Abstract
With the worldwide number of human immunodeficiency virus positive patients stagnant and the increasing emergence of viral strains resistant to current treatment, the development of novel anti-human immunodeficiency virus drug candidates is a perpetual quest of medicinal chemists. Herein, we report a novel group of diarylpyrimidines, non-nucleoside reverse transcriptase inhibitors, which represents an important class of current anti-human immunodeficiency virus therapy. Series of diarylpyrimidines containing o, o-difluorophenyl (A-arm), 4-cyanophenylamino (B-arm), and a small substituent (e.g. NH2, OMe) at positions 2, 4, and 6 of the pyrimidine ring were prepared. The A-arm was modified in the para position (F or OMe) and linked to the central pyrimidine core with a variable spacer (CO, O, NH). Antiviral activities of 20 compounds were measured against wild type human immunodeficiency virus-1 and mutant reverse transcriptase strains (K103N, Y181C) using a cytoprotection assay. To the most promising structural motives belong the o, o-difluoro- p-methoxy A-arm in position 4, and the amino group in position 6 of pyrimidine. Single digit nanomolar activities with no significant toxicity (CC50 > 17,000 nM) were found for compounds ...Continue Reading
References
Oct 11, 1996·Journal of Medicinal Chemistry·A S CantrellH Zhang
Oct 1, 1998·Antiviral Research·E De Clercq
Aug 31, 2001·Bioorganic & Medicinal Chemistry Letters·D W LudoviciP A Janssen
Mar 18, 2005·Journal of Medicinal Chemistry·Paul A J JanssenPaul Stoffels
Dec 29, 2006·Chemistry & Biodiversity·Erik De Clercq
Jan 16, 2007·European Journal of Medicinal Chemistry·Céline MordantJerome Guillemont
Jul 10, 2007·Lancet·José Valdez MadrugaUNKNOWN DUET-1 study group
Jul 10, 2007·Lancet·Adriano LazzarinBrian Woodfall
Jun 24, 2008·The Journal of Antimicrobial Chemotherapy·Anna Maria Geretti
Mar 31, 2009·European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Für Pharmazeutische Verfahrenstechnik E.V·Lieven BaertJan Rosier
Sep 8, 2009·Bioorganic & Medicinal Chemistry Letters·Simon T BedfordIan A Yule
Sep 29, 2009·Antiviral Research·Marie-Pierre de Béthune
Mar 24, 2010·Bioorganic & Medicinal Chemistry·Xiao-Qing FengErik De Clercq
Mar 25, 2010·ChemMedChem·Zhao-Sen ZengErik De Clercq
May 5, 2010·Journal of Medicinal Chemistry·Eric B LansdonXiaohong Liu
Jun 12, 2010·Bioorganic & Medicinal Chemistry Letters·Denis J KerteszKlaus Klumpp
Mar 29, 2011·Journal of Medicinal Chemistry·Dante RotiliAntonello Mai
Apr 28, 2011·Medicinal Research Reviews·Peng ZhanXinyong Liu
Aug 10, 2011·Bioorganic & Medicinal Chemistry·Shuang-Xi GuChristophe Pannecouque
Oct 13, 2011·ChemMedChem·Xiao-Dong MaChristophe Pannecouque
Jan 25, 2012·Journal of Medicinal Chemistry·Dongyue LiXinyong Liu
Jan 1, 2011·Chemical Science·David S Surry, Stephen L Buchwald
May 24, 2012·Chemical Society Reviews·Chevonne ReynoldsMoira L Bode
Nov 19, 2013·Bioorganic & Medicinal Chemistry Letters·Xuwang ChenXinyong Liu
Apr 1, 2014·Bioorganic & Medicinal Chemistry·Zi-Hong YanChristophe Pannecouque
May 6, 2014·Bioorganic & Medicinal Chemistry·Zi-Hong YanChristophe Pannecouque
Jun 22, 2014·European Journal of Medicinal Chemistry·Ge MengJan Balzarini
Jun 24, 2014·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Yang LiuJan Balzarini
Sep 20, 2015·Bioorganic & Medicinal Chemistry·Shuang-Xi GuChristophe Pannecouque
Oct 29, 2015·Journal of Medicinal Chemistry·Peng ZhanXinyong Liu
Jun 29, 2016·Public Health·J PoorolajalE Jenabi
Jul 3, 2016·European Journal of Medicinal Chemistry·Petr ŠimonZlatko Janeba