- A stereo configuration-activity study of 3-iodo-4-(2-methylcyclohexyloxy)-6-phenethylpyridin-2(2H)-ones as potency inhibitors of HIV-1 variants
-
3-Iodo-4-(2′-methylcyclohexyloxy)-6-phenethylpyridin-2(1H)-ones, as effective non-nucleoside reverse transcriptase inhibitors, were synthesized and resolved with different configurations. Biological results revealed that the trans-racemate 2b exhibited more potent activity than the cis-isomers. Noticeably, the trans-(S,S)-enantiomer 2e turned out to be significantly more potent than its counterpart enantiomer 2d against wild-type and double-mutant strains with high selectivity indexes.
- Wu, Shaotong,Yin, Qianqian,Zhao, Liang,Fan, Ningning,Tang, Xiaowan,Zhao, Jianxiong,Sheng, Tao,Guo, Ying,Tian, Chao,Zhang, Zhili,Xu, Weisi,Liu, Zhenming,Jiang, Shibo,Ma, Liying,Liu, Junyi,Wang, Xiaowei
-
p. 1413 - 1420
(2016/02/03)
-
- Novel pyridinone derivatives as non-nucleoside reverse transcriptase inhibitors (NNRTIs) with high potency against NNRTI-resistant HIV-1 strains
-
Novel 6-substituted-4-cycloalkyloxy-pyridin-2(1H)-ones were synthesized as non-nucleoside reverse transcriptase inhibitors (NNRTIs), and their biological activity was evaluated. Most of the compounds, especially 26 and 22, bearing a 3-isopropyl and 3-iodine group, respectively, exhibited highly potent activity against wild-type HIV-1 strains and those resistant to reverse transcriptase inhibitors (RTIs). The diastereoisomers of 26-trans and 26-cis were synthesized separately and confirmed with HPLC and NOESY spectra. The 26-trans isomers had an activity about 400-fold more potent than that of 26-cis. The pair of 26-trans enantiomers, one of the most potent inhibitors with EC50 of 4 nM and selectivity index (SI) of 75000, was highly effective against a panel of RTIs-resistant strains with single (Y181C and K103N) or double (A17) mutations in reverse transcriptase. The results suggest that these novel pyridinone derivatives have the potential to be further developed as new antiretroviral drugs with improved antiviral efficacy and drug resistance profile.
- Li, Amin,Ouyang, Yabo,Wang, Ziyun,Cao, Yuanyuan,Liu, Xiangyi,Ran, Li,Li, Chao,Li, Li,Zhang, Liang,Qiao, Kang,Xu, Weisi,Huang, Yang,Zhang, Zhili,Tian, Chao,Liu, Zhenming,Jiang, Shibo,Shao, Yiming,Du, Yansheng,Ma, Liying,Wang, Xiaowei,Liu, Junyi
-
p. 3593 - 3608
(2013/06/27)
-