5-phenyl-pentanoic acid derivatives as matrix metalloproteinase inhibitors for the treatment of asthma and other diseases

Abstract

The present invention relates to Compounds having the structure of Formula I: wherein n is an integer from 1 to 5; Ris optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, alkoxy, aryloxy, alkenyloxy or alkynyloxy; Ris alkenyl, allcynyl, aryl, heterocyclyl, heteroaryl, cycloalkyl, NRR, —NHC(═Y)R, —NHC(═Y)NRR, —NHC(═O)OR, —NHSOR, C(═Y)NRR, C(═O)OR[wherein Y is oxygen or sulphur], OR, —O(C═O)NRR, O-acyl, S(O)R, —SON(R), cyano, amidino or guanidino [wherein Ris alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocyclyl, heteroaryl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl and m is an integer 0-2; Ris hydrogen or R; Ris Ror —SON(R)and Ris hydrogen, alkyl, cycloalkyl, aralkyl, heteroarylalkyl, heterocyclylalkyl or cycloalkylalkyl]; Ris hydrogen, fluorine, alkyl, cycloalkylalkyl or aralkyl; A is OH, OR, —OC(═O)NRR, O-acyl, NH, NRR, —NHC(═Y)R, —NHC(═Y)NRR, —NHC(═O)OR, —NHSOR, and to processes for the synthesis of the same. This invention also relates to pharmacological compositions containing the compounds of the present invention, and methods of treating asthma, rheumatoid arthritis, COPD, rhinitis, osteoarthritis, psoriatic arthritis, psoriasis, pulmonary fibrosis pulmonary inflammation, acute respiratory distress syndrome, perodontitis, multiple sclerosis, gingivitis, atherosclerosis, neointimal proliferation, which leads to restenosis and ischemic heart failure, stroke, renal diseases, tumor metastasis, and other inflammatory disorders characterized by over-expression and over-activation of an matrix metalloproteinase, using the compounds.