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    THE PREPARATION AND USE OF ORTHO-SULFONAMIDO BICYCLIC HETEROARYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE AND TACE INHIBITORS
    10.
    发明公开
    THE PREPARATION AND USE OF ORTHO-SULFONAMIDO BICYCLIC HETEROARYL HYDROXAMIC ACIDS AS MATRIX METALLOPROTEINASE AND TACE INHIBITORS 失效
    生产和基质金属蛋白酶与TACE抑制剂ORTHO磺酰胺基二环杂芳基异羟肟酸衍生物的使用

    公开(公告)号：EP1021413A1

    公开(公告)日：2000-07-26

    申请号：EP98915523.9

    申请日：1998-04-14

    申请人： American Cyanamid Company

    发明人： LEVIN, Jeremy, Ian ,  ZASK, Arie ,  GU, Yansong ,  ALBRIGHT, Jay, Donald ,  DU, Xuemei

    IPC分类号： C07D215/54 ,  A61K31/63 ,  A61K31/47 ,  A61K31/44 ,  C07D401/12 ,  C07D471/04 ,  C07D513/04 ,  C07D498/04 ,  C07D495/04 ,  C07F9/547 ,  A61K31/66

    CPC分类号： C07D401/12 ,  C07D215/54 ,  C07D409/14 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  C07D513/04

    摘要： This invention provides, low molecular weight, non-peptide inhibitors of matrix metalloproteinases and TNF-α converting enzyme (TACE, tumor necrosis factor-α converting enzyme) of formula (B) wherein (B) is (1), (2), or (3); P and Q are (4) or (5), provided that when P is (4), Q is (5), and vice versa; T, U, W, and X are each, independently, carbon or nitrogen, provided that when T or U is carbon, either may be optionally substituted with R1; Y is carbon, nitrogen, oxygen or sulfur, provided that at least one of T, U, W, X, and Y is not carbon, and further provided that no more than 2 of T, U, W, and X are nitrogen; (6) is a phenyl ring or is a heteroaryl ring of ring 5-6 atoms which may contain 0-2 heteroatoms selected from nitrogen, oxygen, and sulfur, in addition to any heteroatoms defined by W or X; wherein the phenyl or heteroaryl ring may be optionally mono-, di-, or tri- substituted with R1; Z is a phenyl, naphthyl, heteroaryl, or heteroaryl fused to phenyl, wherein the heteroaryl moiety contains of 5-6 ring atoms and 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur; wherein the phenyl, naphthyl, heteroaryl, or phenyl fused heteroaryl moieties may be optionally mono-, di-, or tri-substituted with R1; R1 is hydrogen, halogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cyclocalkyl of 3-6 carbon atoms, -(CH¿2?)nZ, -OR?2¿, -CN, -COR2, perfluoroalkyl of 1-4 carbon atoms, -CONR2R3, -S(O)¿x?R?2-OPO(OR2)OR3¿, -PO(OR2)R3, -OC(O)NR2R3, -COOR?2, -CONR2R3, -SO¿3H, -NR?2R3, -NR2COR3, -NR2COOR3, -SO¿2NR?2R3, -NR2CONR2R3, -NR2C(=NR3)NR2R3, -SO¿2NHCOR4, -CONHSO¿2R?4, -tetrazol-5-yl, -SO¿2?NHCN, -SO2NHCONR?2R3¿, or Z; V is a saturated or partially unsaturated heterocycloalkyl ring of 5-7 ring atoms having 1-3 heteroatoms selected from N, O, or S, which may be optionally mono-, or di-substituted with R?2; R2 and R3¿ are each, independently, hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R4 is alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, cycloalkyl of 3-6 carbon atoms; perfluoroalkyl of 1-4 carbon atoms, Z or V; R5 is hydrogen, alkyl of 1-8 carbon atoms, alkenyl of 2-6 carbon atoms, alkynyl of 2-6 carbon atoms, Z, or V; n = 1-6; x = 0-2 or a pharmaceutically acceptable salt thereof.