Imidazopyridine-based selective and multifunctional ligands of biological targets associated with psychiatric and neurodegenerative diseases

Eur J Med Chem. 2019 Nov 1;181:111569. doi: 10.1016/j.ejmech.2019.111569. Epub 2019 Jul 31.

Abstract

This article provides an overview of compounds based on imidazo[1,2-a]pyridine, imidazo[1,5-a]pyridine, imidazo[4,5-b]pyridine and imidazo[4,5-c]pyridine scaffolds, which act as potent ligands of diverse molecular targets localized in the central nervous system. A literature survey revealed that various imidazopyridines can be powerful modulators of several diseases associated with CNS dysfunction including Alzheimer's disease, Parkinson's disease, schizophrenia, depression or sleeping disorders. A description of target enzymes (e.g., β-secretase, γ-secretase, fatty acid amide hydrolase - FAAH, leucine-rich repeat kinase 2 - LRRK2) and selected receptors (e.g., GABA-A, histamine H3, serotonin 5-HT3, 5-HT4, 5-HT6, dopamine D4, adenosine A2A, orexin), modes of action of imidazopyridine-based ligands and their therapeutic importance is discussed.

Keywords: Imidazo[1,2-a]pyridine; Imidazo[1,5-a]pyridine; Imidazo[4,5-b]pyridine; Imidazo[4,5-c]pyridine; Neurodegenerative disorders; Neurological disorders; Sleeping disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Drug Design*
  • Humans
  • Imidazoles / chemistry*
  • Imidazoles / pharmacology
  • Imidazoles / therapeutic use*
  • Ligands
  • Mental Disorders / drug therapy*
  • Molecular Targeted Therapy
  • Neurodegenerative Diseases / drug therapy*
  • Pyridines / chemistry*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*

Substances

  • Imidazoles
  • Ligands
  • Pyridines
  • imidazopyridine