Synthesis and creatine kinase inhibitory activity of non-hydrolyzable analogs of phosphocreatine

The first hydrolytically stable phosphocreatine (CrP) analogs with a CH2---P isostere in place of the NH---P linkage have been synthesized and found to inhibit creatine kinase (CK) with potencies in the low mM range. The closest structural analog of CrP, 2, was found to have a Ki (1.4 mM) near the Km of CrP (2.5 mM), making it the most potent known reversible inhibitor of CK.