Synthesis and antiviral activity of 1,3-disubstituted uracils against HIV-1 and HCMV.
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.
Maruyama
Tokumi
T
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan. maruyama@phoenix.ac.jp
Kozai
Shigetada
S
Yamasaki
Tetsuo
T
Witvrouw
Myriam
M
Pannecouque
Christophe
C
Balzarini
Jan
J
Snoeck
Robert
R
Andrei
Graciella
G
De Clercq
Erik
E
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*
D000998:Antiviral Agents; D018894:Reverse Transcriptase Inhibitors; D014498:Uracil; D013889:Thiouracil