Anti-AIDS agents 81. Design, synthesis, and structure-activity relationship study of betulinic acid and moronic acid derivatives as potent HIV maturation inhibitors.

Journal Article (Journal Article)

In our continuing study of triterpene derivatives as potent anti-HIV agents, different C-3 conformationally restricted betulinic acid (BA, 1) derivatives were designed and synthesized in order to explore the conformational space of the C-3 pharmacophore. 3-O-Monomethylsuccinyl-betulinic acid (MSB) analogues were also designed to better understand the contribution of the C-3' dimethyl group of bevirimat (2), the first-in-class HIV maturation inhibitor, which is currently in phase IIb clinical trials. In addition, another triterpene skeleton, moronic acid (MA, 3), was also employed to study the influence of the backbone and the C-3 modification toward the anti-HIV activity of this compound class. This study enabled us to better understand the structure-activity relationships (SAR) of triterpene-derived anti-HIV agents and led to the design and synthesis of compound 12 (EC(50): 0.0006 microM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.

Full Text

Duke Authors

Cited Authors

  • Qian, K; Kuo, R-Y; Chen, C-H; Huang, L; Morris-Natschke, SL; Lee, K-H

Published Date

  • April 22, 2010

Published In

Volume / Issue

  • 53 / 8

Start / End Page

  • 3133 - 3141

PubMed ID

  • 20329730

Pubmed Central ID

  • PMC2860721

Electronic International Standard Serial Number (EISSN)

  • 1520-4804

Digital Object Identifier (DOI)

  • 10.1021/jm901782m


  • eng

Conference Location

  • United States