| 摘要 |
A 2-oxo-2H-quinoline or 2-oxo-1,4-dihydro-2H- quinazoline derivative has the formula (I) wherein: R1 is hydrogen, CN, CHN2, R or -CH2Y; R is an optionally substituted aliphatic group, aryl group, aralkyl group or non-aromatic heterocyclic group; Y is an electronegative leaving group, -OR, -SR, -OC(=O)(R) or -OPO(R8)(R9); R8 and R9 are independently R or OR; R2 is CO2H, CH2CO2H or esters, amides or isosteres thereof; R3 is hydrogen or alkyl; Ring A is fused Ring B and Ring B is an optionally saturated five to seven membered ring containing zero to three heteroatoms; X3 in Ring A is nitrogen or carbon wherein X3 with suitable valence may bear a substituent; each carbon with suitable valence in Ring A and Ring B is independently substituted by hydrogen, halo, R, OR, SR, OH, NO2, CN, NH2, NHR, N(R)2, NHCOR, NHCONHR, NHCON(R)2, NRCOR, NHCO2R, CO2R, CO2H, COR, CONHR, CON(R)2, S(O)2R, SONH2, S(O)R, SO2NHR, NHS(O)2R, =O, =S, =NNHR, =NNR2, =N-OR, =NNHCOR, =NNHCO2R, =NNHSO2R, or =NR and each substitutable nitrogen in Ring A is substituted by hydrogen, R, COR, S(O)2R, or CO2R; provided that when X3 is a carbon, a substituent on X3 is attached by an atom other than nitrogen. A pyridine derivative has formula (IA) wherein: R1 is CH2F, R2 is CO2H, and a) R3 to R7 are H; b) R3 is Me and R4 to R7 are H; c) R4 is Me and R3 and R5 to R7 are H; d) R6 is Ph and R3, R3 to R5 and R7 are H or e) R4 is Et, R7 is Ph and R3, R3, R5 and R6 are H. The compounds are useful as caspase inhibitors and are useful for treating diseases where caspase activity is implicated such as an IL-1 mediated disease, an apoptosis mediated disease, an inflammatory disease, an autoimmune disease, a destructive bone disorder or a proliferative disorder.
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