75270-17-6Relevant academic research and scientific papers
Synthesis and Biological Evaluation of Benzophenone Derivatives as Potential HIV-1 Inhibitors
Song, Zhendong,Wang, Ping,Huang, Shanshan,Wang, Changyuan,Wang, Rui-Rui,Yang, Liu-Meng,Zhen, Yuhong,Liu, Kexin,Zheng, Yong-Tang,Ma, Xiaodong
, p. 398 - 405 (2017/06/23)
Background: Although a number of agents can achieve high response in acquired immunodeficiency syndrome (AIDS) patients, safer and more active HIV inhibitors are still needed for the growing number of patients infected with resistant HIV virus strains. GW678248 is one of the most potent benzophenone derivatives, exhibiting high potency against a panel of HIV-1 virus (wild-type, K103N mutant, Y181C, etc.) at 1 nmol/L concentrations. However, the safety issues associated with rash and liver metabolic enzymes ultimately led to discontinue its further deve-lopment. As a continuation of our structural modifications on this template, in this manuscript, a new series of benzophenones are described as potential HIV inhibitors. Methods: All the title molecules were synthesized according to the routes in Scheme 1 and Scheme 2, and were tested for anti-HIV-1 activity using the MTT method. In the molecular simulation, the docking program of AutoDock 4.0.1 in parallel with the default parameters were used. Results: A series of novel benzophenone derivatives (BPs) with nanomolar anti-HIV-1 activity were identified. Of these inhibitors, analogue 10i (EC50 = 2.9 nmol/L), the most active inhibitor, was comparable to the lead compound GW678248 in inhibiting the wild-type HIV-1 virus. Additionally, analogue 13b, which not only exhibited strong inhibitory activity against the HIV-1 virus (EC50 = 4.2 nmol/L), but also has very low cytotoxicity with a TI value of more than 219178.1 was also discovered. Conclusion: This study led to the identification of a series of benzophenone derivatives with nanomolar level of anti-HIV-1 activity. Analogues 10i and 13b, with low cytotoxicity along with high activity are worthy of further development.
Benzophenone Derivatives: A Novel Series of Potent and Selective Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase
Wyatt, Paul G.,Bethell, Richard C.,Cammack, Nicholas,Charon, Daniel,Dodic, Nerina,et al.
, p. 1657 - 1665 (2007/10/02)
A series of benzophenone derivatives has been synthesized and evaluated as inhibitors of HIV-1 reverse transcriptase (RT) and the growth of HIV-1 in MT-4 cells.Through the use of the structure-activity relationships within this series of compounds and computational chemistry techniques, a binding conformation is proposed.The SAR also indicated that the major interactions of 1h with the RT enzyme are through hydrogen bonding of the amide and benzophenone carbonyls and ?-orbital interactions with the benzophenone nucleus and an aromatic function separated from the benzophenone by a suitable spacer group.The crystal structure of compound 1h has been determined.A number of compounds with potent inhibitory activity against HIV-1 RT and HIV in cellular assays at levels comparable with AZT and our efforts to identify a metabolically stable analogue are described.
