Expedient solid-phase synthesis of both symmetric and asymmetric diol libraries targeting aspartic proteases

Bioorg Med Chem Lett. 2009 Jul 15;19(14):3945-8. doi: 10.1016/j.bmcl.2009.03.041. Epub 2009 Mar 17.

Abstract

C(2)-symmetric diols have been shown to be highly potent against HIV-1 protease (PR). However, gaining access to these compounds has been hampered by the need of multistep solution-phase reactions which are often tedious and inefficient. In this Letter, we have disclosed a solid-phase strategy for rapid preparation of small molecule-based, symmetric and asymmetric diols as potential HIV-1 protease inhibitors. Upon biological screening, we found one of them, SYM-5, to be a potent and selective inhibitor (K(i)=400 nM) against HIV-1 protease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzamides / chemical synthesis*
  • Benzamides / chemistry
  • Benzamides / pharmacology
  • Combinatorial Chemistry Techniques
  • HIV Protease / chemistry*
  • HIV Protease / metabolism
  • HIV Protease Inhibitors / chemical synthesis*
  • HIV Protease Inhibitors / chemistry
  • HIV Protease Inhibitors / pharmacology
  • Humans
  • Small Molecule Libraries

Substances

  • Benzamides
  • HIV Protease Inhibitors
  • Small Molecule Libraries
  • HIV Protease
  • p16 protease, Human immunodeficiency virus 1