| 摘要 |
The present invention relates to compounds that exhibit inhibitory activity against matrix metalloproteases ("MMPs"). Because MMPs are known to play a role in tissue degradation, the compounds of the present invention may be useful in preventing or treating diseases associated with excess MMP activity. In particular, the compounds have a structure according to formula (I), wherein (A) (1) (a) R1 is hydrogen; alkyl; heteroalkyl; alkenyl; a heterocyclic ring; a carbocyclic ring; alkoxy; carbocycle-alkyl; heterocyclealkyl; carbocycle-heteroalkyl; or heterocycle-heteroalkyl; and (b) R2 is hydrogen; hydroxy; alkyl; alkenyl; alkynyl; heteroalkyl; a heterocyclic ring; a carbocyclic ring; carbocycle-alkyl; heterocycle-alkyl; or -OR, where R is alkyl, alkenyl, or carbocycle-alkyl; or (2) R1 and R2 together form a cycloalkyl ring having from 3 to 8 ring atoms; (B) R3 is hydrogen; alkyl; or carbocycle-alkyl; (C) R4 is: (1) alkyl; (2) carbocyle-alkyl; (3) -X-C(=Y)-Z-R5 or -X-CH2-Z-R5, where (a) X is covalent bond or alkyl; (b) Y is O, S, or NH; (c) Z is O, S, or NH; and (d) R5 is hydrogen; alkyl; alkenyl; carbocyclealkyl; or aryl; or (4) -SO2-R6, where R6 is alkyl, carbocycle-alkyl, heterocycle-alkyl, or aryl; and (D) Q is -¢-C(R7)2-!-n, where (1) n is the integer 2, 3, or 4; and (2) each R7 is independently hydrogen or alkyl so the Q-containing heterocycle is saturated; or the R7 moiety on two adjacent carbon atoms is a covalent bond such that the Q-containing heterocycle in Formula (I) is unsaturated; or a pharmaceutically-acceptable salt; or biohydrolyzable alkoxyamide, acyloxyamide, or imide thereof. The invention also relates to pharmaceutical compositions comprising these compounds, and methods for preventing or treating diseases associated with unwanted MMP activity using the compounds and compositions.
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