New Betulinic Acid Derivatives for Bevirimat-Resistant Human Immunodeficiency Virus Type-1

作者：Dang Zhao; Ho Phong; Zhu Lei; Qian Keduo; Lee Kuo Hsiung; Huang Li; Chen Chin Ho^*

来源：Journal of Medicinal Chemistry, 2013, 56(5): 2029-2037.

DOI：10.1021/jm3016969

Bevirimat (1, BVM) is an anti-HIV agent that blocks HIV-1 replication by interfering with HIV-1 Gag-SP1 processing at a late stage of viral maturation. However, clinical trials of 1 have revealed a high baseline drug resistance that is attributed to naturally occurring polymorphisms in HIV-1 Gag. To overcome the drug resistance, 28 new derivatives of 1 were synthesized and tested against compound 1-resistant (BVM-R) HIV-1 variants. Among them, compound 6 exhibited much improved activity against several HIV-1 strains carrying BVM-R polymorphisms. Compound 6 was at least 20-fold more potent than 1 against the replication of NL4-3/V370A, which carries the most prevalent clinical BVM-R polymorphism in HIV-1 Gag-SP1. Thus, compound 6 merits further development as a potential anti-AIDS clinical trial candidate.

• 出版日期2013-3-14
• 单位中国医科大学