64466-48-4Relevant articles and documents
Discovery of Potent Protease-Activated Receptor 4 Antagonists with in Vivo Antithrombotic Efficacy
Miller, Michael M.,Banville, Jacques,Friends, Todd J.,Gagnon, Mark,Hangeland, Jon J.,Lavallée, Jean-Fran?ois,Martel, Alain,O'Grady, Harold,Rémillard, Roger,Ruediger, Edward,Tremblay, Fran?ois,Posy, Shana L.,Allegretto, Nick J.,Guarino, Victor R.,Harden, David G.,Harper, Timothy W.,Hartl, Karen,Josephs, Jonathan,Malmstrom, Sarah,Watson, Carol,Yang, Yanou,Zhang, Ge,Wong, Pancras,Yang, Jing,Bouvier, Michel,Seiffert, Dietmar A.,Wexler, Ruth R.,Lawrence, R. Michael,Priestley, E. Scott,Marinier, Anne
, p. 7400 - 7416 (2019/08/26)
In an effort to identify novel antithrombotics, we have investigated protease-activated receptor 4 (PAR4) antagonism by developing and evaluating a tool compound, UDM-001651, in a monkey thrombosis model. Beginning with a high-throughput screening hit, we identified an imidazothiadiazole-based PAR4 antagonist chemotype. Detailed structure-activity relationship studies enabled optimization to a potent, selective, and orally bioavailable PAR4 antagonist, UDM-001651. UDM-001651 was evaluated in a monkey thrombosis model and shown to have robust antithrombotic efficacy and no prolongation of kidney bleeding time. This combination of excellent efficacy and safety margin strongly validates PAR4 antagonism as a promising antithrombotic mechanism.
Comparison of radioprotective activities of similar substituted derivatives of benzofurane and 2H-chromene
Fatome,Andrieu,Laval,et al.
, p. 383 - 384 (2007/10/10)
-
