Synthesis and biological evaluation of pyridinone analogues as novel potent HIV-1 NNRTIs. Issue 1 (1st January 2015)

• Record Type: Journal Article
• Authors: Cao, Yuanyuan; Zhang, Yu; Wu, Shaotong; Yang, Quanzhi; Sun, Xuefeng; Zhao, Jianxiong; Pei, Fen; Guo, Ying; Tian, Chao; Zhang, Zhili; Wang, Haining; Ma, Liying; Liu, Junyi; Wang, Xiaowei
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 1(2015)
• Page Start: 149
• Page End: 159
• Publication Date: 2015-01-01
• Subjects: HIV human immunodeficiency virus -- NNRTIs non-nucleoside reverse transcriptase inhibitors -- SARs structure and activity relationships -- HAART highly active antiretroviral therapy -- RT reverse transcriptase -- NVP nevirapine -- DLV delavirdine -- EFV efavirenz -- ETR etravirine -- RPV rilpivirine -- RTIs reverse transcriptase inhibitors -- NIS N-iodosuccinimide -- NBS N-bromosuccinimide -- DMF N, N-dimethylformamide -- NNBP non-nucleoside binding pocket -- PDB protein database -- SI selectivity index; Pyridinone analogues -- HIV-1 -- NNRTIs; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2014.11.012
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: A novel 2-pyridinone scaffold was rationally designed and synthesized based on the active anti-HIV agent 1 (LAM- trans ) via an efficient method. The biological results revealed that some target compounds inhibited HIV-1 reverse transcriptase in the lower micromolar concentration range (IC50 0.089–0.68 μm). Notably, the most promising compound 25b exhibited extremely potent inhibitory activity against HIV-1 replication with an EC50 value of 0.0563 μM and the viral selectivity index amounted to 3466.8. Molecular modeling studies were performed, and some SARs were rationalized.