Anti-AIDS agents 90. novel C-28 modified bevirimat analogues as potent HIV maturation inhibitors.
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 IC(50) 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.
Duke Scholars
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- Virus Replication
- Triterpenes
- Succinates
- Structure-Activity Relationship
- Medicinal & Biomolecular Chemistry
- Humans
- HIV-1
- Drug Stability
- Drug Design
- Cell Line
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Virus Replication
- Triterpenes
- Succinates
- Structure-Activity Relationship
- Medicinal & Biomolecular Chemistry
- Humans
- HIV-1
- Drug Stability
- Drug Design
- Cell Line