Portal de Periódicos da CAPES

In Search of a Novel Anti-HIV Drug: Multidisciplinary Coordination in the Discovery of 4-[[4-[[4-[(1 E )-2-Cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, Rilpivirine)

2004; American Chemical Society; Volume: 48; Issue: 6 Linguagem: Inglês

10.1021/jm040840e

1520-4804

Paul A. J. Janssen, Paul Lewi, Eddy Arnold, Frits Daeyaert, Marc R. de Jonge, Jan Heeres, Luc Koymans, Maarten Vinkers, Jérôme Guillemont, Élisabeth Pasquier, Mike Kukla, D.W. Ludovici, Koen Andries, Marie‐Pierre de Béthune, Rudi Pauwels, Kalyan Das, Art D. Clark, Yulia Volovik Frenkel, Stephen H. Hughes, Bart Medaer, Fons De Knaep, Hilde Bohets, Fred De Clerck, Ann Lampo, Peter Williams, Paul Stoffels,

Biochemical and Molecular Research

Ideally, an anti-HIV drug should (1) be highly active against wild-type and mutant HIV without allowing breakthrough; (2) have high oral bioavailability and long elimination half-life, allowing once-daily oral treatment at low doses; (3) have minimal adverse effects; and (4) be easy to synthesize and formulate. R278474, a new diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI), appears to meet these criteria and to be suitable for high compliance oral treatment of HIV-1 infection. The discovery of R278474 was the result of a coordinated multidisciplinary effort involving medicinal chemists, virologists, crystallographers, molecular modelers, toxicologists, analytical chemists, pharmacists, and many others.