Patent Evaluation: Mercaptoacetylamides derivatives capable of inhibiting enkephalinase and ACE

Summary

Novelty: Novel 2-substituted indane-2-mercaptoacetylaraides are claimed as inhibitors of angiotensin-converting enzyme and enkephalinase.

Biology: Inhibition of enkephalinase was measured by the fluorometric methods of Florentin et al. (Anal. Biochem. (1984) 141:62–69) and the enzymatic activity of ACE was monitored using a spectrophotometric substrate (Anal. Biochem. (1979) 95:540–548). The Ki (nM) for enkephalinase inhibition varied from < 0.2 to 4. The corresponding figures for ACE inhibition were < 7 and < 500.

Chemistry: Synthesis of forty compounds is described. Seven compounds are specifically claimed and four of these are preferred.