Unknown

Dataset Information

0

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


ABSTRACT: 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 ?M compared with 0.087 ?M 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.

SUBMITTER: Qian K 

PROVIDER: S-EPMC3478670 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

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

Qian Keduo K   Bori Ibrahim D ID   Chen Chin-Ho CH   Huang Li L   Lee Kuo-Hsiung KH  

Journal of medicinal chemistry 20120914 18


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 ant  ...[more]

Similar Datasets

| S-EPMC4704169 | biostudies-other
| S-EPMC8704707 | biostudies-literature
| S-EPMC2906235 | biostudies-literature
| S-EPMC2860721 | biostudies-literature
| S-EPMC2080775 | biostudies-literature
| S-EPMC3171603 | biostudies-literature
| S-EPMC5152578 | biostudies-literature
| S-EPMC6676518 | biostudies-literature
| S-EPMC1635232 | biostudies-literature
| S-EPMC6415679 | biostudies-literature