title: Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors. 2. Exploring interactions at the proximal (S2) binding site.
abstract: In an effort to increase the thrombin inhibitory activity of a novel series of inhibitors (i.e., 1a), substituents were incorporated at the C-3" position of the C-3 aryl ring (2). Consistent with the X-ray crystallography studies, small hydrophobic groups at the C-3" site (Br and Me) enhanced thrombin inhibitory activity by 8-fold. However, a few more hydrophilic substituents (NO2 and OMe) also enhanced the potency of the series. The biological results are discussed in terms of molecular modeling studies.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: D J
authors.initials: DJ
authors.lastname: Sall
authors.forename: S L
authors.initials: SL
authors.lastname: Briggs
authors.forename: N Y
authors.initials: NY
authors.lastname: Chirgadze
authors.forename: D K
authors.initials: DK
authors.lastname: Clawson
authors.forename: D S
authors.initials: DS
authors.lastname: Gifford-Moore
authors.forename: V J
authors.initials: VJ
authors.lastname: Klimkowski
authors.forename: J R
authors.initials: JR
authors.lastname: McCowan
authors.forename: G F
authors.initials: GF
authors.lastname: Smith
authors.forename: J H
authors.initials: JH
authors.lastname: Wikel
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D008956:Models, Chemical; D008958:Models, Molecular; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D015842:Serine Proteinase Inhibitors; D013876:Thiophenes; C088015:benzothiophene; D013917:Thrombin