1379464-91-1Relevant academic research and scientific papers
Synthesis, biological evaluation and molecular docking study of N-(2-methoxyphenyl)-6-((4-nitrophenyl)sulfonyl)benzamide derivatives as potent HIV-1 Vif antagonists
Zhou, Meng,Luo, Rong-Hua,Hou, Xue-Yan,Wang, Rui-Rui,Yan, Guo-Yi,Chen, Huan,Zhang, Rong-Hong,Shi, Jian-You,Zheng, Yong-Tang,Li, Rui,Wei, Yu-Quan
, p. 310 - 324 (2017)
Viral infectivity factor (Vif) is protective against APOBEC3G (A3G)-mediated viral cDNA hypermutations, and development of molecules that inhibit Vif mediated A3G degradation is a novel strategy for blocking HIV-1 replication. Through optimizations of the central ring of N-(2-methoxyphenyl)-2-((4-nitrophenyl)thio)benzamide (RN-18), we found a potent compound 12c with EC50value of 1.54?μM, enhancing the antiviral activity more than 150-fold compared with RN-18 in nonpermissive H9 cells. 12c protected A3G from degradation by inhibiting Vif function. Besides, 12c suppressed different HIV-1 clinical strains (HIV-1KM018, HIV-1TC-1and HIV-1WAN) and drug-resistant strains (NRTI, NNRTI, PI, and FI) with relatively high activities. Amidation of 12c with glycine gave a prodrug 13a, improving the water solubility about 2600-fold compared with 12c. Moreover, 13a inhibited the virus replication efficiently with an EC50value of 0.228?μM. These results suggested that the prodrug 13a is a promising candidate agent for the treatment of AIDS.
SAR and lead optimization of an HIV-1 Vif-APOBEC3G axis inhibitor
Mohammed, Idrees,Parai, Maloy K.,Jiang, Xinpeng,Sharova, Natalia,Singh, Gatikrushna,Stevenson, Mario,Rana, Tariq M.
, p. 465 - 469 (2012/09/22)
We describe structure-activity relationship and optimization studies of RN-18, an HIV-1 Vif-APOBEC3G axis inhibitor. Targeted modifications of RN-18 ring C, ring B, ring A, bridge A-B, and bridge B-C were performed to identify the crucial structural features, which generated new inhibitors with similar (4g and 4i) and improved (5, 8b, and 11) activities. Two potent water-soluble RN-18 analogues, 17 and 19, are also disclosed, and we describe the results of pharmacological studies with compound 19. The findings described here will be useful in the development of more potent Vif inhibitors and in the design of probes to identify the target protein of RN-18 and its analogues.
