title: Design and synthesis of monocyclic beta-lactams as mechanism-based inhibitors of human cytomegalovirus protease.
abstract: Mechanism based inhibitors of HCMV protease have been designed based on the monocyclic beta-lactam nucleus, which have been shown to acylate the viral enzyme in a time dependent manner. SAR in a series of monocyclic beta-lactam N-ureas, has defined the size and relative stereochemistry of the C-3 substituent producing a low micromolar inhibitor 17b with good aqueous stability and selectivity over the mammalian serine proteases.
authors.affiliation: Department of Enzyme Medicinal Chemistry II, Glaxo Wellcome Research and Development, Medicines Research Centre, Stevenage, Herts, UK. adb3028@ggr.co.uk
authors.forename: A D
authors.initials: AD
authors.lastname: Borthwick
authors.forename: G
authors.initials: G
authors.lastname: Weingarten
authors.forename: T M
authors.initials: TM
authors.lastname: Haley
authors.forename: M
authors.initials: M
authors.lastname: Tomaszewski
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.forename: J
authors.initials: J
authors.lastname: Bedard
authors.forename: H
authors.initials: H
authors.lastname: Jin
authors.forename: L
authors.initials: L
authors.lastname: Yuen
authors.forename: T S
authors.initials: TS
authors.lastname: Mansour
mesh_terms: D004355:Drug Stability; D006801:Humans; D007536:Isomerism; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D011480:Protease Inhibitors; D047090:beta-Lactams; D012697:Serine Endopeptidases; C071910:assemblin