Design, synthesis, and biological evaluation of novel 5-Alkyl-6-Adamantylmethylpyrimidin-4(3H)-ones as HIV-1 non-nucleoside reverse-transcriptase inhibitors

作者：Li, Wenxin; Huang, Boshi; Kang, Dongwei; De Clercq, Erik; Daelemans, Dirk; Pannecouque, Christophe; Zhan, Peng^*; Liu, Xinyong^*

来源：Chemical Biology & Drug Design, 2016, 88(3): 380-385.

DOI：10.1111/cbdd.12765

• anti-HIV-1 activity
• drug design
• HIV-1
• NNRTIs
• S-DABOs

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 5.39m. Among them, 5b1 and 5b3 proved to be the two most active inhibitors against WT HIV-1 with EC50 values of 0.10 and 0.12m, 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.

• 出版日期2016-9
• 单位河北医科大学; 山东大学