Synthesis and anti-HIV-1 and anti-HCMV activity of 1-substituted 3-(3,5-dimethylbenzyl)uracil derivatives

Chemical & Pharmaceutical Bulletin
Tokumi MaruyamaErik De Clercq

Abstract

3-(3,5-Dimethylbenzyl)uracil (3) was treated with alkyl halides in the presence of alkali to give 1-substituted congeners. Condensation of 3 with alcohols using the Mitsunobu reaction was also employed as an alternative method. The anti-HIV-1 activity of 1-substituted analogues of 3-(3,5-dimethylbenzyl)uracil was evaluated according to previously established procedures. It appeared that the nitrogen of the 1-cyanomethyl group is important for anti-HIV-1 activity, suggesting interaction with the amino acid residue of HIV-1 reverse transcriptase. 1-Arylmethyl derivatives also showed good anti-HIV-1 activity; and that of 2- and 4-picolyl derivatives was particularly excellent. These results were confirmed by Docking Studies using the program, Glide ligand docking jobs, which suggests hydrogen bonding between amide N-H of Lys 101 and nitrogen of the cyanomethyl and picolyl group.

References

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May 1, 1980·The Journal of Infectious Diseases·E De ClercqD Shugar
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Dec 26, 2003·Antiviral Chemistry & Chemotherapy·Tokumi MaruyamaErik De Clercq
Sep 17, 2004·Nature Reviews. Microbiology·Erik De Clercq
Mar 4, 2005·Journal of Medicinal Chemistry·Erik De Clercq

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Citations

Sep 2, 2014·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Norikazu Sakakibara
Dec 11, 2007·Nucleosides, Nucleotides & Nucleic Acids·Tokumi MaruyamaErik De Clercq
Aug 22, 2015·International Journal of Molecular Sciences·Mihai V PutzAdriana Isvoran
Oct 31, 2015·Antiviral Chemistry & Chemotherapy·Norikazu SakakibaraMasanori Baba
Oct 11, 2011·Antiviral Chemistry & Chemotherapy·Yohei IsonoTokumi Maruyama
Mar 27, 2013·Chemical Communications : Chem Comm·Yi-Yun Yu, Gunda I Georg
Aug 21, 2010·Molecular Diversity·Yogesh Y PedgaonkarRadhakrishnan P Iyer
Jan 17, 2015·Chemical Reviews·Valentine G NenajdenkoAleksey V Shastin

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