SUBSTITUTED PHOSPHINIC ACID CONTAINING PEPTIDYL DERIVATIVES AS ANTIDEGENERATIVE AGENTS
Novel phosphinic acid-containing peptidyl compounds of formula I are found to be useful inhibitors of matrix metalloendoproteinase-mediated diseases including osteoarthritis, rheumatoid arthritis, septic arthritis, tumor invasion in certain cancers, perio
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(2008/06/13)
Phosphinic acid inhibitors of matrix metalloproteinases
The matrix metalloproteinase stromelyin-1 (MMP-3) is inhibited more strongly by peptidyl phosphinic acid 7 than by its corresponding phosphonamidate and phosphonate analogs. Extending a benzyl group at P1' to a phenylethyl group in 8 further increases the potency (K(i) = 1.4 nM). Enhanced potency with an extended substituent into the P3 region was observed.