이클릭)설포닐 중에서 선택된 치환체로 치환된 C1내지 C4직쇄 또는 측쇄이다)이고, R1은 수소; 저급알킬; 저급알케닐; 사이클로알킬알킬; 사이클로알케닐알킬; 아릴옥시알킬; 티오아릴옥시알킬; 아릴알콕시알킬; 아릴티오알콕시알킬; 또는 알콕시, 티오알콕시아릴 및 헤테로사이클릭중에서 선택된 치환체로 치환된 C1내지 C3의 직쇄 또는 측쇄이고, X는 CH2, CHOH, C(O), NH, O, S, S(O), SO2, N(O)또는 -P(O)O- 이고, R3은 저급알킬, 할로알킬, 저급알케닐, 사이클로알킬알킬, 사이클로알케닐알킬, 알콕시알킬, 티오알콕시알킬, (알콕시알콕시)알킬, 하이드록시알킬, -(CH2)eeNHR12(여기에서, ee는 1내지 3이고, R12는 수소, 저급알킬 또는 N-보호그룹이다), 아릴알킬 또는 (헤테로 사이클릭)알킬이다.
  12. 일반식 (Ⅲ)의 화합물, 이의 산 할라이드 또는 화성 에스테르 유도체.
    상기식에서, A는 4-메톡시메톡시모르폴린-1-알카보닐이고, R1은 아릴알킬이고, X는 O, NH 또는 S이고, R3는 저급알킬, 사이클로알킬알킬, 아릴알킬 또는 헤테로사이클릭 알킬이다.
  13. 일반식 (Ⅲ)의 화합물, 이의 산 할라이드 또는 활성 에스테르 유도체.
    상기식에서, A는 4-메톡시메톡시모르폴린-1-알카보닐이고, R1은 벤질이고, X는 산소이고, R3는 n-부틸이다.
  14. 치료적 유효량의 제1항의 화합물을 치료를 요하는 환자에게 투여함을 특징으로 하여, 녹내장을 치료하거나 안내압을 감소 및/또는 조절하는 방법.
  15. 치료적 유효량의 제1항의 화합물을 치료를 요하는 환자에게 투여함을 특징으로 하여, 후방 바이러스성 프로테아제를 억제하는 방법.
  16. 치료적 유효량의 제1항의 화합물을 이를 필요로 하는 환자에게 투여함을 특징으로 하여, 후방 바이러스성 감염을 치료하는 방법.
  17. 치료적 유효량의 제1항의 화합물 및 다른 고혈압 치료제를 치료를 요하는 숙주에게 투여함을 특징으로 하여, 고혈압 또는 충혈성 심장 질환을 치료하는 방법.
  18. 약제학적 담체를 치료적 유효량의 제1항의 화합물 및 다른 고혈압 치료제를 함유하는, 고혈압 또는 충혈성 심장질환 치료용 약제학적 조성물.
  19. 하기 일반식(Ⅲ)의 카복실산, 이의 산 할라이드 또는 이의 활성 에스테르 유도체를 H-T의 아민과 커플링시킴을 특징으로 하여, 제1항의 화합물을 제조하는 방법.
    상기식에서, A, R1, X, R3, 및 T는 상기 정의된 바와 같다.
  20. 제19항에 있어서, H-T가인 방법.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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EP0244083A3 (en) * 1986-04-01 1989-11-15 Kissei Pharmaceutical Co. Ltd. Amino acid derivatives

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EP0437508A4 (en) 1991-11-06
EP0364804A1 (en) 1990-04-25
EP0437508A1 (en) 1991-07-24
IL91780A0 (en) 1990-06-10
AU4416389A (en) 1990-05-01
AU639212B2 (en) 1993-07-22
CA1337909C (en) 1996-01-09
IL91780A (en) 1995-08-31
DK59991D0 (da) 1991-04-04
DK59991A (da) 1991-04-04
NZ230894A (en) 1991-07-26
JPH04505608A (ja) 1992-10-01
WO1990003971A1 (en) 1990-04-19

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