Scaffold hopping: Exploration of acetanilide-containing uracil analogues as potential NNRTIs. Issue 5 (1st March 2015)

• Record Type: Journal Article
• Authors: Babkov, Denis A.; Valuev-Elliston, Vladimir T.; Paramonova, Maria P.; Ozerov, Alexander A.; Ivanov, Alexander V.; Chizhov, Alexander O.; Khandazhinskaya, Anastasia L.; Kochetkov, Sergey N.; Balzarini, Jan; Daelemans, Dirk; Pannecouque, Christophe; Seley-Radtke, Katherine L.; Novikov, Mikhail S.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 5(2015)
• Page Start: 1069
• Page End: 1081
• Publication Date: 2015-03-01
• Subjects: Nonnucleoside reverse transcriptase -- Inhibitors -- NNRTIs -- HIV -- Uracil -- Amide; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.01.002
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: In order to identify novel nonnucleoside inhibitors of HIV-1 reverse transcriptase two series of amide-containing uracil derivatives were designed as hybrids of two scaffolds of previously reported inhibitors. Subsequent biological evaluation confirmed acetamide uracil derivatives15a –k as selective micromolar NNRTIs with a first generation-like resistance profile. Molecular modeling of the most active compounds15c and15i was employed to provide insight on their inhibitory properties and direct future design efforts.