| 摘要 |
PURPOSE: Provided is certain novel 3-mercaptoacetylamino-1,5-substituted-2-oxo-azepan derivatives useful as inhibitors of matrix metalloprotease. Pharmaceutical compositions containing the compounds as well as methods of treating various disease states responding to inhibition of matrix metalloprotease are also provided. CONSTITUTION: Provided is a compound of the formula 1 wherein R1 is C1-C6 alkyl, a W -(CH2)m- group, or a Q-Z-(CH2)m- group wherein W is phthalimido; Z is a bond or is oxy, NR6, C(O)NR6, NR6C(O), NHC(O)NR6, OC(O)NR6, HNC(O)O, or SO2NR6; Q is hydrogen, or a Y-(CH2)n- group wherein Y is hydrogen, C6-C10 aryl, C3-C9 heteroaryl, -C(O)OR6, -N(R6)2, morpholino, piperidino, pyrrolidino, or isoindolyl; R2 is C1-C4 alkyl, a -(CH2)p-(C3-Cg)heteroaryl group, or a -(CH2)p-Ar1 group wherein Ar1 is phenyl or naphthyl optionally substituted with a substituent selected from the group consisting of halogen, C1-C4 alkyl, -OR7, -N(R6)2, S02N(R6)2 or -NO2; R3 is hydrogen, C1-C6 alkyl, -CH2SCH2NHCOCH3, a -(CH2)p-A group, a -(CH2)m-B group or a -CH2-D-R7 group wherein A is C6-Clo aryl, C3-C9 heteroaryl, or cyclohexyl; B is -N(R7)2, guanidino, nitroguanidino, -C(O)OR6 or -C(O)NR6; and D is oxy or thio; R4 is hydrogen or a -(CH2)m-S(O)pX'(R6)2 group; R5 is hydrogen, C1-C6 alkyl or R4 and Rs taken together with the nitrogen atom to which they are attached form piperidino, pyrrolidino, or isoindolyl; R6 is hydrogen or C1-C6 alkyl; R7 is hydrogen, CI-C4 alkyl, or a -(CH2)p-Ar2 group wherein Ar2 is phenyl or naphthyl optionally substituted with a substituent selected from the group consisting of halogen, C1-C4 alkyl, -OR7, -N(R6)2, SO2N(R6)2 or -NO2; R8 is hydrogen, -C(O)R7, a -C(O)-(CH2)q-K group or a -S-G group
|
