Synthesis and biological evaluation of novel HIV-1 protease inhibitors using tertiary amine as P2-ligands

Bioorg Med Chem Lett. 2015 May 1;25(9):1880-3. doi: 10.1016/j.bmcl.2015.03.047. Epub 2015 Mar 24.


A series of tertiary amine derivatives exhibiting potent HIV-1 protease inhibiting properties were identified. These novel inhibitors were designed based on the structure of Darunavir with modification on the P2 and P2' position. This effort led to discovery of 35e and 38e, which exhibited excellent HIV-1 protease inhibition with IC50 values of 15 nM and 64 nM, respectively.

Keywords: Darunavir; HAART; HIV-1 protease; Inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry*
  • Amines / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Discovery
  • HIV Protease / metabolism*
  • HIV Protease Inhibitors / chemical synthesis*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology*
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Ligands
  • Molecular Structure
  • Structure-Activity Relationship


  • Amines
  • HIV Protease Inhibitors
  • Ligands
  • HIV Protease