Heterocyclic core analogs of a direct thrombin inhibitor

…, B Patil, N Chidurala, V Komanduri, S Debnath…

Index: Blizzard, Timothy A.; Singh, Sanjay; Patil, Basanagoud; Chidurala, Naresh; Komanduri, Venukrishnan; Debnath, Samarpita; Belyakov, Sergei; Crespo, Alejandro; Struck, Alice; Kurtz, Marc; Wiltsie, Judyann; Shen, Xun; Sonatore, Lisa; Arocho, Marta; Lewis, Dale; Ogletree, Martin; Biftu, Tesfaye Bioorganic and Medicinal Chemistry Letters, 2014 , vol. 24, # 4 p. 1111 - 1115

Full Text: HTML

Citation Number: 3

Abstract

Abstract Thrombin is a serine protease that plays a key role in blood clotting. Pyrrolidine 1 is a potent thrombin inhibitor discovered at Merck several years ago. Seven analogs (2–8) of 1 in which the pyrrolidine core was replaced with various heterocycles were prepared and evaluated for activity against thrombin, clotting factors VIIa, IXa, Xa, and XIIa, and trypsin. The thiomorpholine analog 6 was the most active, essentially matching the thrombin ...