2- and 3-substituted imidazo[1,2-a]pyrazines as inhibitors of bacterial type IV secretion

Bioorg Med Chem. 2014 Nov 15;22(22):6459-70. doi: 10.1016/j.bmc.2014.09.036. Epub 2014 Sep 28.

Abstract

A novel series of 8-amino imidazo[1,2-a]pyrazine derivatives has been developed as inhibitors of the VirB11 ATPase HP0525, a key component of the bacterial type IV secretion system. A flexible synthetic route to both 2- and 3-aryl substituted regioisomers has been developed. The resulting series of imidazo[1,2-a]pyrazines has been used to probe the structure-activity relationships of these inhibitors, which show potential as antibacterial agents.

Keywords: 8-Amino imidazo[1,2-a]pyrazine; ATPase inhibitor; Bacterial type IV secretion system; HP0525.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / metabolism
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Binding Sites
  • Gram-Negative Bacteria / metabolism
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry*
  • Imidazoles / metabolism
  • Kinetics
  • Molecular Docking Simulation
  • Protein Binding
  • Protein Structure, Tertiary
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry*
  • Pyrazines / metabolism
  • Structure-Activity Relationship

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Imidazoles
  • Pyrazines
  • imidazo(1,2-a)pyrazine