Diaryl ethers with carboxymethoxyphenacyl motif as potent HIV-1 reverse transcriptase inhibitors with improved solubility

Journal of Enzyme Inhibition and Medicinal Chemistry

Bruno Verhasselt¹  Evelien Naessens¹  Piotr Paneth²  Tomasz Frączek²  Rafał Kamiński²  Agnieszka Krakowiak³ 

[1] Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent University Hospital, Ghent, Belgiu;Institute of Applied Radiation Chemistry, Lodz University of Technology, Lodz, Poland;Institute of Applied Radiation Chemistry, Lodz University of Technology, Lodz, Poland;Department of Bioorganic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Lodz, Poland;

关键词: NNRTI;    reverse transcriptase;    HIV;    drug solubility;   

DOI  :  10.1080/14756366.2017.1387542

来源: publisher

【 摘 要 】

In search of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) with improved solubility, two series of novel diaryl ethers with phenacyl moiety were designed and evaluated for their HIV-1 reverse transcriptase inhibition potentials. All compounds exhibited good to excellent results with IC50 at low micromolar to submicromolar concentrations. Two most active compounds (7e and 7 g) exhibit inhibitory potency comparable or even better than that of nevirapine and rilpivirine. Furthermore, SupT1 and CD4+ cell infectivity assays for the most promising (7e) have confirmed its strong antiviral potential while docking studies indicate a novel binding interactions responsible for high activity.

【 授权许可】

CC BY