155511-82-3Relevant articles and documents
Synthesis and biological activity of 5-aryl-4-(4-(5-methyl-1H-imidazol-4-yl)piperidin-1-yl)pyrimidine analogs as potent, highly selective, and orally bioavailable NHE-1 inhibitors
Atwal, Karnail S.,O'Neil, Steven V.,Ahmad, Saleem,Doweyko, Lidia,Kirby, Mark,Dorso, Charles R.,Chandrasena, Gamini,Chen, Bang-Chi,Zhao, Rulin,Zahler, Robert
, p. 4796 - 4799 (2007/10/03)
A series of potent inhibitors of the sodium hydrogen exchanger-1 (NHE-1) is described. Structure-activity relationships identified the 3-methyl-4-fluoro analog 9t as a highly potent (IC50 = 0.0065 μM) and selective (NHE-2/NHE-1 = 1400) non-acylguanidine NHE-1 inhibitor. Pharmacokinetic studies showed that compound 9t has an oral bioavailability of 52% and a plasma half life of 1.5 h in rats. Because of its promising potency, selectivity, and a good pharmacokinetic profile, compound 9t was selected for further studies.