title: Toward the discovery of dual HCMV-VZV inhibitors: Synthesis, structure activity relationship analysis, and cytotoxicity studies of long chained 2-uracil-3-yl-N-(4-phenoxyphenyl)acetamides.
abstract: The need for novel therapeutic options to fight herpesvirus infections still persists. Herein we report the design, synthesis and antiviral evaluation of a new family of non-nucleoside antivirals, derived from 1-[ω-(4-bromophenoxy)alkyl]uracil derivatives--previously reported inhibitors of human cytomegalovirus (HCMV). Introduction of the N-(4-phenoxyphenyl)acetamide side chain at N(3) increased their potency and widened activity spectrum. The most active compounds in the series exhibit submicromolar activity against different viral strains of HCMV and varicella zoster virus (VZV) replication in HEL cell cultures. Inactivity against other DNA and RNA viruses, including herpes simplex virus 1/2, points to a novel mechanism of antiviral action.
authors.affiliation: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia.
authors.forename: Denis A
authors.initials: DA
authors.lastname: Babkov
authors.affiliation: Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilova 32, Moscow 119991, Russia.
authors.forename: Anastasia L
authors.initials: AL
authors.lastname: Khandazhinskaya
authors.affiliation: Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Leninsky pr., 47, Moscow 119991, Russia.
authors.forename: Alexander O
authors.initials: AO
authors.lastname: Chizhov
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium.
authors.forename: Graciela
authors.initials: G
authors.lastname: Andrei
authors.affiliation: Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, Leuven B-3000, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.affiliation: Department of Chemistry & Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA. Electronic address: kseley@umbc.edu.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Seley-Radtke
authors.affiliation: Department of Pharmaceutical & Toxicological Chemistry, Volgograd State Medical University, Pavshikh Bortsov Sq., 1, Volgograd 400131, Russia.
authors.forename: Mikhail S
authors.initials: MS
authors.lastname: Novikov
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003587:Cytomegalovirus / Q000502:physiology*; D004267:DNA Viruses / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D014645:Herpesvirus 3, Human / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D012328:RNA Viruses / Q000187:drug effects / Q000502:physiology; D013329:Structure-Activity Relationship; D014498:Uracil / Q000737:chemistry*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000081:Acetamides; D000998:Antiviral Agents; D014498:Uracil; C030686:acetamide
keywords: Antiviral; Human cytomegalovirus; Non-nucleoside inhibitor; Uracil; Varicella zoster virus