Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains

  • Eur J Med Chem. 2007 May;42(5):567-79. doi: 10.1016/j.ejmech.2006.11.014.
Céline Mordant  1 ,  Benoit Schmitt ,  Elisabeth Pasquier ,  Christophe Demestre ,  Laurence Queguiner ,  Chantal Masungi ,  Anik Peeters ,  Liesbeth Smeulders ,  Eva Bettens ,  Kurt Hertogs ,  Jan Heeres ,  Paul Lewi ,  Jerome Guillemont
Affiliations
  • 1. Johnson & Johnson Pharmaceutical Research and Development, Medicinal Chemistry Department, Campus de Maigremont BP315, F-27106 Val de Reuil Cedex, France.
PMID: 17223230 DOI: 10.1016/j.ejmech.2006.11.014
Abstract

Novel diarylpyrimidines (DAPY), which represent next generation of non-nucleoside Reverse Transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus type I (HIV-1) assessed. Modulations at positions 2 and 6 of the left phenyl ring generated interesting derivatives of TMC278 displaying high potency against wild-type and mutant viruses compared to nevirapine and efavirenz. The pharmacokinetic profile of the best newly synthesized DAPY was evaluated and compared with TMC278 now in phase II clinical trials.