Substituted oxobutyric acid derivative as matrix metalloprotease inhibitor

本发明提供了药物组合物和治疗某些与基质金属蛋白酶有关的疾病的方法，该方法包括给予一定量的有效抑制至少一种基质金属蛋白酶的本发明化合物或组合物，以达到所希望的效果。本发明的化合物是通式(I)中任一种：其中y是0，2或3，r是0-6，Z是(CH#-[2])#-[7]或(CH#-[2])#-[e]-C#-[6]H#-[4]-(CH#-[2])#-[f]，其中e是0-1，f是0-5，且R#+[15]是-H、-Cl、-OMe或(a)，(b)，其中n是0-4，R#+[17]是C#-[2]H#-[5]、烯丙基、苄基，和R#+[16]是(c)，其中t是0-2，x是0-4，且R#+[4]是下列一种：卤离子、1-6个碳的烷基、OR、NR#-[2]、NO#-[2](R＝H或1-6个碳的烷基)。∴∴∴ The present invention provides pharmaceutical compositions and methods for treating certain conditions comprising administering an amount of a compound or composition of the invention which is effective to inhibit the activity of at least one matrix metalloprotease, resulting in achievement of the desired effect. The compounds of the present invention are either of generalized formula (I) wherein y is 0, 2, or 3, r is 0-6, Z is (CH2)7 or (CH2)e-C6H4-(CH2)f, wherein e is 0-1 and f is 1-6, and R is -H, -Cl, -OMe or (a), (b) wherein n is 0-4, R is C2H5, allyl, benzyl, and R is (c) wherein t is 0-1, x is 0-4, and R is one of the following: halide, alkyl of 1-6 carbons, OR, NR2, NO2 (R = H or alkyl of 1-6 carbons). These compounds are useful for inhibiting matrix metalloproteases and, therefore, combating conditions to which MMP's contribute, such as osteoarthritis, rheumatoid arthritis, septic arthritis, periodontal disease, corneal ulceration, proteinuria, aneurysmal aortic disease, dystrophobic epidermolysis, bullosa, conditions leading to inflammatory responses, osteopenias mediated by MMP activity, tempero mandibular joint disease, demyelating diseases of the nervous system, tumor metastasis or degenerative cartilage loss following traumatic joint injury, and coronary thrombosis from atherosclerotic plaque rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.