title: 1-[2-(2-Benzoyl- and 2-benzylphenoxy)ethyl]uracils as potent anti-HIV-1 agents.
abstract: Non-nucleoside reverse transcriptase inhibitors (NNRTI) are key components in highly active antiretroviral therapy for treating HIV-1. Herein we present the synthesis for a series of N1-alkylated uracil derivatives bearing ω-(2-benzyl- and 2-benzoylphenoxy)alkyl substituents as novel NNRTIs. These compounds displayed anti-HIV activity similar to that of nevirapine and several of them exhibited activity against the K103N/Y181C RT mutant HIV-1 strain. Further evaluation revealed that the inhibitors were active against most nevirapine-resistant mono- and di-substituted RTs with the exception of the V106A RT. Thus, the candidate compounds can be regarded as potential lead compounds against the wild-type virus and drug-resistant forms.
authors: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Paversushikh Bortsov Sq., 1, Volgograd 400131, Russia.
authors: Mikhail S
authors: MS
authors: Novikov
authors: Olga N
authors: ON
authors: Ivanova
authors: Alexander V
authors: AV
authors: Ivanov
authors: Alexander A
authors: AA
authors: Ozerov
authors: Vladimir T
authors: VT
authors: Valuev-Elliston
authors: Kartik
authors: K
authors: Temburnikar
authors: Galina V
authors: GV
authors: Gurskaya
authors: Sergey N
authors: SN
authors: Kochetkov
authors: Christophe
authors: C
authors: Pannecouque
authors: Jan
authors: J
authors: Balzarini
authors: Katherine L
authors: KL
authors: Seley-Radtke
mesh_terms: D019943:Amino Acid Substitution; D001577:Benzophenones / Q000737:chemistry; D002460:Cell Line; D024882:Drug Resistance, Viral / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014498:Uracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D001577:Benzophenones; D018894:Reverse Transcriptase Inhibitors; D014498:Uracil; C047723:benzophenone; D054303:HIV Reverse Transcriptase