Synthesis of New 5- or 7-Substituted 3-Nitroimidazo[1,2-a]pyridine Derivatives Using S_NAr and Palladium-Catalyzed Reactions To Explore Antiparasitic Structure–Activity Relationships

Abstract

Figure 1 Structures of metronidazole and antikinetoplastid nitroheterocyclic drug compounds

To study the antikinetoplastid structure–activity relationships in a 3-nitroimidazo[1,2-a]pyridine series, we explored the substitution of positions 5 and 7 of the scaffold, developing nucleophilic aromatic substitution reactions and palladium-catalyzed Suzuki–Miyaura, Sonogashira, and Buchwald–Hartwig cross-coupling reactions that had never been reported at these positions in this series. In four steps from 2-amino(bromo)pyridines, 33 original compounds were obtained, allowing a better definition of the antiparasitic pharmacophore.

Key words

nitroaromatic compounds - imidazo[1,2-a]pyridines - kinetoplastids - nucleophilic aromatic substitution - palladium-catalyzed cross-coupling reactions - microwave irradiation

Publication History

Received: 24 October 2023

Accepted after revision: 19 December 2023

Accepted Manuscript online:
19 December 2023

Article published online:
19 January 2024

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