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    • 7. 发明申请
    • MATRIX METALLOPROTEINASE INHIBITORS
    • 基质金属蛋白酶抑制剂
    • WO2005016868A3
    • 2005-05-19
    • PCT/EP2004009087
    • 2004-08-12
    • GLAXO GROUP LTDHOLMES IANWATSON STEPHEN PAUL
    • HOLMES IANWATSON STEPHEN PAUL
    • C07C233/51C07C235/34C07C235/78C07C255/57C07D209/08C07D333/24C07C235/00C07C255/00
    • C07C235/78C07C233/51C07C235/34C07C255/57C07C2601/14C07D209/08C07D333/24
    • Compounds of Formula (I), wherein R represents optionally substituted -C4-12 alkyl, -C2-10alkylcycloalkyl, -C2-6 alkyl heterocycloalkyl, -C2-6alkylaryl, optionally substituted 5- or 6- membered aryl or heteroaryl, except pyridinyl. Z represents a bond, CH2, O, S, SO, SO2, NR , OCR R , CR R O, or Z, R and Q together form an optionally substituted fused tricyclic group; Q represents an optionally substituted 5- or 6- membered aryl or heteroaryl ring; X represents COR ; R represents CONH2, CO2H, CO2R , SO2R or SO2NR R , except that R ; may not represent CO2R when X is CONH2 ; R represents OR , or NR R ; R and R each independently represents H, C1-6 alkyl or C1-4 alkylaryl; R represents H or C1-6 alkyl; R represents C1-6 alkyl; R and R each independently represents H or C1-6 alkyl or R and R together with the nitrogen atom to which they are attached form a 5- or 6- membered ring which may optionally include 1 or more further heteroatoms selected from O, S and N; and physiologically functional derivatives thereof with the exception of [3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid and 3-(acetylamino)-4-cyclohexylphenyl]-butanedioic acid diethyl ether; butanedioic acid [3-methoxy-4-(phenylmethoxy)phenyl]; butanedioic acid [4-(phenylmethoxy)phenyl]; with the proviso that when R represents C4-12 alkyl, Z is other than a bond, O or CH2; and physiologically functional derivatives thereof , processes for their preparation, pharmaceutical formulations containing them and their use as inhibitors of matrix metallproteinase enzymes (MMPs) are described.
    • 式(I)化合物,其中R 1表示任选取代的-C 4-12烷基,-C 2-10烷基环烷基,-C 2-6烷基杂环烷基,-C 2-6烷基芳基,任选取代的5-或6-元芳基或杂芳基, 除了吡啶基。 Z表示键,CH 2,O,S,SO,SO 2,NR 4,OCR 4 R 5,CR 4 R 5 O或Z,R 1和Q一起形成 任选取代的稠合三环基团; Q代表任选取代的5元或6元芳基或杂芳基环; X代表COR 3; R 2代表CONH 2,CO 2 H,CO 2 R 7,SO 2 R 7或SO 2 NR 8 R 9,除了R 2; 当X是CONH 2时可能不代表CO 2 R 7; R 3表示OR 6或NR 8 R 9; R 4和R 5各自独立地表示H,C 1-6烷基或C 1-4烷基芳基; R6代表H或C1-6烷基; R 7表示C 1-6烷基; R 8和R 9各自独立地表示H或C 1-6烷基或者R 8和R 9与它们所连接的氮原子一起形成5-或6-元环,其可任选地 包括1个或多个选自O,S和N的其他杂原子; 以及除[3-(乙酰氨基)-4-环己基苯基] - 丁二酸和3-(乙酰氨基)-4-环己基苯基] - 丁二酸二乙酯以外的其生理学功能衍生物; 丁二酸[3-甲氧基-4-(苯基甲氧基)苯基]; 丁二酸[4-(苯基甲氧基)苯基]; 条件是当R 1代表C 4-12烷基时,Z不是键,O或CH 2; 及其生理功能衍生物,其制备方法,含有它们的药物制剂以及它们作为基质金属蛋白酶(MMP)抑制剂的用途。