title: Design, synthesis and SAR of a series of 1,3,5-trisubstituted benzenes as thrombin inhibitors.
abstract: A novel 1,3,5-trisubstituted benzamide thrombin inhibitor template was designed via hybridization of a known aminopyridinoneacetamide and a known 1,3,5-trisubstituted phenyl ether. Optimization of this lead afforded a novel potent series of biaryl 1,3,5-trisubstituted benzenes with excellent functional anticoagulant potency.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. richard_isaacs@verizon.net
authors.forename: Richard C A
authors.initials: RC
authors.lastname: Isaacs
authors.forename: Christina L
authors.initials: CL
authors.lastname: Newton
authors.forename: Kellie J
authors.initials: KJ
authors.lastname: Cutrona
authors.forename: Swati P
authors.initials: SP
authors.lastname: Mercer
authors.forename: Linda S
authors.initials: LS
authors.lastname: Payne
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Stauffer
authors.forename: Peter D
authors.initials: PD
authors.lastname: Williams
authors.forename: Jacquelynn J
authors.initials: JJ
authors.lastname: Cook
authors.forename: Julie A
authors.initials: JA
authors.lastname: Krueger
authors.forename: S Dale
authors.initials: SD
authors.lastname: Lewis
authors.forename: Bobby J
authors.initials: BJ
authors.lastname: Lucas
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Lyle
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Lynch
authors.forename: Daniel R
authors.initials: DR
authors.lastname: McMasters
authors.forename: Adel M
authors.initials: AM
authors.lastname: Naylor-Olsen
authors.forename: Maria T
authors.initials: MT
authors.lastname: Michener
authors.forename: Audrey A
authors.initials: AA
authors.lastname: Wallace
mesh_terms: D000991:Antithrombins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001554:Benzene / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D000991:Antithrombins; D013917:Thrombin; D001554:Benzene