title: Synthesis and biological evaluation of novel 6-substituted 5-alkyl-2-(arylcarbonylmethylthio)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
abstract: A novel series of 2-arylcarbonylmethylthio-6-arylmethylpyrimidin-4(3H)-ones have been synthesized and evaluated for in vitro anti-HIV activities in MT-4 cells. Most of these new compounds showed moderate to potent activities against wild-type HIV-1 with an EC(50) range from 8.97 microM to 0.010 microM. Among them, the 6-(3,5-dimethylbenzyl) analogue 5p was identified as the most promising compound (EC(50)=0.010 microM, SI>31,800) associated with moderate activity against the HIV-1 double mutant RT strain K103N+Y181C. The structure-activity relationships of these new congeners were further discussed.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
authors.forename: Yue-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Fen-Er
authors.initials: FE
authors.lastname: Chen
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
mesh_terms: D000478:Alkylation; D002460:Cell Line; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000737:chemistry*
chemical_list: D009705:Nucleosides; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013438:Sulfhydryl Compounds