Patent Evaluation: Phosphonopeptides with collagenase inhibiting activity

Abstract

Novelty: Novel phosphonopeptides are disclosed as collagenase inhibitors. They may be used to treat arthritis and localized connective tissue breakdown (into which they can penetrate easily due to their small molecular size).

Biology: Collagenase inhibition was assayed according to the method of Cawston and Barrett (Anal. Biochem. (1979) 99:340-345). IC₅₀ values = 2.3 × 10^-6 - 1.3 × 10^-8 M for eleven compounds tested.

Chemistry: Seventy examples of syntheses of the compounds and intermediates by standard techniques are provided. Characterization is by nmr, ms, optical rotation and elemental analysis. A disclosed compound is N-[N-(1 -phosphono-3-(1,8-naphthalenedicarboxamido)propyl)-(S)-leucy 11-(S)-pheny lalanine-N-methylamide.