C2-functionalized imidazo[1,2-a]pyridine: Synthesis and medicinal relevance

Abstract

Imidazo[1,2-a]pyridine is a privileged scaffold in medicinal chemistry with a wide range of biological activities. C3-functionalized derivatives of Imidazo[1,2-a]pyridine having an alkyl/alkenyl or benzyl substituent at the C2 position have been extensively explored for their biological profile as functionalization at the C2 position of imidazopyridine is difficult owing to the stability of electrophilic attack on its C3 position. Furthermore, the synthesis of imidazo[1,2-α]pyridine derivatives from 2-amino pyridine in the presence of nitroalkenes, α-halo ketones, haloalkynes, dibromo-2-phenylethene, and Morita-Baylis-Hillman acetates and bromides of nitroalkenes by customary protocols allow the functionalization mainly at the C3 position. The difficulty of functionalization at the C2 position of imidazo[1,2-α]pyridine, and its passivity toward the electrophilic attack makes it challenging to activate the C(2)-H bond. However, the commercialization of Zolimidine and Miroprofen has further led to the realization of the emerging medicinal potential of C2 functionalized imidazo[1,2-α]pyridines which has been discussed in this mini review.

Graphical Abstract

Keywords:

• C2 functionalization
• imidazopyridines
• miroprofen
• regioselectivity
• zolimidine

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

The authors duly acknowledge the research grant from DST-SERB, India for for supporting this work. PP thanks DST-SERB for TARE fellowship [File No. TAR/2021/000129].