KR950032117A - 1H-인돌-3-글리옥실아미드 s_LA₂ 억제제 - Google Patents

1H-인돌-3-글리옥실아미드 s_LA₂ 억제제 Download PDF

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KR950032117A
KR950032117A KR1019950007267A KR19950007267A KR950032117A KR 950032117 A KR950032117 A KR 950032117A KR 1019950007267 A KR1019950007267 A KR 1019950007267A KR 19950007267 A KR19950007267 A KR 19950007267A KR 950032117 A KR950032117 A KR 950032117A
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dioxoethyl
amino
oxy
indol
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제임스 바흐 니콜라스
델란 딜라드 로버트
엘리자베쓰 드라헤임 수잔
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피터 지. 스트링거
일라이 릴리 앤드 캄파니
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/30—Indoles; Hydrogenated indoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to carbon atoms of the hetero ring
    • C07D209/42—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D209/22—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with an aralkyl radical attached to the ring nitrogen atom
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    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P37/00—Drugs for immunological or allergic disorders
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Abstract

신규한 1H-인돌 -3-글리옥실아미드류가, 패혈증성 쇼크와 같은 증상의 치료를 위해 지방산의SPLA2매개 방출을 억제하는 상기 인돌 화합물의 용도와 함께 개시되어 있다.

Description

1H-인돌 -3-글리옥실아미드SPLA2억제제
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (4)

