Anti-AIDS agents 90. novel C-28 modified bevirimat analogues as potent HIV maturation inhibitors

Journal Article

In a continuing study of bevirimat (2), the anti-HIV-maturation clinical trials agent, 28 new betulinic acid (BA, 1) derivatives were designed and synthesized. Among these compounds, 17, with a C-28 MEM ester moiety, and 22, with a C-28 ethyl hexanoate, increased the anti-HIV replication activity compared with 2 by 2-fold while compounds 40, 41, 48, and 49, with C-28 piperazine or piperidine amide substitutions, increased the activity by 3- to 15-fold. The best new compound, 41, exhibited an anti-HIV IC50 of 0.0059 μM compared with 0.087 μM for 2. All of the active compounds showed only antimaturation effects, as confirmed by TZM-bl assay, in blocking the HIV replication. The results suggest that proper C-28 substitutions can further enhance the antimaturation activity of 2 without any antientry effects. Thus, 41 may serve as a promising new lead for development of anti-AIDS clinical trial candidates. © 2012 American Chemical Society.

Full Text

Duke Authors

Cited Authors

  • Qian, K; Bori, ID; Chen, C-H; Huang, L; Lee, K-H

Published Date

  • 2012

Published In

Volume / Issue

  • 55 / 18

Start / End Page

  • 8128 - 8136

PubMed ID

  • 22978745

International Standard Serial Number (ISSN)

  • 0022-2623

Digital Object Identifier (DOI)

  • 10.1021/jm301040s