KR960007537A - 글리신아미드 유도체, 그 제조방법 및 그를 함유하는 의약품 - Google Patents

글리신아미드 유도체, 그 제조방법 및 그를 함유하는 의약품 Download PDF

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KR960007537A
KR960007537A KR1019950025817A KR19950025817A KR960007537A KR 960007537 A KR960007537 A KR 960007537A KR 1019950025817 A KR1019950025817 A KR 1019950025817A KR 19950025817 A KR19950025817 A KR 19950025817A KR 960007537 A KR960007537 A KR 960007537A
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alkyl
alkoxy
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compound
halogen
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브라 쟝-피에르
드 코엥테 폴
데페이루 피에르
프레헬 다니엘
굴리 다니엘르
마프랑 쟝-피에르
비눙 에릭
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로날드 샤피라
사노피 (소시에떼 아노님)
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Abstract

본 발명은 글리신아미드 유도체, 구체적으로 콜레시스토키닌 수용체의 작용제인 하기 일반식의 화합물 및 그를 함유하는 약제학적 조성물에 관한 것이다.

Description

글리신아미드 유도체, 그 제조방법 및 그를 함유하는 의약품
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (12)

  1. 하기 일반식(I)의 화합물 및 그의 염.
    (I)
    [상기 식에서, -RI은 (C3-C8)알킬; Alk는 1 내지 4개의 탄소원자를 갖는 알킬렌이며, Ar1은 페닐기 또는 할로겐으로 선택적으로 치환되는 헤테로사이클, (C1-C3)알킬, (C1-C3)알콕시, 트리플루오로메틸 또는 히드록실인 아릴알킬-Alk-Ar1; 알킬은 (C1-C4)이고 시클로알킬은 (C3-C10)인 시클로알킬일킬; 히드록실, (C1-C3)알콕시 또는 상기 알킬을 동일한 탄소 원자에 두번 치환하는 것이 가능한 (C1-C3)알킬로 선택적으로 치환되는 (C3-C10)시클로알킬; 알콕시는 (C1-C4)이고 알킬은 (C2-C5)인 알콕시알킬; 또는 A는 (C1-C3)알킬, B는 (C1-C3)알킬 또는 페닐 또는 A와 B는 질소 원자가 결합되어 있고 피롤리돈, 피페리딘 및 모르폴린으로부터 선택된 헤테로사이클을 형성하며, r이 1,2 또는 3인 (AB)N-CO-(CH2)r-을 나타내고; -RⅡ는 수소; (C1-C6)알킬; (C1-C5)히드록시알킬; m은 1 내지 3의 정수이고, R2는 히드록실, (C1-C4)알콕시기, 벤질옥시기 또는 -NR3R4(상기 식에서, R3또는 R4은 독립적으로 수소, (C1-C4)알킬을 나타내거나 결합될 질소원자와 함께 피롤리딘, 피페리딘 및 모르폴린으로부터 선택된 헤테로사이클을 구성함)인 -(CH2)m-COR2; n 은 0 또는 1 내지 4의 정수를 나타내고, Ar2은 페닐 또는 할로겐, (C1-C3)알킬, (C1-C3)알콕시, 트리플루오로메틸, 히드록실 또는 벤질옥시로 선택적으로 치환된 헤테로사이클인 아르알킬기 -(CH2)n-Ar2; 알킬은 (C1-C4)이고 시클로알킬은 (C3-C10)인 시클로알킬알킬; (C1-C4)아미노알킬; x는 1 내지 4의 정수이고, R은 (C1-C4)알킬, 페닐, 벤질, 2-페닐에테닐 또는 벤질옥시이며, 방향족 고리가 할로겐, (C1-C3)알킬, (C1-C3)알콕시, 틀리플루오로메틸, 히드록실 또는 설포 또는 카르복실기로 선택적으로 치환되는 R-CO-NH-(CH2)x-; 구아니디노(C1-C4)알킬; 이미다졸릴(C1-C3)알킬; 알킬이 (C1-C3)인 알킬티오알킬; 아일 부분이 선택적으로 헤테로사이클이고 알킬부분이 (C1-C3)이며, 아릴은 할로겐, (C1-C3)알킬, (C1-C3)알콕시, 트루플루오로메틸 또는 히드록시로 선택적으로 치환된 아르알킬티오알킬; 알킬이 (C1-C3)이고 페닐은 할로겐, 히드록실, (C1-C3)알콕시, (C1-C3)알킬, 트리플루오로메틸, 니트릴 또는 니트로로 선택적으로 치환된 벤질옥시알킬; -RⅢ는 나프틸기; 퀴놀릴기; 이소퀴놀릴기; 탄소상에서 비치환되거나, (C1-C3)알킬 또는 (C1-C4)알킬카르보닐기, -(CH2)p-COR5(상기 식에서, p는 0 내지 4의 정수이며, R5는 R'5및 R"5와 함께 동일하거나 다를 수 있는 OR'5는 NR'5R"5을 나타내어 수소 또는 (C1-C4)알킬을 나타내며, 또는 달리 R'5및 R"5는 질소 원자와 함께 결합되어 (C1-C4)히드록시알킬, (C2-C6)알콕시알킬, (C2-C4)시아노일킬, 테트라히드로피라닐, 아다만틸아미노카르보닐(C1-C4)알킬 또는 q는 2 내지 4의 정수로서 탄소중의 하나는 인돌기의 페닐고리를 구성하여 고리를 구성하는 사슬 -(CH2)q-에 의하여 피페리딘을 형성함)에 의해 탄소 상에서 치환되거나 질소 상에서 치환되는 인돌릴기를 나타내며; -Ar은 2-메톡시-3-피리딜, 4-메톡시-5-피리미디닐 또는 (C-C)알킬, (C-C)알콕시, 할로겐 및 트리플루오로메틸로부터 선택된 적어도 두개의 다른 치환체를 함유하는 2-메톡시페닐기를 나타내고; 또는 Ar은 나프틸기를 나타내며; -또는 달리 RI및 RⅡ는 함께 하기의 기를 구성함.
    (상기 식에서, g는 0, 1 또는 2를 나타내고, Z는 (C1-C4)알킬, (C1-C3)알콕시 또는 할로겐을 나타냄)]
  2. 제1항에 있어서, 하기 일반식(Ia)의 화합물 및 그의 염.
    (Ia)
    [상기 식에서, RI및 RⅡ는 상기 일반식(I)에서 정의된 바와 같고, RIa은 (C5-C8)알킬; Alk는 1 내지 4개의 탄소원자를 함유하는 알킬렌이고 Ar1은 페닐기 또는 할로겐, (C1-C3)알킬, (C1-C3)알콕시, 트리플루오로메틸 또는 히드록시에 의하여 선택적으로 치환된 헤테로사이클을 나타내는 아릴알킬-Alk-Ar1;알킬이 (C1-C4)이고 시클로알킬은 (C3-C10)인 시클로알킬알킬; (C1-C3)알콕시, 히드록실 또는 (C1-C3)알킬로 선택적으로 치환되고, 상기 알킬은 두배의 동일한 탄소원자로 치환가능한 (C3-C10)인 알콕시알킬; 또는 A는 (C1-C3)알킬이고, B는 (C1-C3)알킬 또는 페닐이며 또는 기타의 A 및 B는 결합된 질소원자와 함께 피롤리딘, 피페리딘 및 모르폴린에서 선택된 헤테로사이클을 형성하며, r은 1,2 또는 3인 (AB)N-CO-(CH2)r-을 나타냄]
  3. 제1항에 있어서, Ar은 나프틸 기를 나타내고 RI은 제2항에 정의된 바와 같은 RIa및 그의 임의의 염인 것을 특징으로 하는 화합물 및 그의 염.
  4. 제1항에 있어서, RⅡ이 수소 이외의 것이고 치환체 RⅡ을 운반하는 탄소가 R형상인 것을 특징으로 하는 화합물 및 그의 염.
  5. 제1항에 있어서, RI및 RⅡ이 함께 하기의 링을 이루고 RⅡ을 운반하는 탄소가 S형상인 것을 특징으로 하는 화합물 및 그의 염.
    (상기 식에서, g 및 Z는 제1항에 정의된 바와 같음).
  6. 제1항에 따른 화합물을 제조하는 방법에 있어서, 하기 일반식의 아민:
    (Ⅱ)
    (상기 일반식에서, Ar 및 RI은 상기 정의된 바와 같음)을 하기 일반식(Ⅲ)의 N-가림된 아미노 산으로 처리하여,
    (Ⅲ)
    (상기 식에서 RⅡ은 상기 일반식 (I)에서 정의된 바와 같고 적합하기로는, RⅡ의 반응기는 가려짐)
    하기 일반식(Ⅳ)의 화합물은 제조하는 것을 특징으로 하는 방법.
    (Ⅳ)
    (상기 식에서, RI, Ar 및 RⅡ은 상기 정의된 바와 같고, 전환 후, 제1항에 따른 일반식(I)의 화합물 또는 그의 염 중 하나를 제조함).
  7. RI, Ar 및 RⅡ가 제1항에 정의된 바와 같은 것을 특징으로 하는 하기 일반식(Ⅳ)의 화합물.
    (Ⅳ)
  8. 활성제로서, 제1항 내지 제5항 중 어느 한 항에 따른 화합물을 함유하는 약제학적 조성물.
  9. 제8항에 있어서, 활성제가 적어도 하나의 약제학적 부형제와 혼합된 단위 투여 형태의 약제학적 조성물.
  10. 제9항에 있어서, 0.5 내지 1.000mg의 활성제를 함유하는 것을 특징으로 하는 약제학적 조성물.
  11. 하기 일반식(Ⅴ)의 화합물.
    (Ⅴ)
    (상기 식에서, RI, Ar 및 RⅡ가 제1항내 정의된 바와 같음)
  12. 하기 일반식의 화합물.
    (Ⅱ)
    (상기 식에서, Ar은 제1항내 정의된 바와 같고, R은 (C3-C10)시클로알킬을 나타내고, 임의로 히드록시, (C1-C3)알콕시 또는 (C1-C3)알킬에 의해 치환되며, 상기 알킬이 동일한 탄소 원자를 두번 치환시키는 것이 가능함)
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019950025817A 1994-08-19 1995-08-19 글리신아미드유도체,그제조방법및그를함유하는의약품 KR100190672B1 (ko)

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