title: Himbacine derived thrombin receptor (PAR-1) antagonists: structure-activity relationship of the lactone ring.
abstract: The structure-activity relationship (SAR) of the lactone ring of himbacine derived thrombin receptor (PAR-1) antagonists (e.g., 2-5) is described. The effect of the lactone carbonyl group on binding to PAR-1 is dependent on the substitution pattern of the pyridine ring. A stereoselective intramolecular Michael addition reaction to the vinyl pyridine group was observed for these pyridine analogs of himbacine in basic conditions at elevated temperature.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. yan.xia@spcorp.com
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Samuel
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: Tze-Ming
authors.initials: TM
authors.lastname: Chan
authors.forename: Michael
authors.initials: M
authors.lastname: Czarniecki
authors.forename: Darío
authors.initials: D
authors.lastname: Doller
authors.forename: Keith
authors.initials: K
authors.lastname: Eagen
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Hsingan
authors.initials: H
authors.lastname: Tsai
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.forename: Ho-Sam
authors.initials: HS
authors.lastname: Ahn
authors.forename: George C
authors.initials: GC
authors.lastname: Boykow
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McPhail
mesh_terms: D000470:Alkaloids / Q000737:chemistry*; D005663:Furans / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D044463:Receptor, PAR-1 / Q000378:metabolism; D013329:Structure-Activity Relationship; D010975:Platelet Aggregation Inhibitors
chemical_list: D000470:Alkaloids; D005663:Furans; D007783:Lactones; D009281:Naphthalenes; D010880:Piperidines; D044463:Receptor, PAR-1; C048172:himbacine; D010975:Platelet Aggregation Inhibitors