SYNTHESIS AND CREATINE-KINASE INHIBITORY ACTIVITY OF NONHYDROLYZABLE ANALOGS OF PHOSPHOCREATINE

The first hydrolytically stable phosphocreatine (CrP) analogs with a C H2-P isostere in place of the NH-P linkage have been synthesized and f ound to inhibit creatine kinase (CK) with potencies in the low mM rang e. The closest structural analog of CrP, 2, was found to have a K-i (1 .4 mM) near the K-m of CrP (2.5 mM), making it the most potent known r eversible inhibitor of CK. (C) 1997 Elsevier Science Ltd.