1028256-60-1Relevant articles and documents
Discovery of a novel, selective, and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position
Feng, Dong-Mei,Gardell, Stephen J.,Lewis, S. Dale,Bock, Mark G.,Chen, Zhongguo,Freidinger, Roger M.,Naylor-Olsen, Adel M.,Ramjit, Harri G.,Woltmann, Richard,Baskin, Elizabeth P.,Lynch, Joseph J.,Lucas, Robert,Shafer, Jules A.,Dancheck, Kimberley B.,Chen, I.-Wu,Mao, Shi-Shan,Krueger, Julie A.,Hare, Timothy R.,Mulichak, Anne M.,Vacca, Joseph P.
, p. 3726 - 3733 (2007/10/03)
A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (K(i) 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral P1 was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at P1 was a key step in our search for a clinical candidate.
