title: Scaffold hopping: exploration of acetanilide-containing uracil analogues as potential NNRTIs.
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 derivatives 15a-k as selective micromolar NNRTIs with a first generation-like resistance profile. Molecular modeling of the most active compounds 15c and 15i was employed to provide insight on their inhibitory properties and direct future design efforts.
authors: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia.
authors: Denis A
authors: DA
authors: Babkov
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str., 32, Moscow 119991, Russia.
authors: Vladimir T
authors: VT
authors: Valuev-Elliston
authors: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia.
authors: Maria P
authors: MP
authors: Paramonova
authors: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia.
authors: Alexander A
authors: AA
authors: Ozerov
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str., 32, Moscow 119991, Russia.
authors: Alexander V
authors: AV
authors: Ivanov
authors: Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Leninsky pr., 47, Moscow 119991, Russia.
authors: Alexander O
authors: AO
authors: Chizhov
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str., 32, Moscow 119991, Russia.
authors: Anastasia L
authors: AL
authors: Khandazhinskaya
authors: Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str., 32, Moscow 119991, Russia.
authors: Sergey N
authors: SN
authors: Kochetkov
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium.
authors: Jan
authors: J
authors: Balzarini
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium.
authors: Dirk
authors: D
authors: Daelemans
authors: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium.
authors: Christophe
authors: C
authors: Pannecouque
authors: Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
authors: Katherine L
authors: KL
authors: Seley-Radtke
authors: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia.
authors: Mikhail S
authors: MS
authors: Novikov
mesh_terms: D000083:Acetanilides / Q000737:chemistry*; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D006801:Humans; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D014498:Uracil / Q000031:analogs & derivatives*
chemical_list: D000083:Acetanilides; D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D014498:Uracil; C508827:acetanilide
keywords: Amide; HIV; Inhibitors; NNRTIs; Nonnucleoside reverse transcriptase; Uracil