title: Synthesis and antiviral activity of 1,3-disubstituted uracils against HIV-1 and HCMV.
abstract: The development of new non-nucleoside reverse transcriptase inhibitors (NNRTIs) is an efficient strategy for finding new therapeutic agents against human immunodeficiency virus (HIV). A large number of 6-substituted uracil derivatives have been prepared in order to explore new NNRTIs. However, there are few approaches to anti-HIV agents from 1,3-disubstituted uracil derivatives. Therefore, we tried to prepare several 1,3-disubstituted uracils, which were easily obtainable from uracil by preparation under alkali and Mitsunobu conditions, and examined their antiviral activity against HIV-1 and human cytomegalovirus (HCMV). We found that 1-benzyl-3-(3,5-dimethylbenzyl)uracil and 1-cyanomethyl-3-(3,5-dimethylbenzyl)-4-thiouracil showed powerful inhibition against HCMV and HIV-1, respectively.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan. maruyama@phoenix.ac.jp
authors.forename: Tokumi
authors.initials: T
authors.lastname: Maruyama
authors.forename: Shigetada
authors.initials: S
authors.lastname: Kozai
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yamasaki
authors.forename: Myriam
authors.initials: M
authors.lastname: Witvrouw
authors.forename: Christophe
authors.initials: C
authors.lastname: Pannecouque
authors.forename: Jan
authors.initials: J
authors.lastname: Balzarini
authors.forename: Robert
authors.initials: R
authors.lastname: Snoeck
authors.forename: Graciella
authors.initials: G
authors.lastname: Andrei
authors.forename: Erik
authors.initials: E
authors.lastname: De Clercq
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003587:Cytomegalovirus / Q000187:drug effects*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013889:Thiouracil / Q000031:analogs & derivatives; D014498:Uracil / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D014498:Uracil; D013889:Thiouracil