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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)

Janssen, Paul A. J., Lewi, Paul J., Arnold, Eddy, Daeyaert, Frits, de Jonge, Marc, Heeres, Jan, Koymans, Luc, Vinkers, Maarten, Guillemont, Jérôme, Pasquier, Elisabeth, Kukla, Mike, Ludovici, Don, Andries, Koen, de Béthune, Marie-Pierre, Pauwels, Rudi, Das, Kalyan, Clark,, Art D., Frenkel, Yulia Volovik, Hughes, Stephen H., Medaer, Bart, De Knaep, Fons, Bohets, Hilde, De Clerck, Fred, Lampo, Ann, Williams, Peter, Stoffels, Paul·2005·Journal of Medicinal Chemistry

DOI 10.1021/jm040840e

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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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Authors: Janssen, P. A. J., Lewi, P. J., Arnold, E., Daeyaert, F., de Jonge, M., Heeres, J., Koymans, L., Vinkers, M., Guillemont, J., Pasquier, E., Kukla, M., Ludovici, D., Andries, K., de Béthune, M.-P., Pauwels, R., Das, K., Clark, Frenkel, Y. V., Hughes, S. H., Medaer, B., De Knaep, F., Bohets, H., De Clerck, F., Lampo, A., Williams, P., & Stoffels, P.
Venue: Journal of Medicinal Chemistry
Publisher: American Chemical Society (ACS)
Published: 2004-11-06
Volume: 48
Issue: 6
Pages: 1901-1909
ISSN: 0022-2623 (ISSN-L)
1520-4804
DOI: 10.1021/jm040840e
OpenAlex: W2109893413
Cited by: 347
References: 46
FWCI: 7.84
Type: journal article
Language: en
Open access: closed

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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)

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