KR950704271A - 비시클릭 피브리노겐 길항제(Bicyclic Fibrinogen Antagonists) - Google Patents

비시클릭 피브리노겐 길항제(Bicyclic Fibrinogen Antagonists)

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KR950704271A
KR950704271A KR1019950702553A KR19950702553A KR950704271A KR 950704271 A KR950704271 A KR 950704271A KR 1019950702553 A KR1019950702553 A KR 1019950702553A KR 19950702553 A KR19950702553 A KR 19950702553A KR 950704271 A KR950704271 A KR 950704271A
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oxo
tetrahydro
acetic acid
phenylethyl
carbonyl
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윌리암 에드워드 본디넬
제임스 프랜시스 칼라한
윌리암 프랜시스 허프만
리차드 맥컬로크 키이난
토마스 웬-푸 쿠
케네쓰 알렌 뉴랜더
제임스 마틴 사마넨
아이린 니졸 우진스카스
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스튜어트 알. 수터
스미스클라인 비참 코포레이션
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Abstract

본 발명은 형소판 응집의 억제에 효과적인 하기 일반식(I), (II), (III)의 화합물 및 그의 제약상 허용되는 염과, 혈소판 응집 억제 작용을 나타내는 제약 조성물 및 혈소판 응집 억제 방법에 관한 것이다.
상기 각 식에서, A′은 O, S, N―R′ 또는 CHR′이고 A4는 N―R4또는 CHR4이며, R2는 산기 또는 에스테르기를 함유하는 측쇄이고, R1, R4및 R5는 H, 알킬 및 아릴알킬 등의 치환기이며, R6은 질소를 함유하는 측쇄이다.

Description

비시클릭 피브리노겐 길항제(Bicyclic Fibrinogen Antagonists)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (14)

  1. 하기 일반식(I)의 화합물 또는 그의 제약학적으로 허용되는 염.
    식 중, A1은 O, S, N―R1또는 CHR1이고; A4는 N―R4또는 CHR4이고, R2는 R7또는 R7에 의해 치환된 Q―C1―4―알킬, Q―C2―4―알케닐 또는 Q―C2―4―알키닐이고; R1, R4및 R5는 H, 또는 R11에 대해 정의된 기중의 1종 이상에 의해 임의 치환된 Q―C1―6―알킬, Q―C1―6―옥소알킬, Q―C2―6―알케닐, Q―C3―4―옥소알케닐, Q―C3―4―옥소알키닐, Q―C2―4―알키닐, Q―C3―6―시클로알키닐, Ar 또는 Het이고; Q는 H, C3―6―시클로알킬, Het 또는 Ar이고; R6은 W―(CR′2)q―Z―(CR′R10)r―U―(CR′2)s―V―이고; R7은 ―COR8, ―CORCR′2R9, ―C(S)R8, ―S(O)mOR′, ―S(O)mNR′R″, ―PO(OR′), ―PO(OR′)2, ―B(OR′)2, ―NO2및 Tet이고; R8은 ―OR′, ―NR′R″, ―NR′SO2R′, ―NR′OR′, ―OCR′2C(O)OR′, ―OCR′2OC(O)―R′, ―OCR′2C(O)NR′2, CF3또는 AA이고; R9는 ―OR′, ―CN, ―S(O)rR′,S(O)mNR′2, ―C(O)R′C(O)NR′2또는 ―CO2R′이고; R10은 H, C1―4―알킬 또는 ―NR′R″이고; R11은 H,할로, ―OR12, ―CN, ―NR′R12, ―NO2, ―CF3, CF3S(O)r, ―CO2R′, ―CONR′2, Q―C0―6―알킬, Q―C1―6―옥소알킬, Q―C2―6―알케닐, Q―C2―6―알키닐, Q―C0―6―알킬옥시, Q―C0―6―알킬아미노 또는 Q―C0―6―알킬―S(O)r이고; R12는 R′, ―C(O)R′, ―C(O)NR′2, ―C(O)OR15, ―S(O)mR′또는 S(O)mNR′2이고; R15는 H, C1―6―알킬 또는 Ar―C0―4―알킬이고; R′는 H, C1―6―알킬, C3―7―시클로알킬―C0―4―알킬 또는 Ar―C0―4―알킬이고; R″또는 R′, ―C(O)R′ 또는 ―C(O)OR15이고; R″′는 R″또는 AA2이고; AA1은 카르복실기가 임의로 보호되고 아미노기를 통해 결합되는 아미노산이고, AA2는 아미노기가 임의로 보호되고 카르복실기를 통해 결합되는 아미노산이고; U 및 V는 부재하거나, 또는 CO, CR′2, C(〓CR′2), S(O)n, O, NR′, CR′OR′, CR′(OR″)CR′2, CR′2CR′(OR″), C(O)CR′2, CR′2C(O), CONR′, NR′CO, OC(O), C(O)O, C(S)O, OC(S), C(S)NR′, NR′C(S), S(O)nNR′NR′S(O)n,N〓N, NR′NR′, NR′CR′2, CR′2NR′, CR′2O, OCR′2, C≡C 또는 CR′〓CR′이되, 단 U 및 V는 동시에 부재하지는 않고; W는 R′R″′N― 또는이고; Z는 (CH2)t또는 Het이고; m은 1 또는 2이고; n은 0 내지 3이고; q는 0 내지 3이고; r은 0 내지 2이고; s는 0 내지 2이고; t는 0 내지 2이다.
  2. 제1항에 있어서 R1및R4는 H, C1―6―알킬, Ar―C1―4―알킬 또는 C3―6―시클로알킬―C1―4―알킬이고, R2는 CH2CO2R′이고, R5는 H이고, (CR′R10)r―U―(CR′2)s―V는 (CH2)0-2NR′CO, (CH2)0―2ACONR′, (CH2)0―2CO, (CH2)2―0CH〓CH, (CH2)0―2C≡C,(CH2)1―3O 또는 (CH2)1―5이고, W는이고, Z는 피페리디닐, 피페라지닐 또는 (CH2)t인 화합물.
  3. 하기 일반식(II)의 화합물 또는 그의 제약학적으로 허용되는 염.
    식 중, R1, R2, R4R5및 R11은 제1항에서 정의한 바와 같고; R6은 W―(CR′2)q―Z―(CR′R10)r―U―(CR′2)s―V―(여기서, U, V 및 R′은 제1항에서 정의한 바와 같음)이고, R10은 H, C1―4―알킬 또는 ―NR′R″이고; W는 R′2N, H2NC(〓NH), H2NC(〓NH)NH 또는이고; Z는 Ar, C3―7―시클로알킬, (CH2)t또는 Het이다.
  4. 제3항에 있어서, R1은 H, C1―4―알킬 또는 C(O)R′이고, R2는 CH2CO2H 또는 CH2CH2CO2H이고, R4는 H, C1―6―알킬, C3―6―시클로알킬―C0―4―알킬 또는 Ar―C0―4―알킬이고, Z는 페닐, 6원 Het 또는 (CH2)t인 화합물.
  5. 제1항 내지 4항 중 어느 하나의 항에 있어서 R6은
    이거나 또는 R″HN―(CH2)5―U이고, 여기서 E는 N 또는 CH이고, R20은 수소, 아미노, 모노― 또는 디―C1―4―알킬아미노, 히드록시 또는 C1―4―알킬이고, U는 NR′CO, CONR′, (CH2)CO, CH〓CH, C≡C, CH2O, OCH2및 (CH2)2인 화합물.
  6. 하기 일반식(III)의 화합물.
    식 중, R2, R5, R11및 R″은 제1항에서 정의한 바와 같고
    이고, 여기서 E는 N 또는 CH이고, R20은 수소, 아미노, 모노― 또는 디―C1―4―알킬아미노, 히드록시 또는 C1―4―알킬이고, U는 NR′CO, CONR′, (CH2)CO, CH〓CH, C≡C이다.
  7. 제1항 내지 6항 중 어느 하나의 항에 있어서, R6은
    이고, 여기서 R′및 R″은 H 또는 C1―4―일킬이고, R20은 수소, 아미노, 모노― 또는 디―C1―4―알킬아미노, 히드록시 또는 C1―4―알킬이다.
