American Chemical Society
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Anti-AIDS Agents 81. Design, Synthesis, and Structure−Activity Relationship Study of Betulinic Acid and Moronic Acid Derivatives as Potent HIV Maturation Inhibitors

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journal contribution
posted on 2010-04-22, 00:00 authored by Keduo Qian, Reen-Yun Kuo, Chin-Ho Chen, Li Huang, Susan L. Morris-Natschke, Kuo-Hsiung Lee
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 (EC50: 0.0006 μM), which displayed slightly better activity than 2 as a HIV-1 maturation inhibitor.