title: 3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors.
abstract: A new class of selective FXIIIa inhibitors with a bicyclic [1,2,4]-thiadiazole pharmacophore is described. At 160 muM, compound 8 caused 50% reduction in fibrin gamma-chain cross-linking and suppressed the polymerization of alpha chains in platelet-depleted human plasma clots. Fibrinolysis rates in response to tissue plasminogen activator were directly proportional to the concentration of 8 in plasma at the time of clotting.
authors.affiliation: Department of Medicinal Chemistry, Apotex Research Inc., 400 Ormont Drive, Toronto, ON M9L 1N9, Canada.
authors.forename: Regis
authors.initials: R
authors.lastname: Leung-Toung
authors.forename: Tim F
authors.initials: TF
authors.lastname: Tam
authors.forename: Jolanta M
authors.initials: JM
authors.lastname: Wodzinska
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jayme
authors.initials: J
authors.lastname: Lowrie
authors.forename: Craig D
authors.initials: CD
authors.lastname: Simpson
authors.forename: Khashayar
authors.initials: K
authors.lastname: Karimian
authors.forename: Michael
authors.initials: M
authors.lastname: Spino
mesh_terms: D000818:Animals; D005176:Factor XIII / Q000037:antagonists & inhibitors* / Q000737:chemistry; D005343:Fibrinolytic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006168:Guinea Pigs; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D005343:Fibrinolytic Agents; D007093:Imidazoles; D013830:Thiadiazoles; D005176:Factor XIII