2. Academic Validation
  3. In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine)

In search of a novel anti-HIV drug: multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6-dimethylphenyl]amino]-2- pyrimidinyl]amino]benzonitrile (R278474, rilpivirine)

  • J Med Chem. 2005 Mar 24;48(6):1901-9. doi: 10.1021/jm040840e.
Paul A J Janssen 1,  Paul J Lewi,  Eddy Arnold,  Frits Daeyaert,  Marc de Jonge,  Jan Heeres,  Luc Koymans,  Maarten Vinkers,  Jérôme Guillemont,  Elisabeth Pasquier,  Mike Kukla,  Don Ludovici,  Koen Andries,  Marie-Pierre de Béthune,  Rudi Pauwels,  Kalyan Das,  Art D Clark Jr,  Yulia Volovik Frenkel,  Stephen H Hughes,  Bart Medaer,  Fons De Knaep,  Hilde Bohets,  Fred De Clerck,  Ann Lampo,  Peter Williams,  Paul Stoffels
Affiliations

Affiliation

  • 1 Center for Molecular Design, Janssen Pharmaceutica, B-2350 Vosselaar, Belgium.
PMID: 15771434 DOI: 10.1021/jm040840e
Abstract

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.

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