title: Synthesis and biological evaluation of novel 2-(substituted phenylaminocarbonylmethylthio)-6-(2,6-dichlorobenzyl)-pyrimidin-4(3H)-ones as potent HIV-1 NNRTIs.
abstract: A series of novel 2-(phenylaminocarbonylmethylthio)-6-(2,6-dichlorobenzyl)-pyrimidin-4(3H)-ones have been designed and synthesized. All of the new compounds were evaluated for their 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) ranging from 4.48microM to 0.18microM. Among them, 2-[(4-bromophenylamino)carbonylmethylthio]-6-(2,6-dichlorobenzyl)-5-methylpyrimidin-4(3H)-one 4b3 was identified as the most promising compound (EC(50) = 0.18+/-0.06microM, CC(50) >243.56microM, SI >1326). The structure-activity relationship (SAR) of these new congeners is discussed.
authors.affiliation: Institute of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, PR China.
authors.forename: Mingyan
authors.initials: M
authors.lastname: Yu
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Li
authors.forename: Shuai
authors.initials: S
authors.lastname: Liu
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Erik De
authors.initials: ED
authors.lastname: Clercq
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D006801:Humans; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D018894:Reverse Transcriptase Inhibitors