  1. 하기 일반식(Ⅰ)의 1H-인돌 -3-글리옥실아미드;
    상기식에서, X는 각각 독립적으로 산소 또는 황이고; R1은 하기 (a), (b) 및 (c)로구성된 군중에서 선택되고; (a)는 C7-C20알킬, C7-C20알케닐, C7-C20알키닐, 카보사이클릭, 라디칼, 또는 헤테로사이클릭 라디칼이거나 또는 (b)는 하나 이상의 독립적으로 선택된 비간섭 치환기로 치환된 (a)의 구성원이거나 또는 (c)는 -(L)-R80의 그룹(이때 -(L)-은 탄소, 수소, 산소, 질소 및 황중에서 선택된 원자 1내지 12개로 구성된이가 연결 그룹이고, -(L)-에서, 원자들의 조합은 (ⅰ)탄소와 수소만으로 이루어 지거나, (ⅱ)황만으로 이루어 지거나, (ⅲ)산소만으로 이루어지거나, (iv)질소와 수소만으로 이루어지거나, (v)탄소, 수소 및 황으로만 이루어지거나, 및 (ⅵ)탄소, 수소 및 산소만으로 이루어진 그룹중에서 선택되고, R8o은 (a) 또는 (b)중에서 선택된 그룹이다)이고; R2는 수소, 할로, C1-C3알킬, C3-C4사이클로알킬, C3-C4사이클로알케닐, -O-(C1-C2알킬), -S-(C1-C|2알킬), 또는 수소가 아닌 총 1내지 3개의 원자를 갖는 비간섭 치환기이고, R4및 R5는 독립적으로 수소, 비간섭 치환기, 또는 -(La-(산성 그룹)의 그룹(이때 -(La)-는 1내치 4의 산 링커 길이를 갖는산 링커이다)중에서 선택되나, 단 R4및 R5중 적어도 하나는 -(La-(산성그룹)의 그룹이어야 하며; R6및 R7은 각각 독립적으로 수소, 비간섭 치환기, 카보사이클릭 라디칼, 비간섭 치환기로 치환된 카보사이클릭 라디칼, 헤테로사이클릭 라디칼 및 비간섭 치환기로 치환된 헤테로사이클릭 라디칼중에서 선택된다.
  2. 하기 일반식(Ⅲ)의 1H-인돌-3-글리옥실아미드 또는 그의 약학적으로 허용되는 염, 용매화물 또는 전구약물 유도체;
    상기식에서, R21은 -(L2)-R81그룹 [이때 -(L2)-는 구조식을 갖는 이가 연결 그룹이고, 이때, p는 1내지 5이고, R81은 하기 (a) 또는 (b)중에서 선택된 그룹이고, (a)는 하기 일반식으로 구성된 그룹중에서 선택되고,
    (상기식에서, R10은 할로, C1-C10알킬, C1-C10알콕시, -S-(C1-C10알킬), 및 C1-C10할로알킬중에서 독립적으로 선택된 라디칼이고, t는 0 내지 5의 수이다); 및 (b)는 C1-C6알킬, C1-C6알콕시, C1-C6할로알콕시, C1-C6할로알킬, 브로모, 클로로, 플루오로 또는 요오드로 구성된 그룹중에서 독립적으로 선택된 하나 이상의 비간섭 치환기로 치환된 (a)의 구성원이다〕이고; R24는 수소, C1-C6알킬, C1-C6알콕시, C2-C6할로알콕시, C2-C6할로알킬, 브로모, 클로로, 플루오로 또는 요오도 또는 -(La)-(산성그룹)-중에서 선택되고, 이때 R24에 대한 산 링커 -(La)-는 하기 구조식으로 부터 선택되고,
    (상기식에서 R은 알킬이다)
    산성 그룹은 -CO2H, -SO3H, -P(O)(OH)2로 부터 선택되고; R25는 수소, C1-C6알킬, C1-C6알콕시, C2-C6할로알콕시, C2-C6할로알킬, 브로모, 클로로, 플루오로 또는 요오도 또는 -(La)-(산성그룹)인 그룹〔이때 R25에서 산 -(La)-인 산 링커는 하기 일반식으로 이루어진 그룹중에서 선택되고;
    (상기식에서, R84및 R85는 각각 수소, C1-C10알킬, 아릴, C1-C10알크아릴, C1-C10아르알킬, 카복시, 카브알콕시 및 할로중에서 독립적으로 선택된다), 산성 그룹은 -CO2H, -SO3H, -P(O)(OH)2부터 선택된다〕 중에서 선택되나, R24또는 R25중 적어도 하나는 -(La)-(산성 그룹)인 그룹이어야 하고, R26및 R27은 각각 독립적으로 수소, 또는 C1-C6알킬, C1-C6알콕시, C2-C6할로알콕시, C2-C6할로알킬, 브로모, 클로로, 플루오로, 또는 요오도 중에서 각각 독립적으로 선택된다.
  3. 하기 (A)내지 (P)로 구성된 그룹중에서 선택된 1H-인돌-3-글리옥실아미드 또는 그의 약학적으로 허용되는 염, 용매화물, 또는 전구약물 유도체; (A)[[3-(2-아미노-1,2-디옥소에틸)-2-메틸-1-(페닐메틸)-1H-인돌-4-일〕옥시〕아세트산, (B)d1-2-〔〔3-(2-아미노-1,2-디옥소에틸)-2-메틸-1-(페닐메틸)-1H-인돌-4-일〕옥시〕프로판산, (C)〔〔3-(2-아미노-1,2-디옥소에틸)-1-(〔1,1′-비페닐〕-2-일메틸)-2-메틸-1H-인돌-4-일〕옥시〕아세트산,(D)〔〔3-(2-아미노-1,2-디옥소에틸)-1-(〔1,1′-비페닐〕-3-일메틸)-2-메틸一1H-인돌-4-일〕옥시〕아세트산, (E)〔〔3-2-아미노-1,2-디옥소에틸)-1-(〔1,1′-비페닐〕-4-일메틸)-2-메틸-1H-인돌-4-일〕옥시〕아세트산,(F)〔〔3-(2-아미노-1,2-디옥소에틸)-1-(〔2,6-디클로로페닐)메틸〕-2-메틸-1H-인돌-4-일〕옥시〕아세트산,(G)〔〔3-(2-아미노-1,2-디옥소에틸)-1-〔4-(플루오로페닐)메틸〕-2-메틸-1H-인돌-4-일〕옥시〕아세트산, (H)〔〔3-(2-아미노-1,2-디옥소에틸)-2-메틸-1-(〔1-나프탈레닐)메틸〕-1H-인돌-4-일〕옥시〕아세트산, (I)〔〔3-(2-아미노-1,2-디옥소에틸)-2-에틸-1-(페닐메틸)-1H-인돌-4-일〕옥시〕아세트산,(J)〔〔3-(2-아미노-1,2-디옥소에틸)-1-〔(3-클로로페닐)메틸〕-2-에틸-1H-인돌-4-일〕옥시〕아세트산, (K)〔〔3-(2-아미노-1,2-디옥소에틸)-1-(〔1,l′-비페닐)-2-일메틸)-2-에틸-1H-인돌-4-일〕옥시〕아세트산, (L)〔〔3-(2-아미노-1,2-디옥소에틸)-1-(〔〔1,1′-비페닐〕-2-일메틸)-2-프로필-1H-인돌-4-일〕옥시〕아세트산, (M)〔〔3-(2-아미노-1,2-디옥소에틸)-2-사이클로프로필-1-(페닐메틸)-1H-인돌-4-일〕옥시〕아세트산,(N)〔〔3-(2-아미노-1.2-디옥소에틸)-1-(〔〔1,1′-비페닐〕-2-일메틸)-2一사이클로프로필-1H-인돌-4-일〕옥시〕아세트산, (O)4-〔〔3-(2-아미노-l,2-디옥소에틸)-2-에틸-1-(페닐메틸)-1H-인돌-5-일〕옥시〕부탄산, 및 (P)(A) 내지 (O)의 혼합물.
  4. 제1항 또는 2항 또는 3항중 어느 한 항에서 청구한 1H-인돌-3-글리옥실아미드와그에 대한 약학적으로 허용되는 담체 또는 희석제를 함께 포함하는 약학 제형.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019950007267A 1994-04-01 1995-03-31 1H-인돌-3-글리옥실아미드sPLA2억제제 KR100368707B1 (ko)

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