2. Academic Validation
  3. Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents

Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents

  • Bioorg Med Chem. 2013 Sep 15;21(18):5900-6. doi: 10.1016/j.bmc.2013.06.061.
Norikazu Sakakibara 1,  Takayuki Hamasaki,  Masanori Baba,  Yosuke Demizu,  Masaaki Kurihara,  Kohji Irie,  Masatoshi Iwai,  Eriko Asada,  Yoshihisa Kato,  Tokumi Maruyama
Affiliations

Affiliation

  • 1 Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, Sanuki City, Japan.
PMID: 23916148 DOI: 10.1016/j.bmc.2013.06.061
Abstract

A novel series of uracil derivatives with a 3,5-dimethylbenzyl group at the N(3)-position were synthesized and evaluated as non-nucleoside HIV-1 Reverse Transcriptase inhibitors. Some of these compounds showed good-to-moderate activity with EC50 values in the submicromolar range. Among them, compound 10c showed significant potency against HIV-1 activity with an EC50 value of 0.03 μM and a high selectivity index of 2863. Preliminary structure-activity relationships and molecular modeling analyses were used to explore the major interactions between HIV-1 Reverse Transcriptase and the potent inhibitor 10c, which may serve as an important lead for further optimization.

Keywords

Anti-HIV-1 agents; HIV-1 RT; Molecular modeling analysis; NNRTIs; Uracil analogs.

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