  8. 다음 화합물,
    (R,S)―8―[[[4―(아미노이미노메틸)페닐]아미노]카르보닐]―2,3,4,5―테트라히드로―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―7―[[4―(아미노이미노메틸)벤조일]메틸아미노]―2,3,4,5―테트라히드로―1―메틸―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[2―(4―피리딜)에틸]아미노]카르보닐]―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[2―(2―피리딜)에틸]아미노]카르보닐]―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[5―(아미노펜틸)아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[4―(프로필)아미노메틸)페닐]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[[3―(아미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[3―[4―피페리디닐]프로필]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[4―(피리딜)에틸]아미노]카르보닐]―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[4―(3―피리딜)에틸]메틸아미노]카르보닐]―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―8―[[[2―(1H―이미다졸―1―일)에틸]아미노]카르보닐]―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―8―[[[3―(1H―이미다졸―1―일)프로필]아미노]카르보닐]―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[6―아미노헥실]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[6-아미노부틸]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2-페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―8―[[[2―(1H―이미다졸―4―일)에틸]아미노]카르보닐]―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―8―[[[2―(1―메틸―1H―이미다졸―5―일)에틸]아미노]카르보닐]―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―7―[[(4―아미노메틸)페닐]카르보닐]아미노]―2,3,4,5―테트라히드로―1―메틸―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[2―(4―피리딜)에틸]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[2―[4―[1―(메틸)피리디늄]에틸]메틸아미노]카르보닐]―4―[2―페닐에틸]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세테이트 요오다이드; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―[2―(시클로헥실)에틸]]―8―[[[2―(1―메틸―4―피페리디닐)에틸]메틸아미노]카르보닐]―1H―1,4―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[2―(1―메틸―4―피페리디닐)에틸]메틸아미노]카르보닐]――1H―1,4―벤조디아제핀―2―아세트산; [S―(R,S)]―8―[[[4―[N―(알라닐)아미노메틸]페닐]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―에틸―8―[[[4―(아미노이미노메틸)벤조일]아미노]―4,5―디히드로―2―메틸―3―옥소―4―(2―페닐에틸)―3H―1,4―벤조디아제핀; (R,S)―8―[[4―(아미노이미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―2―메틸―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[4―(아미노이미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트아미드; (R,S)―8―[[4―(아미노이미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트아미드; (R,S)―8―[[[4-(아미노이미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5-테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―에탄올; (R,S)―8―[2―[4―(아미노메틸)페닐]에틸]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; 7―[3―[(4―피리딜)프로필옥시]―2―(2―페닐에틸)―3―옥소―2,3,4,5―테트라히드로―1H―2―벤즈아제핀―4―아세트산; 7―[3―[(4―피페리디닐)프로필옥시]―2―(2―페닐에틸)―3―옥소―2,3,4,5―테트라히드로―1H―2―벤즈아제핀―4―아세트산; (R,S)―8―[[[3―(아미노메틸)페닐]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; 8―[1―[4―(4―피리딜)피페라지닐]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[4―(아미노메틸)―3―클로로―페닐]카르보닐]아미노]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; 2―[3―(4―피페리디닐)프로필옥시]―7―옥소―6,7,8,9―테트라히드로―5H―벤조시클로헵텐―6―아세트산; 3―[3―(4―피페리디닐)프로필옥시]―7―옥소―6,7,8,9―테트라히드로―5H―벤조시클로헵텐―6―아세트산; 또는(R,S)―8―[2―[4―2―(아미노피리딜)에틸]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산.
  9. 다음 화합물,(R,S)―8―[[[4―(아미노이미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―1―메틸―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[2―(1―피페라지닐)에틸]아미노]카르보닐]―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[2―(4―피페리디닐)에틸]아미노]카르보닐]――1H―1,4―벤조디아제핀―2―아세트산; (R,S)―7―[[(4―아미노아미노메틸)메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―2―(2―페닐에틸)―1H―2―벤조아제핀―4―아세트산; (R,S)―8―[[[(4―(아미노이미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―8―[[[4―(아미노이미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―4―메틸―3―옥소―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[2―(1―피페라지닐)에틸]메틸아미노]카르보닐]――1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[[2―(4―피페리디닐)에틸]메틸아미노]카르보닐]―1H―1,4―벤조디아제핀―2―아세트산; 또는 (R,S)―2,3,4,5―테트라히드로―3―옥소―4―[2―(시클로헥실)―에틸]―8―[[[2―(4―피페리디닐)에틸]메틸아미노]카르보닐]―1H―1.4―벤조디아제핀―2―아세트산.
