59445-59-9Relevant academic research and scientific papers
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.
IMIDAZOTHIADIAZOLE DERIVATIVES AS PROTEASE ACTIVATED RECEPTOR 4 (PAR4) INHIBITORS FOR TREATING PLATELET AGGREGATION
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Paragraph 00143, (2013/11/18)
The present invention provides imidazothiadiazole compounds of Formula (I) wherein A, B, D, Rx, R1, R2, R3, X1, X2 and s are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt or solvate form thereof, wherein all of the variables are as defined herein. These compounds are inhibitors of platelet aggregation and thus can be used as medicaments.
Straightforward synthesis of dihydrobenzofurans and benzofurans from arynes
Yoshioka, Eito,Tanaka, Hidekazu,Kohtani, Shigeru,Miyabe, Hideto
, p. 3938 - 3941 (2013/09/02)
Synthesis of dihydrobenzofurans was achieved by a route involving the insertion of arynes into formamides followed by trapping with zinc enolates of α-chlorinated methines. Benzofurans were generated from dihydrobenzofurans having a ketone group via the addition of an ethyl anion, the retro-aldol type reaction, and the elimination of an amino group.
