title: Design, synthesis, and biological evaluation of novel 5-Alkyl-6-Adamantylmethylpyrimidin-4(3H)-ones as HIV-1 non-nucleoside reverse-transcriptase inhibitors.
abstract: A series of novel 5-alkyl-6-Adamantylmethylpyrimidin-4(3H)-ones bearing various substituents at the C-2 position of the pyrimidinone ring were synthesized using a facile route and evaluated for their anti-HIV activity in MT-4 cells. The biological results demonstrated that the majority of the newly designed compounds possessed moderate efficiency in inhibiting the replication of the wild-type (WT) HIV-1 strain (IIIB ) with EC50 values in the range from 0.10 to 5.39 μm. Among them, 5b1 and 5b3 proved to be the two most active inhibitors against WT HIV-1 with EC50 values of 0.10 and 0.12 μm, respectively, which were more active than nevirapine (NVP) in the same assay. In addition, HIV-1 reverse-transcriptase (RT) inhibition assay indicated that the representative compound 5b1 showed affinity to WT HIV-1 RT, and inhibited the activity of RT with an IC50 value superior to the reference drug NVP. Moreover, the preliminary structure-activity relationship (SAR) and the molecular modeling analysis of these new derivatives are also discussed.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
authors.forename: Wenxin
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
authors.forename: Boshi
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Kang
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Dirk
authors.initials: D
authors.lastname: Daelemans
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhan
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Ji'nan, Shandong, China.
authors.forename: Xinyong
authors.initials: X
authors.lastname: Liu
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D011743:Pyrimidines / Q000737:chemistry / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D019380:Anti-HIV Agents; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors
keywords: HIV-1; NNRTIs; S-DABOs; anti-HIV-1 activity; drug design