3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors.
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.
Leung-Toung
Regis
R
Department of Medicinal Chemistry, Apotex Research Inc., 400 Ormont Drive, Toronto, ON M9L 1N9, Canada.
Tam
Tim F
TF
Wodzinska
Jolanta M
JM
Zhao
Yanqing
Y
Lowrie
Jayme
J
Simpson
Craig D
CD
Karimian
Khashayar
K
Spino
Michael
M
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
D005343:Fibrinolytic Agents; D007093:Imidazoles; D013830:Thiadiazoles; D005176:Factor XIII