  10. 다음 화합물, (R,S)―8―[[(4―아미노메틸)페닐]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―8―[[[2―[1―메틸―1,2,5,6―테트라히드로피리드―4―일]에틸]메틸아미노]카르보닐]―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[4―(피페리딘―4―일)―1(E)―부테닐]―1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―2―(시클로헥실에틸)―7―[[[2―(피페리딘―4―일)에틸]메틸아미노]카르보닐]――1H―2―벤조디아제핀―4―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―7―[[4―(피페리딘―4―일)피페라진―1―일]부틸]―1H―1,4―벤즈디제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―8―[[4―(피리드―4―일)카르보닐]――1H―1,4―벤조디아제핀―2―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―7―[[2―(피페리딘―4―일)에틸]메틸아미노]카르보닐]―1H―2―벤조아제핀―4―아세트산; (R,S)―2,3,4,5―테트라히드로―3―옥소―2―(2―페닐에틸)―7―[[[2―(피페리딘―4―일)에틸]메틸아미노]카르보닐]―1H―2―벤즈아제핀―4―아세트산; (R,S)―7―[[(2―(2―아미노)피리드―4―일]에틸]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―2―벤즈아제핀―4―아세트산; 7―[1―[4―(피페라진―1―일)부트―1―이닐]]―2―(2―페닐에틸)―3―옥소―2,3,4,5―테트라히드로―1H―2―벤즈아제핀―4―아세트산; (R,S)―7―[[(2―(피페리딘―4―일)에틸]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―2―메틸―3―옥소―2―(2―페닐에틸)―1H―2―벤즈아제핀―4―아세트산; (R,S)―7―[[[4―아미노메틸]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―2―(2―페닐에틸)―1H―2―벤즈아제핀―4―아세트산; (R,S)―8―[[[4―(N,N―디메틸아미노메틸)페닐]아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; 8―[[[2―(2―아미노―피리딘―4―일)에틸]메틸아미노]카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(2―페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산; 또는 (R,S)―7―[(4,4′―비피페리딘―1―일)카르보닐]―2,3,4,5―테트라히드로―3―옥소―4―(페닐에틸)―1H―1,4―벤조디아제핀―2―아세트산;
  11. 하기 식의 중간체 화합물.
    식 중, E는 N 또는 CH이고, R20은 수소, 아미노, 모노― 또는 디―C1―4―알킬아미노, 히드록시 또는 C1―4―알킬이고, Rp는 질소 보호기이고, L2는 CHO, CO2R′, C≡C―H, OH, C1, Br, I, CH2―T 또는 NR′R″이고, T는 CF3SO3, OH, HNR″, C1, Br 또는 I이다.
  12. 제1항 내지 10항 중 어느 하나의 항에 기재된 화합물 및 제약학적으로 허용되는 담체를 포함하는 제약 조성물.
  13. 약제 제조시 사용하기 위한 제1항 내지 10항 중 어느 하나의 항에 기재된 화합물.
  14. 혈소판 응고 방지를 필요로 하는 동물에게 제1항 내지 10항 중 어느 하나의 항에 기재된 화합물 유효량을 투여하는 것을 포함하느 혈소판 응고 방지 방법.
    ※ 참고사항:최초출원 내용에 의하여 공개하는 것임.
KR1019950702553A 1992-12-21 1993-12-21 비시클릭피브리노겐길항제 KR100318572B1 (ko)

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Families Citing this family (48)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5939412A (en) * 1992-06-26 1999-08-17 Smithkline Beecham Corporation Bicyclic fibrinogen antagonists
ES2190428T3 (es) * 1991-06-28 2003-08-01 Smithkline Beecham Corp Antagonistas biciclicos de fibrinogeno.
US5565449A (en) * 1991-10-18 1996-10-15 Genentech, Inc. Nonpeptidyl integrin inhibitors having specificity for the GPIIb IIIa receptor
MA23420A1 (fr) * 1994-01-07 1995-10-01 Smithkline Beecham Corp Antagonistes bicycliques de fibrinogene.
US6458784B1 (en) 1994-06-29 2002-10-01 Smithkline Beecham Corporation Vitronectin receptor antagonists
MX9700041A (es) * 1994-06-29 1997-04-30 Smithkline Beecham Corp Antagonistas de receptor de vitronectina.
JPH10504807A (ja) * 1994-06-29 1998-05-12 スミスクライン・ビーチャム・コーポレイション ビトロネクチン受容体拮抗剤
WO1996006087A1 (en) * 1994-08-22 1996-02-29 Smithkline Beecham Corporation Bicyclic compounds
EP0796252A4 (en) * 1994-12-09 1998-02-04 Smithkline Beecham Corp BICYCLIC FIBRINOGEN ANTAGONISTS
WO1996026190A1 (en) * 1995-02-22 1996-08-29 Smithkline Beecham Corporation Integrin receptor antagonists
US5719144A (en) * 1995-02-22 1998-02-17 Merck & Co., Inc. Fibrinogen receptor antagonists
DE19516483A1 (de) * 1995-05-05 1996-11-07 Merck Patent Gmbh Adhäsionsrezeptor-Antagonisten
US5977101A (en) * 1995-06-29 1999-11-02 Smithkline Beecham Corporation Benzimidazoles/Imidazoles Linked to a Fibrinogen Receptor Antagonist Template Having Vitronectin Receptor Antagonist Activity
US5852045A (en) * 1995-10-19 1998-12-22 Merck & Co., Inc. Fibrinogen receptor antagonists
KR19990076876A (ko) * 1995-12-29 1999-10-25 스티븐 베네티아너 비트로넥틴 수용체 길항제
EP0906103A1 (en) * 1995-12-29 1999-04-07 Smithkline Beecham Corporation Vitronectin receptor antagonists
US6011029A (en) 1996-02-26 2000-01-04 Bristol-Myers Squibb Company Inhibitors of farnesyl protein transferase
NZ334438A (en) 1996-09-03 2000-10-27 Smithkline Beecham Corp (S)-7-[(4,4'-bipiperidrin-1-yl)carbonyl]-2,3,4,5-tetrahydro-4-methyl-3-oxo-1H-1,4-benzodiazepine-2-acetic acid hydrochloride as a platelet aggregation inhibitor
UA60311C2 (uk) * 1996-10-02 2003-10-15 Смітклайн Бічам Корпорейшн Антагоністи рецептора вітронектину, спосіб одержання цих сполук та фармацевтична композиція
US20030125317A1 (en) 1996-10-02 2003-07-03 Smithkline Beecham Corporation Vitronectin receptor antagonists
DE19653647A1 (de) 1996-12-20 1998-06-25 Hoechst Ag Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung
US6482821B2 (en) 1996-12-20 2002-11-19 Hoechst Aktiengellschaft Vitronectin receptor antagonists, their preparation and their use
US6218387B1 (en) 1996-12-20 2001-04-17 Hoechst Aktiengesellschaft Vitronectin receptor anatagonists, their preparation and their use
DE19653645A1 (de) * 1996-12-20 1998-06-25 Hoechst Ag Vitronectin - Rezeptorantagonisten, deren Herstellung sowie deren Verwendung
WO1998029561A1 (en) * 1996-12-27 1998-07-09 Smithkline Beecham Plc Enzymatic resolution of benzodiazepine-acetic acid esters with a lipase
US6239138B1 (en) * 1997-07-25 2001-05-29 Smithkline Beecham Corporation Vitronectin receptor antagonist
AU8689798A (en) * 1997-08-04 1999-02-22 Smithkline Beecham Corporation Integrin receptor antagonists
HRP990246A2 (en) 1998-08-07 2000-06-30 Du Pont Pharm Co Succinoylamino benzodiazepines as inhibitors of a beta protein production
NZ525513A (en) 1998-08-07 2004-09-24 Pont Pharmaceuticals Du Succinoylamino lactams as inhibitors of Abeta protein production
US6339083B1 (en) 1998-12-14 2002-01-15 Bayer Aktiengesellschaft Multiheterocyclic pharmAceuticals
IL142816A0 (en) 1998-12-24 2002-03-10 Du Pont Pharm Co SUCCINOYLAMINO BENZODIAZEPINES AS INHIBITORS OF Aβ PROTEIN PRODUCTION
GB9908662D0 (en) * 1999-04-15 1999-06-09 Smithkline Beecham Plc Novel process for preparing benzodiazepines
CO5180550A1 (es) 1999-04-19 2002-07-30 Smithkline Beecham Corp Inhibidores de fab i
US6960576B2 (en) 1999-09-13 2005-11-01 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of Aβ protein production
US6503902B2 (en) 1999-09-13 2003-01-07 Bristol-Myers Squibb Pharma Company Hydroxyalkanoylaminolactams and related structures as inhibitors of a β protein production
EP1222176A1 (en) 1999-10-08 2002-07-17 Bristol-Myers Squibb Pharma Company AMINO LACTAM SULFONAMIDES AS INHIBITORS OF A$g(b) PROTEIN PRODUCTION
WO2001035964A1 (en) 1999-11-18 2001-05-25 Antexpharma, Inc. Substituted 1-benzazepines and derivatives thereof
US6525044B2 (en) 2000-02-17 2003-02-25 Bristol-Myers Squibb Company Succinoylamino carbocycles and heterocycles as inhibitors of a-β protein production
CN1436175A (zh) 2000-04-03 2003-08-13 布里斯托尔-迈尔斯斯奎布药品公司 作为Aβ－蛋白生产抑制剂的环状内酰胺
BR0110051A (pt) 2000-04-03 2004-12-07 Bristol Myers Squibb Pharma Co Composto, uso do composto, composição farmacêutica e método de tratamento do mal de alzheimer
EP1289966A1 (en) 2000-04-11 2003-03-12 Bristol-Myers Squibb Pharma Company SUBSTITUTED LACTAMS AS INHIBITORS OF A$g(b) PROTEIN PRODUCTION
EP1275643A4 (en) 2000-04-19 2009-06-03 Chugai Pharmaceutical Co Ltd DERIVATIVES OF VITAMIN D
WO2001092235A1 (en) 2000-06-01 2001-12-06 Bristol-Myers Squibb Pharma Company LACTAMS SUBSTITUTED BY CYCLIC SUCCINATES AS INHIBITORS OF Aβ PROTEIN PRODUCTION
CZ20032258A3 (cs) 2001-02-23 2004-01-14 Merck & Co., Inc. N-substituované nearylové heterocyklické sloučeniny
WO2002080928A1 (en) 2001-04-03 2002-10-17 Merck & Co., Inc. N-substituted nonaryl-heterocyclo amidyl nmda/nr2b antagonists
JP5258561B2 (ja) 2005-07-15 2013-08-07 アルバニー モレキュラー リサーチ， インコーポレイテッド アリール置換およびヘテロアリール置換テトラヒドロベンズアゼピンならびにノルエピネフリン、ドーパミンおよびセロトニンの再取り込みを遮断するためのその使用
GB0517292D0 (en) * 2005-08-24 2005-10-05 Univ Dundee Cell migration modulating compounds
CN115667236B (zh) * 2020-04-26 2024-04-26 江苏恩华药业股份有限公司 1,5-二氢-2,4-苯二氮䓬-3-酮衍生物及其应用

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL8005133A (nl) * 1980-09-12 1982-04-01 Duphar Int Res Fenylpiperazinederivaten met antiagressieve werking.
DE3701344A1 (de) * 1986-01-21 1987-07-23 Boehringer Ingelheim Kg Neue thieno-1,4-diazepine
DE3702755A1 (de) * 1987-01-30 1988-08-11 Hoechst Ag 3,5-di-tert.-butyl-4-hydroxybenzoesaeureamid, verschiedene von dessen derivaten, verfahren zur herstellung dieser verbindungen, die sie enthaltenden arzneimittel und ihre verwendung
JPH04211071A (ja) * 1990-03-05 1992-08-03 Hokuriku Seiyaku Co Ltd 多環式化合物
JPH06502643A (ja) * 1990-11-01 1994-03-24 スミスクライン・ビーチャム・コーポレイション フィブリノーゲン拮抗剤としてのγ−ターンペプチド模倣化合物
EP0495750A3 (en) * 1991-01-14 1992-09-16 Ciba-Geigy Ag Heterocyclic hydroxylamine
ES2190428T3 (es) * 1991-06-28 2003-08-01 Smithkline Beecham Corp Antagonistas biciclicos de fibrinogeno.
GB9200293D0 (en) * 1992-01-08 1992-02-26 Wyeth John & Brother Ltd Piperazine derivatives

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