title: 5,5-trans lactone-containing inhibitors of serine proteases: identification of a novel, acylating thrombin inhibitor.
abstract: Synthesis of a variety of 5,5-trans fused lactones, related to compounds found in extracts of Lantana camara, has provided a series of novel acylating inhibitors of human thrombin, trypsin, chymotrypsin and human leucocyte elastase. The most effective thrombin inhibitor is 7 with an IC50 of 130 nM and a Kobs/[1] of 4,000 M-1 s-1.
authors.affiliation: Department of Medicinal Chemistry, GlaxoWellcome Research and Development, Stevenage, Herts., U.K. hf3736@glaxowellcome.co.uk
authors.forename: H
authors.initials: H
authors.lastname: Finch
authors.forename: N A
authors.initials: NA
authors.lastname: Pegg
authors.forename: J
authors.initials: J
authors.lastname: McLaren
authors.forename: A
authors.initials: A
authors.lastname: Lowdon
authors.forename: R
authors.initials: R
authors.lastname: Bolton
authors.forename: S J
authors.initials: SJ
authors.lastname: Coote
authors.forename: U
authors.initials: U
authors.lastname: Dyer
authors.forename: J G
authors.initials: JG
authors.lastname: Montana
authors.forename: M R
authors.initials: MR
authors.lastname: Owen
authors.forename: M
authors.initials: M
authors.lastname: Dowle
authors.forename: D
authors.initials: D
authors.lastname: Buckley
authors.forename: B C
authors.initials: BC
authors.lastname: Ross
authors.forename: C
authors.initials: C
authors.lastname: Campbell
authors.forename: C
authors.initials: C
authors.lastname: Dix
authors.forename: C
authors.initials: C
authors.lastname: Mooney
authors.forename: C
authors.initials: C
authors.lastname: Man-Tang
authors.forename: C
authors.initials: C
authors.lastname: Patel
mesh_terms: D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D007783:Lactones / Q000138:chemical synthesis*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D007783:Lactones; D015842:Serine Proteinase Inhibitors; D013917:Thrombin