177583-50-5Relevant academic research and scientific papers
Potent noncovalent thrombin inhibitors that utilize the unique amino acid D-dicyclohexylalanine in the P3 position. Implications on oral bioavailability and antithrombotic efficacy
Tucker, Thomas J.,Lumma, William C.,Lewis, S. Dale,Gardell, Stephen J.,Lucas, Bobby J.,Baskin, Elizabeth P.,Woltmann, Richard,Lynch, Joseph J.,Lyle, Elizabeth A.,Appleby, Sandra D.,Chen, I.-Wu,Dancheck, Kimberley B.,Vacca, Joseph P.
, p. 1565 - 1569 (2007/10/03)
In an effort to prepare orally bioavailable analogs of our previously reported thrombin inhibitor 1, we have synthesized a series of compounds that utilize the unique amino acid D-dicyclohexylalanine as a P3 ligand. The resulting compounds are extremely p
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.
