title: Discovery and synthesis of a novel series of quinoline-based thrombin receptor (PAR-1) antagonists.
abstract: The design, synthesis, and SAR studies of a structurally novel series of highly potent thrombin receptor (PAR-1) antagonists are described. Compound 30 is a highly potent thrombin receptor antagonist (IC(50)=6.3 nM), a related compound 36 showing efficacy in a monkey ex vivo study.
authors.affiliation: Central Nervous System and Cardiovascular Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. martin.clasby@spcorp.com
authors.forename: Martin C
authors.initials: MC
authors.lastname: Clasby
authors.forename: Samuel
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: Michael
authors.initials: M
authors.lastname: Czarniecki
authors.forename: Dario
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: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Hsingan
authors.initials: H
authors.lastname: Tsai
authors.forename: Yan
authors.initials: Y
authors.lastname: Xia
authors.forename: Ho-Sam
authors.initials: HS
authors.lastname: Ahn
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Agans-Fantuzzi
authors.forename: George
authors.initials: G
authors.lastname: Boykow
authors.forename: Madhu
authors.initials: M
authors.lastname: Chintala
authors.forename: Carolyn
authors.initials: C
authors.lastname: Foster
authors.forename: Matthew
authors.initials: M
authors.lastname: Bryant
authors.forename: Janice
authors.initials: J
authors.lastname: Lau
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006575:Heterocyclic Compounds, 3-Ring / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008252:Macaca fascicularis; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000737:chemistry*; D018179:Receptors, Thrombin / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C505164:4-(5-(3-trifluoromethylphenyl)pyridin-2-yl)ethenyl-3-methyldecahydronaphtho(2,3-c)furan-1(3H)-one; D005343:Fibrinolytic Agents; D006575:Heterocyclic Compounds, 3-Ring; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D011804:Quinolines; D018179:Receptors, Thrombin; C037219:quinoline