Fluorinated betulinic acid derivatives and evaluation of their anti-HIV activity

  • Bioorg Med Chem Lett. 2016 Jan 1;26(1):68-71. doi: 10.1016/j.bmcl.2015.11.029.
Jizhen Li  1 ,  Masuo Goto  2 ,  Xiaoming Yang  2 ,  Susan L Morris-Natschke  2 ,  Li Huang  3 ,  Chin-Ho Chen  3 ,  Kuo-Hsiung Lee  4
Affiliations
  • 1. Department of Organic Chemistry, College of Chemistry, Jilin University, 2519 Jiefang Road, Changchun 130023, China; Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
  • 2. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States.
  • 3. Surgical Science, Department of Surgery, Duke University Medical Center, Durham, NC 27710, United States.
  • 4. Natural Products Research Laboratories, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, United States; Chinese Medicine Research and Development Center, China Medical University and Hospital, Taichung, Taiwan.
PMID: 26598461 DOI: 10.1016/j.bmcl.2015.11.029
Abstract

Several fluorinated derivatives of the anti-HIV maturation agent bevirimat (1) were synthesized and evaluated for anti-HIV replication activity. The modified positions were the C-2, C-3, C-28, and C-30 positions, either directly on the betulinic acid (2) skeleton or in the attached side chains. Compound 18, which has a trifluoromethyl group added to C-30 of its isopropenyl group, exhibited similar potency to 1 against HIV-1NL4-3. In total, our current studies support our prior conclusion that C-30 allylic modification is unlikely to be a pharmacophore for anti-HIV activity, but could be a meaningful route to manipulate Other properties of 2-related compounds.

Keywords
Anti-HIV activity; Bevirimat; Fluorinated betulinic acid derivatives.