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    Sulfonamide substituted aspartic acid interleukin-1'beta' converting enzyme inhibitors
    9.
    发明专利
    Sulfonamide substituted aspartic acid interleukin-1'beta' converting enzyme inhibitors 未知

    公开(公告)号：NZ334887A

    公开(公告)日：2000-09-29

    申请号：NZ33488797

    申请日：1997-10-09

    Applicant: BASF AG ,  WARNER LAMBERT CO

    Inventor： ALLEN HAMISH JOHN ,  BRADY KENNETH DALE ,  HARTER WILLIAM GLEN ,  LUNNEY ELIZABETH ANN ,  PLUMMER MARK STEPHEN ,  SAWYER TOMI ,  SHAHRIPOUR AURASH ,  WALKER NIGEL

    IPC: A61K31/192 ,  A61K31/341 ,  A61P1/00 ,  A61P7/08 ,  A61P19/02 ,  A61P25/28 ,  A61P31/04 ,  C07C311/19 ,  C07C311/29 ,  C07C311/46 ,  C07C323/67 ,  C07D307/12 ,  C07C311/01 ,  A61K31/18

    Abstract: Compounds of formula (I), (II) and (III) are inhibitors of interleukin-1'beta' converting enzyme. The compounds can be used in a medicament to treat stroke, inflammatory diseases, septic shock, reperfusion injury, Alzheimer's disease and shigellosis. In formula (I), (II) and (III); R1 is hydrogen, C1-C6alkyl, or benzyl; R2 is -CHO, -CORa, or -CN, Ra is independently hydrogen or C1-C6aIkyl; X is a bond, CH2, CHR5, NH, NR5, or O; R5 is hydrogen, C1-C6alkyl, aryl, or -(CH2)naryl (each n is independently 0 to 5); m is 1 or 2. In formula (I) R3 is optionally substituted-aryl, optionally substituted-heteroaryl, optionally substituted cycloalkyl, or optionally substituted heterocycle; R4 is absent, optionally substituted-aryl, C1-C8alkyl, optionally substituted heteroaryl, C1-C6alkyl, optionally substituted-cycloalkyl or optionally substituted heterocycloalkyl; Y is absent, NR5, CO, S, O, SO2, O(CHR5)n-, CHR5, NR5CO, CONR5, OCHR5, CHR5O, SCHR5, CHR5S, SO2NR5, C1-C6alkyl, NR5SO2, CH2CHR5, CHR5CH2, COCH2, or CH2CO. In formula (II); Each Z is independently hydrogen, an optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or an optionally substituted heterocycle group that is fused to the phenyl group that contains Z as a substituent; Y is a bond, NR5, CO, S, O, SO2, CHR5, NR5CO, CONR5, OCHR5, -O(CHR5)n-, CHR5O, SCHR5, CHR5S, SO2NR5, NR5S02, CH2CHR5, CHR5CH2, COCH2, or CH2CO; Rb, Rc, Rd, and Re are each independently hydrogen, C1-C6alkyl, C1-C6alkoxy, -OH, C1-C6thioalkoxy, halogen, trifluoromethyl, dialkylamino, -NO2, -CN, -CF3, -CO2alkyl, -SO3H, -CHO, -COalkyl, -CONH-alkyl, -CONHRq, -CON(alkyl)2, -(CH2)n-NH2, -(CH2)n-NH-alkyl, -NHRq, -NHCORq, -(CH2)nOH, -(CH2)nCONH2, or (CH2)nCO2H, (wherein Rq is hydrogen or C1-C6alkyl). In Formula (III): Each Z is absent or independently hydrogen, an optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or an optionally substituted heterocycle group that is fused to the phenyl group that contains Z as a substituent; and Rf, Rg, are each independently hydrogen, C1 -C6alkyl, hydroxy, halogen, trifluoromethyl, dialkylamino, -NO2, -CN, -CO2H, -C02alkyl, -S03H, -CHO, -COalkyl, -CONH2, -CONH(CH2)naryl, -CONH(CH2)n-substituted-aryl, -CONH-alkyl, -CONHRq, -CON(alkyl)2, -(CH2)n-NH2, -(CH2)n-NH-alkyl, -NHRq, -NHCORq, -OR9, -SR9, or -(CH2)naryl, (wherein Rq is hydrogen or C1-C6alkyl).

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