title: Synthesis of indole derived protease-activated receptor 4 antagonists and characterization in human platelets.
abstract: Protease activated receptor-4 (PAR4) is one of the thrombin receptors on human platelets and is a potential target for the management of thrombotic disorders. We sought to develop potent, selective, and novel PAR4 antagonists to test the role of PAR4 in thrombosis and hemostasis. Development of an expedient three-step synthetic route to access a novel series of indole-based PAR4 antagonists also necessitated the development of a platelet based high-throughput screening assay. Screening and subsequent structure activity relationship analysis yielded several selective PAR4 antagonists as well as possible new scaffolds for future antagonist development.
authors.affiliation: Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.
authors.forename: Summer E
authors.initials: SE
authors.lastname: Young
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Duvernay
authors.forename: Michael L
authors.initials: ML
authors.lastname: Schulte
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
authors.forename: Heidi E
authors.initials: HE
authors.lastname: Hamm
mesh_terms: D000328:Adult; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006801:Humans; D007191:Indazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D007211:Indoles / Q000737:chemistry*; D008297:Male; D015539:Platelet Activation / Q000187:drug effects; D018179:Receptors, Thrombin / Q000037:antagonists & inhibitors*
chemical_list: C412964:1-benzyl-3-(ethoxycarbonylpheny)-indazole; D005343:Fibrinolytic Agents; D007191:Indazoles; D007211:Indoles; D018179:Receptors, Thrombin; C030374:indole; C112908:protease-activated receptor 4