INHIBITION OF MATRIX METALLOPROTEASES BY ACETYLENE CONTAINING COMPOUNDS

摘要

Matrix metalloprotease inhibiting compounds, pharmaceutical compositions thereof and a method of disease treatment using such compounds are presented. The compounds of the invention have the generalized formula (I) where R<15> is selected from the group comprising: HOCH2, MeOCH2, (n-Pr)2NCH2, CH3CO2CH2, EtOCO2CH2, HO(CH2)2, CH3CO2(CH2)2, HO2C(CH2)2, OHC(CH2)3, HO(CH2)4, Ph, 3-HO-Ph, and PhCH2OCH2; and R<16> is (a) or (b). 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 athrosclerotic plate rupture. The present invention also provides pharmaceutical compositions and methods for treating such conditions.