3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors

Regis Leung-Toung; Tim F Tam; Jolanta M Wodzinska; Yanqing Zhao; Jayme Lowrie; Craig D Simpson; Khashayar Karimian; Michael Spino

doi:10.1021/jm049221w

3-Substituted imidazo[1,2-d][1,2,4]-thiadiazoles: a novel class of factor XIIIa inhibitors

J Med Chem. 2005 Apr 7;48(7):2266-9. doi: 10.1021/jm049221w.

Authors

Regis Leung-Toung¹, Tim F Tam, Jolanta M Wodzinska, Yanqing Zhao, Jayme Lowrie, Craig D Simpson, Khashayar Karimian, Michael Spino

Affiliation

¹ Department of Medicinal Chemistry, Apotex Research Inc., 400 Ormont Drive, Toronto, ON M9L 1N9, Canada.

PMID: 15801818
DOI: 10.1021/jm049221w

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.

MeSH terms

Animals
Factor XIII / antagonists & inhibitors*
Factor XIII / chemistry
Fibrinolytic Agents / chemical synthesis*
Fibrinolytic Agents / chemistry
Fibrinolytic Agents / pharmacology
Guinea Pigs
Humans
Imidazoles / chemical synthesis*
Imidazoles / chemistry
Imidazoles / pharmacology
In Vitro Techniques
Kinetics
Structure-Activity Relationship
Thiadiazoles / chemical synthesis*
Thiadiazoles / chemistry
Thiadiazoles / pharmacology

Substances

Fibrinolytic Agents
Imidazoles
Thiadiazoles
Factor XIII