title: Synthesis of novel diarylpyrimidine analogues of TMC278 and their antiviral activity against HIV-1 wild-type and mutant strains.
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.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, Medicinal Chemistry Department, Campus de Maigremont BP315, F-27106 Val de Reuil Cedex, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Mordant
authors.forename: Benoit
authors.initials: B
authors.lastname: Schmitt
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Pasquier
authors.forename: Christophe
authors.initials: C
authors.lastname: Demestre
authors.forename: Laurence
authors.initials: L
authors.lastname: Queguiner
authors.forename: Chantal
authors.initials: C
authors.lastname: Masungi
authors.forename: Anik
authors.initials: A
authors.lastname: Peeters
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Smeulders
authors.forename: Eva
authors.initials: E
authors.lastname: Bettens
authors.forename: Kurt
authors.initials: K
authors.lastname: Hertogs
authors.forename: Jan
authors.initials: J
authors.lastname: Heeres
authors.forename: Paul
authors.initials: P
authors.lastname: Lewi
authors.forename: Jerome
authors.initials: J
authors.lastname: Guillemont
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D005260:Female; D015497:HIV-1 / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D000068696:Rilpivirine; D013056:Spectrophotometry, Ultraviolet
chemical_list: D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D000068696:Rilpivirine