A concise synthesis of 3-substituted-7-amino-6-carboxyl-8-azachromones.

ABSTRACT: We report on an approach to truncate the tricyclic 5H-chromeno[2,3-b]pyridin-5-one core of amlexanox, an approved drug under investigation for the treatment of obesity, to the bicyclic 4H-pyrano[2,3-b]pyridin-4-one (8-azachromone) core. A short, concise synthesis generates a key intermediate with requisite functionality on the pyridyl A-ring and iodo functionality on the 4-pyrone B-ring upon which palladium-catalyzed cross-coupling and subsequent reactions generate representative analogues. One of these shows a 14.2-fold increase in aqueous solubility over amlexanox.

SUBMITTER: Gan X 

PROVIDER: S-EPMC7442137 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature