New betulinic acid derivatives for bevirimat-resistant human immunodeficiency virus type-1.
作者： Zhao Dang , Phong Ho , Lei Zhu , Keduo Qian , Kuo-Hsiung Lee
DOI: 10.1021/JM3016969
关键词:
摘要: Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with Gag-SP1 processing at a late stage of viral maturation. However, clinical trials 1 have revealed high baseline drug resistance attributed to naturally occurring polymorphisms in Gag. To overcome the resistance, 28 new derivatives were synthesized and tested against compound 1-resistant (BVM-R) variants. Among them, 6 exhibited much improved activity several strains carrying BVM-R polymorphisms. Compound was least 20-fold more potent than NL4-3/V370A, which carries most prevalent polymorphism Gag-SP1. Thus, merits further development as potential anti-AIDS trial candidate.
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