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    QUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS
    1.
    发明公开
    QUINAZOLINE DERIVATIVES AS ANGIOGENESIS INHIBITORS 有权
    喹唑啉衍生物的血管生成抑制剂

    公开(公告)号：EP1154774A1

    公开(公告)日：2001-11-21

    申请号：EP00902730.1

    申请日：2000-02-08

    申请人： AstraZeneca AB ,  Zeneca-Pharma SA

    发明人： HENNEQUIN, Laurent, François, Andre ,  PLE, Patrick ,  STOKES, Elaine, Sophie, Elizabeth ,  MCKERRECHER, Darren

    IPC分类号： A61K31/505 ,  C07D401/14 ,  C07D413/14 ,  C07D417/12 ,  C07D405/12 ,  C07D401/12

    CPC分类号： A61K31/505 ,  A61K31/517 ,  C07D231/12 ,  C07D233/56 ,  C07D239/88 ,  C07D239/94 ,  C07D249/08 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04

    摘要： The invention relates to the use of compounds of formula (I), wherein ring C is an 8, 9, 10, 12 or 13-membered bicyclic or tricyclic moiety which optionally may contain 1-3 heteroatoms selected independently from O, N and S; Z is -O-, -NH-, -S-, -CH2- or a direct bond; n is 0-5; m is 0-3; R2 represents hydrogen, hydroxy, halogeno, cyano, nitro, trifluoromethyl, C¿1-3?alkyl, C1-3alkoxy, C1-3alkylsulphanyl, -NR?3R4¿ (wherein R?3 and R4¿, which may be the same or different, each represents hydrogen or C¿1-3?alkyl), or R?5X1¿- (wherein X?1 and R5¿ are as defined herein; R1 represents hydrogen, oxo, halogeno, hydroxy, C¿1-4?alkoxy, C1-4alkyl, C1-4alkoxymethyl, C1-4alkanoyl, C1-4haloalkyl, cyano, amino, C2-5alkenyl, C2-5alkynyl, C1-3alkanoyloxy, nitro, C1-4alkanoylamino, C1-4alkoxycarbonyl, C1-4alkylsulphanyl, C1-4alkylsulphinyl, C1-4alkylsulphonyl, carbamoyl, N-C1-4alkylcarbamoyl, N,N-di(C1-4alkyl)carbamoyl, aminosulphonyl, N-C1-4alkylaminosulphonyl, N,N-di(C1-4alkyl)aminosulphonyl, N-(C1-4alkylsulphonyl)amino, N-(C1-4alkylsulphonyl)-N-(C1-4alkyl)amino, N,N-di(C1-4alkylsulphonyl)amino, a C3-7alkylene chain joined to two ring C carbon atoms, C1-4alkanoylaminoC1-4alkyl, carboxy or a group R?56X10¿ (wherein X?10 and R56¿ are as defined herein); and salts thereof, in the manufacture of a medicament for use in the production of an antiangiogenic and/or vascular permeability reducing effect in warm-blooded animals, processes for the preparation of such compounds, pharmaceutical compositions containing a compound of formula (I) or a pharmaceutically acceptable salt thereof as active ingredient and compounds of formula (I). The compounds of formula (I) and the pharmaceutically acceptable salts thereof inhibit the effects of VEGF, a property of value in the treatment of a number of disease states including cancer and rheumatoid arthritis.