Recent Progress in the Pharmacology of Imidazo[1,2-a]pyridines

Abstract

Imidazo[1,2-a]pyridine is a bicyclic system with a bridgehead nitrogen atom, of growing interest in medicinal chemistry. The paper deals with the recent progress realised in the comprehension of the pharmacological properties of this scaffold. From the many imidazo[1,2-a]pyridine analogues described in the literature, those discussed herein will be presented in three parts concerning first the enzyme inhibitors, then the receptor ligands and finally the anti-infectious agents.

Copper‐Catalyzed Aerobic Oxidative CH Functionalization of Substituted Pyridines: Synthesis of Imidazopyridine Derivatives

“…In 2010, Barluenga, Tomµs and co-workers reported an efficient copper-catalyzed annulation of pyridines with highly active alkenyldiazoacetates leading to indolizines. [4] ImidazoA C H T U N G T R E N N U N G [1,2-a]pyridine derivatives have shown diverse biological and pharmaceutical activities, [5] for example, they exhibit anticancer, antiviral, antiparasitic, and anti-HIV properties, [6] and some compounds have been used as NO synthase and GABAA inhibitors, and l-DOPA and dopamine pro-drugs. [7] In particular, the imidazoA C H T U N G T R E N N U N G [1,2-a]pyridine unit is the core structure of many drugs currently on the market.…”

“…[11] Accordingly, various efficient and useful approaches to imidazopyridine derivatives have been developed in which substituted 2-aminopyridines are usually employed as the starting materials. [5,12] Compared with 2-aminopyridines, pyridines are more readily available and inexpensive. To the best of our knowledge, the annulation of pyridines to form imidazoA C H T U N G T R E N N U N G [1,2-a]pyridine derivatives by transition-metal-catalyzed C À H functionalization has not been reported.…”

Tandem Amination/Cycloisomerization of Aryl Propargylic Alcohols with 2‐Aminopyridines as an Expedient Route to Imidazo[1,2‐a]pyridines

“…[6] In principle, a combination of direct propargylic substitution and subsequent cycloisomerization could open a new window of tandem reactions for the synthesis of various heterocyclic structures. [7] Imidazo[1,2-a]pyridine is recognized as a "drug prejudice" scaffold because of its broad occurrence in a number of drug candidates and clinical drugs, which include Zolpidem, Alpidem, Olprinone, and Minodronic acid, [8] and several synthetic approaches for the scaffold are available. [9] However, these approaches can suffer from inappropriate substitution patterns, precursors that are difficult to obtain, poor atom economics, and sluggish reactions (up to 10 d).…”

Recent synthetic scenario on imidazo[1,2-a]pyridines chemical intermediate

“…3), such as alpidem 1.1 (anxiolytic) [8], zolpidem 1.2 (hypnotic, to treat insomnia) [9], necopidem 1.3 [10], saripidem 1.4 (sedative and anxiolytic), zolimidine 1.5 (anti-ulcer, used for treatment peptic ulcer) [11], olprinone 1.6 (to treat acute heart failure) [12] and minodronic acid 1.7 (to treat anxiety, heart failure, osteoporosis) [13]. This basic structure also exists in GSK812397 1.8 (HIV infection) [14], PI3Ka inhibitors 1.9, mGlu2 receptors 1.10 [15], TNF-a inhibitors 1.11 [16] and insecticide activity against pea aphids 1.12 [17] Furthermore, this basic core moiety is obtained in many pharmaceutical compounds (Fig.…”