Synthesis and biological evaluation of novel piperidine carboxamide derived calpain inhibitors

Calpain inhibitors which are derived from piperidine carboxamides in the P- 2 legion were prepared and evaluated for mu-calpain inhibition. In particul ar, the keto amides 11f and 11j have K-i of 30 and 9 nM and display a more than 100-fold selectivity over the closely related cysteine protease cathep sin B. Furthermore, these compounds inhibit NMDA induced convulsions in mic e indicating that calpain inhibition in brain results in some anticonvulsiv e properties. (C) 2000 Elsevier Science Ltd. All rights reserved.