Anti-AIDS agents 49. Synthesis, anti-HIV, and anti-fusion activities of IC9564 analogues based on betulinic acid

J Med Chem. 2002 Sep 12;45(19):4271-5. doi: 10.1021/jm020069c.

Abstract

The betulinic acid derivative IC9564 inhibits human immunodeficiency virus (HIV)-1 entry. Among a series of IC9564 derivatives, 5 and 20 were the most promising compounds against HIV infection with EC(50) values of 0.33 and 0.46 microM, respectively. Both compounds inhibited syncytium formation with EC(50) values of 0.40 and 0.33 microM, respectively. The comparable EC(50) values in the two assays suggested that these compounds are fusion inhibitors. The structure-activity relationship data also indicated that a double bond in IC9564 can be eliminated and the statine moiety can be replaced with L-leucine while retaining anti-HIV activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amides / chemical synthesis*
  • Amides / chemistry
  • Amides / pharmacology
  • Animals
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Betulinic Acid
  • COS Cells
  • Chlorocebus aethiops
  • HIV Fusion Inhibitors / chemical synthesis
  • HIV Fusion Inhibitors / chemistry
  • HIV Fusion Inhibitors / pharmacology
  • HIV-1*
  • Leucine / analogs & derivatives
  • Leucine / chemical synthesis*
  • Leucine / chemistry
  • Leucine / pharmacology
  • Membrane Fusion / drug effects
  • Pentacyclic Triterpenes
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis*
  • Triterpenes / chemistry*
  • Triterpenes / pharmacology

Substances

  • Amides
  • Anti-HIV Agents
  • HIV Fusion Inhibitors
  • IC9564
  • N'-(N-(3-hydroxybetulin-28-oyl)-11-aminoundecanoyl)leucine
  • N'-(N-(3-hydroxydihydrobetulin28-oyl)-8-aminooctanoyl)-4-amino-3-hydroxy-6-methylheptanoic acid
  • Pentacyclic Triterpenes
  • Triterpenes
  • Leucine
  • Betulinic Acid