Anti-AIDS Agents 69. Moronic Acid and Other Triterpene Derivatives as Novel Potent Anti-HIV Agents
- 15 August 2006
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 49 (18), 5462-5469
- https://doi.org/10.1021/jm0601912
Abstract
In a continuing structure−activity relationship study of potent anti-HIV agents, seven new triterpene derivatives were designed, synthesized, and evaluated for in vitro antiviral activity. Among them, moronic acid derivatives 19, 20, and 21 showed significant activity in HIV-1 infected H9 lymphocytes. Compounds 19 and 20 were also evaluated against HIV-1 NL4-3 and drug resistant strains in the MT-4 cell line. Compounds 19 and 20 showed better antiviral profiles than the betulinic acid analogue 8 (PA-457), which has successfully completed a Phase IIa clinical trial. Compound 20 showed potent anti-HIV activity with EC50 values of 0.0085 μM against NL4-3, 0.021 μM against PI-R (a multiple protease inhibitor resistant strain), and 0.13 μM against FHR-2 (an HIV strain resistant to 8). Promising compound 20 has become a new lead for modification, and further development of 20-related compounds as clinical trial candidates is warranted.Keywords
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