title: Synthesis and structure-activity relationship of novel diarylpyrimidines with hydromethyl linker (CH(OH)-DAPYs) as HIV-1 NNRTIs.
abstract: A series of 26 diarylpyrimidines, characterized by the hydroxymethyl linker between the left wing benzene ring and the central pyrimidine, were synthesized and evaluated for in vitro anti-HIV activity. Most of the compounds exhibited moderate to excellent activities against wild-type HIV-1. Among them, compound 10i, bearing a chlorine atom at the C-2 position of left benzene ring, was the best congener and showed potent activity against wild-type HIV-1 with an EC(50) value of 0.009 μM, along with moderate activities against the double RT mutant (K103N+Y181C) HIV-1(III(B)) and HIV-2(ROD) with an EC(50) value of 6.2 and 6.0 μM, respectively. The preliminary structure-activity relationship (SAR) of this new series of compounds was also investigated.
authors.affiliation: Department of Chemistry, Fudan University, Shanghai, People's Republic of China.
authors.forename: Shuang-Xi
authors.initials: SX
authors.lastname: Gu
authors.forename: Qiu-Qin
authors.initials: QQ
authors.lastname: He
authors.forename: Shi-Qiong
authors.initials: SQ
authors.lastname: Yang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Ma
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: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D002460:Cell Line; D002713:Chlorine / Q000737:chemistry; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D009154:Mutation; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: C568682:4-((4-((2-chlorophenyl)(hydroxy)methyl)pyrimidin-2-yl)amino)benzonitrile; D000814:Aniline Compounds; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D002713:Chlorine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase