3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2

Substituted 3-amino-2-hydroxyamides and related hydroxyamides and acylhydrazines were identified as inhibitors of human methionine aminopeptidase-2 (MetAP2). Examination of substituents through parallel synthesis and iterative structure-based design allowed the identification of potent inhibitors with good selectivity against MetAP1. Diacylhydrazine 3t (A-357300) was identified as an analogue displaying inhibition of methionine processing and cellular proliferation in human microvascular endothelial cells (HMVEC).