title: 3-Amino-2-hydroxyamides and related compounds as inhibitors of methionine aminopeptidase-2.
abstract: 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).
authors.affiliation: Abbott Laboratories, Global Pharmaceutical Research and Development, Cancer Research, 100 Abbott Park Road, Abbott Park, IL 60064, USA. george.sheppard@abbott.com
authors.forename: George S
authors.initials: GS
authors.lastname: Sheppard
authors.forename: Jieyi
authors.initials: J
authors.lastname: Wang
authors.forename: Megumi
authors.initials: M
authors.lastname: Kawai
authors.forename: Nwe Y
authors.initials: NY
authors.lastname: BaMaung
authors.forename: Richard A
authors.initials: RA
authors.lastname: Craig
authors.forename: Scott A
authors.initials: SA
authors.lastname: Erickson
authors.forename: Linda
authors.initials: L
authors.lastname: Lynch
authors.forename: Jyoti
authors.initials: J
authors.lastname: Patel
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.forename: Xenia B
authors.initials: XB
authors.lastname: Searle
authors.forename: Pingping
authors.initials: P
authors.lastname: Lou
authors.forename: Chang
authors.initials: C
authors.lastname: Park
authors.forename: Ki H
authors.initials: KH
authors.lastname: Kim
authors.forename: Jack
authors.initials: J
authors.lastname: Henkin
authors.forename: Richard
authors.initials: R
authors.lastname: Lesniewski
mesh_terms: D000577:Amides / Q000737:chemistry* / Q000494:pharmacology*; D000626:Aminopeptidases / Q000037:antagonists & inhibitors*; D001665:Binding Sites / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D008715:Methionine / Q000187:drug effects; D008954:Models, Biological; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D008715:Methionine; D000626:Aminopeptidases; C106541:methionine aminopeptidase 2; D008666:Metalloendopeptidases