| Literature DB >> 9371237 |
D M Feng1, S J Gardell, S D Lewis, M G Bock, Z Chen, R M Freidinger, A M Naylor-Olsen, H G Ramjit, R Woltmann, E P Baskin, J J Lynch, R Lucas, J A Shafer, K B Dancheck, I W Chen, S S Mao, J A Krueger, T R Hare, A M Mulichak, J P Vacca.
Abstract
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 (Ki 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.Entities:
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Year: 1997 PMID： 9371237 DOI： 10.1021/jm970493r
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446