Synthesis and evaluation of potent, highly-selective, 3-aryl-piperazinone inhibitors of protein geranylgeranyltransferase-I

…, D Carrico, V Thai, M Blaskovich, C Bucher…

Index: Peng, Hairuo; Carrico, Dora; Thai, Van; Blaskovich, Michelle; Bucher, Cynthia; Pusateri, Erin E.; Sebti, Said M.; Hamilton, Andrew D. Organic and Biomolecular Chemistry, 2006 , vol. 4, # 9 p. 1768 - 1784

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Citation Number: 42

Abstract

A series of compounds based on the carboxyl-terminal CAAL sequence of PGGTase-I substrates was designed and synthesized. Using piperazin-2-one as a semi-rigid scaffold, we have introduced critical pharmacophores in a well-defined arrangement to mimic the CAAL sequence. High potency and exceptional selectivity were obtained for inhibition of PGGTase-I with structures such as 45 and 70. Potency of this series of GGTIs was ...