KR910016765A - 아세트산 유도체 - Google Patents

아세트산 유도체 Download PDF

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KR910016765A
KR910016765A KR1019910003736A KR910003736A KR910016765A KR 910016765 A KR910016765 A KR 910016765A KR 1019910003736 A KR1019910003736 A KR 1019910003736A KR 910003736 A KR910003736 A KR 910003736A KR 910016765 A KR910016765 A KR 910016765A
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alanine
phenyl
group
amidinobenzoyl
alanyl
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알리히 레오
에덴호퍼 알브레흐트
뮐러 마르셀
트르제시악 아놀드
벨러 토마스
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쟝-자크 오게이, 롤란드 보러
에프. 호프만-라 롯슈 아크티엔게젤샤트
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Publication of KR910016765A publication Critical patent/KR910016765A/ko

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Abstract

내용 없음

Description

아세트산 유도체
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (15)

  1. 하기 일반식(Ⅰ)의 아세트산 유도체와 그의 수화물 또는 용매화물 및 그의 생리학적으로 이용가능한 염 :
    H2N(NH)C-X-Y-CO-Z-CH(Q1)COOQ2(Ⅰ)
    상기식에서, Q1은 수소, 메틸 또는 페닐이고, Q2는 수소, 페닐-저급 알킬 또는 생리학적 조건하에서 절단할 수 있는 저급 알킬이며, X는 1,4-페닐렌, 4번 위치의 C원자에 의해 그룹 Y에 결합된 1,4-피페리디닐렌, 또는 2,5-또는, 3,6-피리딜렌이고, Y는 일반식
    -(CH2)0-2-CONHCH(Q3)(CH2)1-3- (Y1)
    -CONHCH2CH(Q4)- (Y2)
    -(CH2)2NHCOCH2- (Y3)
    -NHCO(CH2)3- (Y4)
    또는
    (상기식에서, Q3)은 수소, 메틸, 페닐, -COOH, -COO-저급알킬, -CONH(CH2)2-COOH 또는 -CONH(CH2)2-COO-저급알킬이고, Q4는 수소, 메틸 또는 페닐이다)의 그룹이며, Z는 1,4-피페라지닐렌 그룹, 1번 위치의 N-원자에 의해 CO그룹에 결합된 1,4-피페리디닐렌 그룹 또는, 일반식 -NHCH(R1)- 또는 -NHCH(COR2)-[여기에서, R1은 수소, 메틸, 페닐 또는 -COO-저급 알킬이고, R2는 아미노 그룹에 의해 결합된 α-아미노 카복실산 또는 그의 에스테르 또는 아미드의 라디칼, 또는 일반식 -NHCH2CH2-Ar(이때, Ar은 페닐 또는, 저급 알킬, 저급 알콕시, -COOH, -COO-저급알킬, -O(CH2)1-4-COOH, -O(CH2)1--COO저급 알킬, -CONH2, -CONH-저급 알킬, -CON(저급 알킬)2피롤리디노일 또는 피페리디노일에 의해 치환된 페닐이다)의 그룹이거나, 또는 -CO-R2는 임의로 모노- 또는 디-저급-알킬화된 카바모일 그룹 또는, 피롤리디노일 또는 피페리디노일 그룹이다]의 그룹이다.
  2. 제1항에 있어서, 하기 일반식(Ⅰ-A)의 화합물과 그의 수화물 또는 용매화물 및 그의 생리학적으로 이용가능한 염 :
    H2N(HN)C-X-Yα-CONHCH(R11)CH2COOQ21(Ⅰ-A)
    상기식에서, X는 1,4-페닐렌 또는 4번 위치의 C원자에 의해 그룹 Yα에 결합된 1,4-피페리디닐렌이고, Yα는 일반식
    -(CH2)0-1-CONHCH(Qα)(CH2)1-2- (Y11)
    -(CH2)2NHCOCH2- (Y3)
    -NHCO(CH2)3- (Y4) 또는
    (상기식에서, Qα는 수소 또는 페닐이다)의 그룹이며, R11은 수소 또는 -CO-R22(여기에서, R22는 아미노 그룹에 의해 결합된 α-아미노카복실산 또는 그의 에스테르 또는 아미드의 라디칼이다)이고, Q21은 수소 또는 생리학적 조건하에서 절단할 수 있는 저급 알킬이다.
  3. 제1항에 있어서, X, Z, Q1및 Q2가 제1항에 나타낸 의미를 가지며, Y가 일반식 Y1, 특히 구조식
    -CONH(CH2)2-4, -CH2CONH(CH2)2-, -CONHCH(C6H5)CH2, -CONHCH(CONHCH2CH2COOH)CH2-, -CONHCH(COOH)CH2- 또는 -CONHCH(CH|3)CH2- 중의 하나의 그룹인 화합물.
  4. 제1항에 있어서, X, Y, Q1및 Q2가 제1항에 나타낸 의미를 가지며, Z가 구조식 -NHCH2-, -NHCH(CH3)-, -NHCH(C6H5)-, -NHCH(COO-이소부틸)-, -NHCH(CO-Val)-, -NHCH(CO-Phe)-, NHCH(CO-Phe)-, NNCH(CO-Tyr)-, -NHCH(CO-Ser-OC2H5), -NHCH(CO-Leu-O-이소프로필)- -NHCH(CONHCH2-CH2-C6H4-OCH3)-, -NHCH(CONHCH2CH2-C6H4-COOH)-, -NHCH(CONHCH2CH2-C6H4-OCH2COOH)-, -NHCH(CONH2)- 또는 -NHCH(피롤리디노일)-의 그룹인 화합물.
  5. 제2항에 있어서, 하기 화합물들을 포함하는 그룹으로부터 선택된 화합물 :
    N-[N-[4-(P-아미디노벤즈아미도)부티릴]-L-α-아스파틸-L-발린, N-[N-(P-아미디노벤조일)-β-알라닐]-β-알라닌 및 특히 N-[N-[N-(P-아미노벤조일)-β-알라닐]-L-α-아스파틸]-3-페닐-L-알라닌.
  6. 제2항에 있어서, 하기 화합물을 포함하는 그룹으로부터 선택된 화합물 :
    N-[N-[N-(1-아미디노-4-피페리디닐카보닐)-β-알라닐]-L-α-아스파틸]-3-페닐-L-알라닌, N-[N-[N-(P-아미디노페닐아세틸)-β-알라닐]-L-α-아스파틸-3-페닐-L-알라닌, N-[N-(P-아미디노페닐카바모일)부티릴]-L-α-아스파틸-3-페닐-L-알라닌, N-[N-[4-(P-아미디노페닐카바모일)아세틸]-L-α-아스파틸-3-페닐-L-알라닌, rac-N-[1-(P-아미디노벤조일)-3-피페리디닐카보닐)-β-알라닌, N-[4-(P-아미디노벤즈아미도)부티릴]-β-알라닌 및 N-[(DL)-N-(P-아미노벤조일)-3-페닐-β-알라닐]-β-알라닌.
  7. 제1항에 있어서, 하기 화합물을 포함하는 그룹으로부터 선택된 화합물 :
    N-[N-[N-(P-아미디노벤조일)-β-알라닐]-L-α-아스파틸]-L-류신 이소프로필 에스테르, N-[N-[N-(P-아미디노벤조일)-β-알라닐]-L-α-아스파틸]-L-발린, N-[N-[N-(P-아미디노벤조일)-β-알라닐]-L-α-아스파틸]-3-(P-하이드록실페닐)-L-알라닌, N-[N-[5-(P-아미디노벤즈아미도)발레릴-L-α-아스파틸]-3-페닐-L-알라닌, 이소부틸 N-[5-(P-아미디노벤즈아미도)발레릴-L-α-아스파테이트, N-[N-[N-(P-아미디노벤조일)-β-알라닐]-L-α-아스파틸]-L-세린 에틸 에스테르 및 N-[N-[[(R)-1-(P-아미디노벤조일)-3-피롤리디닐]-카보닐]-L-α-아스파틸]-3-페닐-알라닌.
  8. 제1항에 있어서, 하기 화합물을 포함하는 그룹으로부터 선택된 화합물 :
    N,N'-[[(S)-(P-아미디노벤즈아미도)에틸렌]디카보닐-β-알라닌, 2-N-(P-아미디노벤조일)-4-N-(2-카복실에틸)-L-아스파라진, N-[5-(P-아미디노벤즈아미도)발레릴]-β-알라닌, rac-N-[[1-[3-(1-아미디노-4-피페리디닐)프로피오닐]-3-피페리디닐]카보닐]-β-알라닌, N-[[(S)-1-(P-아미디노벤조일)-2-피롤리디닐]아세틸]-β-알라닌, (S)-3-[[N-(P-아미디노벤조일)-β-알라닐)아미노-3-[(P-메톡시펜에틸)카바모일]프로피온 산, N-[[(R-1-(P-아미디노벤조일)-3-피롤리디닐]-카보닐]-β-알라닌, N-[N-(P-아미디노벤조일)-2-메틸-β-알라닐]-L-α-아스파트 아미드, N-[N-(P-아미디노페닐)아세틸]-β-알라닐]-β-알라닌, rac-N-[[[1-(P-아미디노페닐)아세틸]-3-피페리디닐]카보닐]-β-알라닌 벤질 에스테르, rac-N-[[1-[P-(1-아미디노페닐)아세틸]-3-피페리디닐]카보닐]-β-알라닌, N-[N-[N-[3-(1-아미디노-)4-피페리디닐)프로피오닐]-β-알라닌-L-α-아스파틸]-3-페닐-L-알라닌, (S)-β-[[DL-N-(P-미디노벤조일)-3-메틸-β-알라닐]아미노]-(-옥소-1-피롤리딘부티르산, DL-N-[N-(P-아미디노벤조일)-β-알라닐]-3-메틸-β-알라닌, N-[DL-N-(P-아미디노벤조일)-β-알라닐]-DL-N-[-N-(P-아미노벤조일)-β-알라닌]-γ-β-알라닌, DL-N-[-N-(P-아미디노벤조일)-β-알라닐]-2-페닐β-알라닌, P-[2-[[N-[N-(P-아미디노벤조일)-β-알라닌]-L-α-아스파틸]-아미노]에틸]벤조산, DL-N-[N-(P-아미디노벤조일)-β-알라닐]-3-페닐-β-알라닌, [P-[2-[[N-[N-(P-아미디노벤조일)-β-알라닌]-L-α-아스파틸]-아미노]에틸]페녹시]아세트산, 1-[N-(P-아미디노벤조일)-β-알라닌]-4-피페리딘아세트산, 4-[N-(P-아미디노벤조일)-β-알라닐]-1-피페라진아세트산 및 N-[N-[N-[(5-아미-2-피리딜)카보닐]-β-알라닐]-L-α-아스파틸]-3-페닐-L-알라닌.
  9. 적어도 하나의 쉽게 절단할 수 있는 에스테르 그룹 또는 보호된 아미디노 그룹을 함유하는 하기 일반식(Ⅱ')의 아세트산 유도체 :
    X'-Y-CO-Z'-CH(Q1)-COO-Q2(Ⅱ')
    상기식에서, X'는 4번 위치가 임의로 보호된 아미디노 그룹에 의해 치환된 페닐 또는 4-피페리디닐이고, Y, Z, Q1및 Q2는 제1항에서와 동일한 의미를 갖는다.
  10. 약학적 활성 화합물로 사용하기 위한 제1항 내지 제8항중 어느 한 항의 화합물의 용도.
  11. a) 하기 일반식(Ⅱ)의 화합물로부터 적어도 하나의 보호 그룹을 제거하거나 또는 b) 하기 일반식(Ⅲ)의 니트릴중의 니트릴 그룹을 아미디노 그룹으로 전환시키고, 원한다면, 일반식(Ⅰ)의 화합물을 생리학적으로 허용가능한 염으로 전환시키거나 또는 일반식(Ⅰ)화합물의 염의 유리산 또는 염기로 전환시킴을 특징으로 하는 제1항에 따른 화합물의 제조방법 :
    X'-Y-CO-Z'-CH(Q1)-COO-Q5(Ⅱ)
    상기식에서, Q1및 Y는 제1항에 나타낸 의미를 갖고, X'는 4번 위치가 임의로 보호된 아미디노 그룹에 의해 치환된 페닐 또는 4-피페리디닐이며, Z' 및 Q5는 제1항의 Z 및 Q2와 동일한 의미를 갖는다.
  12. 혈소판에 대한 결합 단백질의 결합 및 또한, 혈소판 응집 및 세포-세포 결합에 의해 야기되는 질병의 치료 또는 예방을 위한, 활성 화합물로서 제1항 또는 제2항에 따른 화합물을 함유하는 약학제제.
  13. 혈소판에 대한 결합 단백질의 결합, 및 또한 혈소판 응집 및 세포-세포결합에 의해 야기되는 질병의 치료 또는 예방을 위한, 특히 혈소판 혈전, 혈전증, 대뇌 경색증, 심근 경색증, 염증 또는 동맥 경화증의 치료 또는 예방을 위한, 또는 종양치료제로서 또는 상처 치유제로서의 약제를 제조하기 위한 제1항 또는 제2항에 따른 화합물의 용도.
  14. 제11항의 방법 또는 그와 명백하게 화학적으로 동일한 방법에 의해 제조된 제1항 내지 제8항중 어느 한 항의 화합물.
  15. 상술한 바와 같은, 특히 실시예와 관련된 화합물, 제제, 방법 및 용도.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
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PT96983B (pt) 1998-07-31
TW219928B (ko) 1994-02-01
HUT56582A (en) 1991-09-30
JP2501252B2 (ja) 1996-05-29
EP0445796A3 (en) 1991-10-30
ZA911534B (en) 1991-11-27
EP0445796A2 (de) 1991-09-11
NO910934D0 (no) 1991-03-08
CA2037153A1 (en) 1991-09-10
ES2118067T3 (es) 1998-09-16
MX24811A (es) 1993-11-01
FI911148A0 (fi) 1991-03-07
IL97401A0 (en) 1992-06-21
MC2221A1 (fr) 1993-02-02
ATE167482T1 (de) 1998-07-15
MY105375A (en) 1994-09-30
FI911148A (fi) 1991-09-10
RU2072359C1 (ru) 1997-01-27
BR9100941A (pt) 1991-11-05
NO910934L (no) 1991-09-10
IL97401A (en) 1995-03-15
PH30963A (en) 1997-12-23
UY23197A1 (es) 1991-09-04
DE59109010D1 (de) 1998-07-23
EP0445796B1 (de) 1998-06-17
IE910778A1 (en) 1991-09-11
HRP930353A2 (en) 1996-06-30
HU910186D0 (en) 1991-08-28
IS3681A7 (is) 1991-09-10
NO301167B1 (no) 1997-09-22
PT96983A (pt) 1991-10-31

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