| Autor: |
Feng DM; Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486, USA., Gardell SJ, Lewis SD, Bock MG, Chen Z, Freidinger RM, Naylor-Olsen AM, Ramjit HG, Woltmann R, Baskin EP, Lynch JJ, Lucas R, Shafer JA, Dancheck KB, Chen IW, Mao SS, Krueger JA, Hare TR, Mulichak AM, Vacca JP |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1997 Nov 07; Vol. 40 (23), pp. 3726-33. |
| DOI: |
10.1021/jm970493r |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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