Imidazopyridine

Imidazo[1,2-a]pyridine—an example of imidazopyridine and a core structure of zolpidem and some compounds described below.

The imidazopyridines are a class of drugs defined by their chemical structure. In general, they are GABA_A receptor agonists, however recently proton pump inhibitors, aromatase inhibitors, NSAIDs and other classes of drugs in this class have been developed as well. Despite usually being similar to them in effect, they are not chemically related to benzodiazepines. As such, GABA_A-agonizing imidazopyridines, pyrazolopyrimidines, and cyclopyrrones are sometimes grouped together and referred to as "nonbenzodiazepines." Imidazopyridines include:

Anxiolytics, sedatives and hypnotics (GABA_A receptor positive allosteric modulators):

• Imidazo[1,2-a]pyridines:
  • Alpidem (original brand name Ananxyl)—anxiolytic that was withdrawn from the market worldwide in 1995 due to hepatotoxicity.
  • DS-1—a GABA_A receptor positive allosteric modulator selective for the α₄β₃δ subtype, which is not targeted by other GABAergics such as benzodiazepines or other nonbenzodiazepines.^[1]
  • Necopidem—an anxiolytic. It has not found clinical use.
  • Saripidem—a sedative and anxiolytic. It is not used clinically.
  • TP-003—a subtype-selective partial agonist at GABA_A receptors, binding to GABA_A receptor complexes bearing either α₂, α₃ or α₅ subunits, but only showing significant efficacy at α₃.
  • Zolpidem (original brand name Ambien)—a widely used hypnotic. Generic versions are widely available.
• Imidazo[4,5-c]pyridines:
  • Bamaluzole—an GABA_A receptor-agonizing anticonvulsant that was never marketed.^[2]

Antipsychotics:

• Imidazo[1,2-a]pyridines:
  • Mosapramine (brand name クレミン, Cremin)—an atypical antipsychotic used in Japan.^[3]

Drugs used for peptic ulcer disease (PUD), GERD and gastroprokinetic agents (motility stimulants):

• Imidazo[1,2-a]pyridines:
  • CJ-033466—an experimental gastroprokinetic acting as a selective 5-HT₄ serotonin receptor partial agonist.^[4]
  • Zolimidine—a gastroprotective agent.^[5]
  • Linaprazan—a potassium-competitive acid blocker which demonstrated similar efficacy as esomeprazole in healing and controlling symptoms of GERD patients with erosive esophagitis.^[6]
  • SCH28080—the prototypical potassium-competitive acid blocker which has not found clinical use because of liver toxicity in animal trials and elevated liver enzyme activity in the serum of human volunteers.^[7]
• Imidazo[4,5-b]pyridines:
  • Tenatoprazole—it blocks the gastric proton pump leading to decline of gastric acid production.

NSAIDs, analgesics and antimigraine drugs:

• Imidazo[1,2-a]pyridines:
  • Miroprofen—a derivative of propionic acid.
• Imidazo[4,5-b]pyridines:
  • Telcagepant—a calcitonin gene-related peptide receptor antagonist which was in clinical trials as a remedy for migraine. Its development was terminated.^[8]

Drugs acting on the cardiovascular system:

• Imidazo[1,2-a]pyridines:
  • Olprinone (loprinone)—a cardiac stimulant.^[9]

Drugs for treatment of bone diseases:

• Imidazo[1,2-a]pyridines:
  • Minodronic acid (brand names Bonoteo, Recalbon)— a third-generation bisphosphonate used for the treatment of osteoporosis.^[10]

Antineoplastic agents:

• Imidazo[1,5-a]pyridines:
  • Fadrozole (brand name Afema)—an aromatase inhibitor.
• Imidazo[4,5-c]pyridines:
  • 3-Deazaneplanocin A—S-adenosyl-L-homocysteine synthesis inhibitor and histone methyltransferase EZH2 inhibitor.

References