2. Academic Validation
  3. Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity

Structural modifications of 5,6-dihydroxypyrimidines with anti-HIV activity

  • Bioorg Med Chem Lett. 2012 Dec 1;22(23):7114-8. doi: 10.1016/j.bmcl.2012.09.070.
Di-Liang Guo 1,  Xing-Jie Zhang,  Rui-Rui Wang,  Yu Zhou,  Zeng Li,  Jin-Yi Xu,  Kai-Xian Chen,  Yong-Tang Zheng,  Hong Liu
Affiliations

Affiliation

  • 1 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, PR China.
PMID: 23099098 DOI: 10.1016/j.bmcl.2012.09.070
Abstract

A series of 5,6-dihydroxypyrimidine analogs were synthesized and evaluated for their anti-HIV activity in vitro. Among all of the analogs, several compounds exhibited significant anti-HIV activity, especially 1b and 1e, which showed the most potent anti-HIV activity with EC(50) values of 0.14 and 0.15 μM, and TI (therapeutic index) values of >300 and >900, respectively. Further docking studies revealed that the representative compounds 1e and 3a could meet the HIV-1 integrase inhibition minimal requirements of a chelating domain (two metal ions) and an aromatic domain (π-π stacking interactions).

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