Identification of a 3-aminoimidazo[1,2-a]pyridine inhibitor of HIV-1 reverse transcriptase

Virol J. 2012 Dec 11:9:305. doi: 10.1186/1743-422X-9-305.

Abstract

Background: Despite the effectiveness of highly active antiretroviral therapy (HAART), there remains an urgent need to develop new human immunodeficiency virus type 1 (HIV-1) inhibitors with better pharmacokinetic properties that are well tolerated, and that block common drug resistant virus strains.

Methods: Here we screened an in-house small molecule library for novel inhibitors of HIV-1 replication.

Results: An active compound containing a 3-aminoimidazo[1,2-a]pyridine scaffold was identified and quantitatively characterized as a non-nucleoside reverse transcriptase inhibitor (NNRTI).

Conclusions: The potency of this compound coupled with its inexpensive chemical synthesis and tractability for downstream SAR analysis make this inhibitor a suitable lead candidate for further development as an antiviral drug.

Publication types

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

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Drug Evaluation, Preclinical
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / physiology
  • Humans
  • Imidazoles / chemistry
  • Imidazoles / pharmacology*
  • Pyrazines / chemistry
  • Pyrazines / pharmacology*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Small Molecule Libraries / pharmacology

Substances

  • 3-aminoimidazo(1,2-a)pyrazine
  • Anti-HIV Agents
  • Imidazoles
  • Pyrazines
  • Reverse Transcriptase Inhibitors
  • Small Molecule Libraries
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase