N¹,N³-disubstituted uracils as nonnucleoside inhibitors of HIV-1 reverse transcriptase

详细信息    查看全文

• 作者：Mikhail S. Novikov^a ; Vladimir T. Valuev-Elliston^b ; Denis A. Babkov^a ; Maria P. Paramonova^a ; Alexander V. Ivanov^b ; Sergey A Gavryushov^b ; Anastasia L. Khandazhinskaya^b ; Sergey N. Kochetkov^b ; Christophe Pannecouque^c ; Graciela Andrei^c ; Robert Snoeck^c ; Jan Balzarini^c ; Katherine L. Seley-Radtke^d ; ^{kseley@umbc.edu}
• 关键词：Nonnucleoside reverse transcriptase inhibitors ; NNRTIs ; HIV ; Uracil ; Benzophenone ; Cinnamyl
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 March, 2013
• 年：2013
• 卷：21
• 期：5
• 页码：1150-1158
• 全文大小：570 K

文摘

A series of phenyloxyethyl and cinnamyl derivatives of substituted uracils were synthesized and found to exhibit potent activity against HIV-RT and HIV replication in cell culture. In general, the cinnamyl derivatives proved superior to the phenyloxyethyl derivatives, however 1-[2-(4-methylphenoxy)ethyl]-3-(3,5-dimethylbenzyl)uracil (19) exhibited the highest activity (EC₅₀ = 0.27 ¦ÌM) thus confirming that the 3-benzyluracil fragment in the NNRTI structure can be regarded as a functional analogue of the benzophenone pharmacophore typically found in NNRTIs.