title: 2,6-Di(arylamino)-3-fluoropyridine Derivatives as HIV Non-Nucleoside Reverse Transcriptase Inhibitors.
abstract: New non-nucleoside reverse transcriptase inhibitors (NNRTI), which are similar in structure to earlier described di(arylamino)pyrimidines but featuring a 2,6-di(arylamino)-3-fluoropyridine, 2,4-di(arylamino)-5-fluoropyrimidine, or 1,3-di(arylamino)-4-fluorobenzene moiety instead of a 2,4-disubstituted pyrimidine moiety, are reported. The short and practical synthesis of novel NNRTI relies on two sequential Pd-catalyzed aminations as the key steps. It is demonstrated through direct comparison with reference compounds that the presence of a fluorine atom increases the in vitro anti-HIV activity, both against the wild type virus and drug-resistant mutant strains.
authors.affiliation: Organic Synthesis Division, Department of Chemistry, University of Antwerp , Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Sergey
authors.initials: S
authors.lastname: Sergeyev
authors.affiliation: Organic Synthesis Division, Department of Chemistry, University of Antwerp , Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Yadav
authors.affiliation: Organic Synthesis Division, Department of Chemistry, University of Antwerp , Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Philippe
authors.initials: P
authors.lastname: Franck
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine , Nationalestraat 155, B-2000 Antwerp, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Michiels
authors.affiliation: Shakturana CV , Pater van Mierlostraat 18, 2300 Turnhout, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Lewi
authors.affiliation: Heeres Consulting CV , Leemskuilen 18, 2350 Vosselaar, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Heeres
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine , Nationalestraat 155, B-2000 Antwerp, Belgium.|Department of Biomedical Sciences, University of Antwerp , Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Guido
authors.initials: G
authors.lastname: Vanham
authors.affiliation: Virology Unit, Department of Biomedical Sciences, Institute of Tropical Medicine , Nationalestraat 155, B-2000 Antwerp, Belgium.
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Ariën
authors.affiliation: Faculty of Applied Sciences, University of Antwerp , Salesianenlaan 90, 2660 Hoboken, Belgium.
authors.forename: Christophe M L
authors.initials: CM
authors.lastname: Vande Velde
authors.affiliation: Medicinal Chemistry, Department of Pharmaceutical Sciences, University of Antwerp , Universiteitsplein 1, 2610 Wilrijk, Belgium.
authors.forename: Hans
authors.initials: H
authors.lastname: De Winter
authors.affiliation: Organic Synthesis Division, Department of Chemistry, University of Antwerp , Groenenborgerlaan 171, B-2020 Antwerp, Belgium.
authors.forename: Bert U W
authors.initials: BU
authors.lastname: Maes
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000814:Aniline Compounds; D019380:Anti-HIV Agents; D005464:Fluorobenzenes; D011725:Pyridines; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase