| Literature DB >> 9397180 |
S W Kaldor1, V J Kalish, J F Davies, B V Shetty, J E Fritz, K Appelt, J A Burgess, K M Campanale, N Y Chirgadze, D K Clawson, B A Dressman, S D Hatch, D A Khalil, M B Kosa, P P Lubbehusen, M A Muesing, A K Patick, S H Reich, K S Su, J H Tatlock.
Abstract
Using a combination of iterative structure-based design and an analysis of oral pharmacokinetics and antiviral activity, AG1343 (Viracept, nelfinavir mesylate), a nonpeptidic inhibitor of HIV-1 protease, was identified. AG1343 is a potent enzyme inhibitor (Ki = 2 nM) and antiviral agent (HIV-1 ED50 = 14 nM). An X-ray cocrystal structure of the enzyme-AG1343 complex reveals how the novel thiophenyl ether and phenol-amide substituents of the inhibitor interact with the S1 and S2 subsites of HIV-1 protease, respectively. In vivo studies indicate that AG1343 is well absorbed orally in a variety of species and possesses favorable pharmacokinetic properties in humans. AG1343 (Viracept) has recently been approved for marketing for the treatment of AIDS.Entities:
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Year: 1997 PMID： 9397180 DOI： 10.1021/jm9704098
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446