Design and synthesis of 2-N-substituted indazolone derivatives as non-carboxylic acid glycogen synthase activators

Glycogen synthase (GS) catalyzes the transfer of glucose residues from UDP-glucose to a glycogen polymer chain, a critical step for glucose storage. Patients with type 2 diabetes normally exhibit low glycogen levels and decreased muscle glucose uptake is the major defect in whole body glucose disposal. Therefore, activating GS may provide a potential approach for the treatment of type 2 diabetes. In order to identify non-carboxylic acids GS activators, we designed and synthesized a series of 2-N-alkyl- and 2-N-aryl-indazolone derivatives and studied their activity in activating human GS.     

Rhodium-catalyzed cyclocarbonylation of azobenzene

Carbonylation of azobenzene derivatives catalyzed by rhodium carbonyls in the presence of nitrobenzene as a hydrogen acceptor gave a four-ring heterocyclic product, indazolo[2,1-a]indazole-6,12-dione, in a good yield, which is derived from a novel cyclocarbonylation with C-H bond activation and CO insertion at each benzene nucleus of azobenzene.