Core chemotype diversification in the HIV-1 entry inhibitor class using field-based bioisosteric replacement

Bioorg Med Chem Lett. 2016 Jan 1;26(1):228-34. doi: 10.1016/j.bmcl.2015.10.080. Epub 2015 Oct 27.

Abstract

Demand remains for new inhibitors of HIV-1 replication and the inhibition of HIV-1 entry is an extremely attractive therapeutic approach. Using field-based bioisosteric replacements, we have further extended the chemotypes available for development in the HIV-1 entry inhibitor class. Moreover, using field-based disparity analysis of the compounds, 3D structure-activity relationships were derived that will be useful in the further development of these inhibitors towards clinical utility.

Keywords: Antiviral; Bioisosteric replacement; Computer-aided drug design; Field-based; HIV-1 envelope protein; SAR analysis; Scaffold-hopping; Structure–activity landscape.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • HIV-1 / drug effects*
  • Hydrophobic and Hydrophilic Interactions
  • Models, Molecular
  • Molecular Structure
  • Static Electricity
  • Structure-Activity Relationship
  • Virus Internalization / drug effects*

Substances

  • Anti-HIV Agents