| Literature DB >> 9871547 |
P E Sanderson1, K J Cutrona, B D Dorsey, D L Dyer, C M McDonough, A M Naylor-Olsen, I W Chen, Z Chen, J J Cook, S J Gardell, J A Krueger, S D Lewis, J H Lin, B J Lucas, E A Lyle, J J Lynch, M T Stranieri, K Vastag, J A Shafer, J P Vacca.
Abstract
Replacement of the amidinopiperidine P1 group of 3-benzylsulfonylamino-6-methyl-2-pyridinone acetamide thrombin inhibitor L-373,890 (2) with a mildly basic 5-linked 2-amino-6-methylpyridine results in an equipotent compound L-374,087 (5, Ki = 0.5 nM). Compound 5 is highly selective for thrombin over trypsin, is efficacious in the rat ferric chloride model of arterial thrombosis and is orally bioavailable in dogs and cynomolgus monkeys. The structural basis for the critical importance of both methyl groups in 5 was confirmed by X-ray crystallography.Entities:
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Year: 1998 PMID： 9871547 DOI： 10.1016/s0960-894x(98)00117-6
Source DB: PubMed Journal: Bioorg Med Chem Lett ISSN： 0960-894X Impact factor: 2.823