1,6-Bis[(benzyloxy)methyl]uracil derivatives—Novel antivirals with activity against HIV-1 and influenza H1N1 virus

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• 作者：Alexander N. Geisman^a ; Vladimir T. Valuev-Elliston^b ; Alexander A. Ozerov^a ; Anastasia L. Khandazhinskaya^b ; Alexander O. Chizhov^c ; Sergey N. Kochetkov^b ; Christophe Pannecouque^d ; Lieve Naesens^d ; Katherine L. Seley-Radtke^e ; ^{kseley@umbc.edu" class="auth_mail" title="E-mail the corresponding author} ; Mikhail S. Novikov^a
• 关键词：Uracil ; Non-nucleoside reverse transcriptase inhibitors ; NNRTIs ; HIV ; Influenza virus
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2016
• 出版时间：1 June 2016
• 年：2016
• 卷：24
• 期：11
• 页码：2476-2485
• 全文大小：1205 K

文摘

A series of 1,6-bis[(benzyloxy)methyl]uracil derivatives combining structural features of both diphenyl ether and pyridone types of NNRTIs were synthesized. Target compounds were found to inhibit HIV-1 reverse transcriptase at micro- and submicromolar levels of concentrations and exhibited anti-HIV-1 activity in MT-4 cell culture, demonstrating resistance profile similar to first generation NNRTIs. The synthesized compounds also showed profound activity against influenza virus (H1N1) in MDCK cell culture without detectable cytotoxicity. The lead compound of this assay appeared to exceed rimantadine, amantadine, ribavirin and oseltamivir carboxylate in activity. The mechanism of action of 1,6-bis[(benzyloxy)methyl]uracils against influenza virus is currently under investigation.