Synthesis of spiro[chroman-2,4′-piperidin]-4-one derivatives as acetyl-CoA carboxylase inhibitors

A number of spiro[chroman-2,4′-piperdin]-4-one derivatives ( 38a– m and 43a– j) have been designed, synthesized and screened for in vitro ACC inhibition. In vivo studies of compound 38j has been carried out. Various spiro[chroman-2,4′-piperidin]-4-one derivatives ( 38a– m and 43a– j) have been designed, synthesized and evaluated for in vitro acetyl-CoA carboxylase (ACC) inhibitory activity. Several compounds have shown ACC inhibitory activity in low nanomolar range. Compound 38j reduced the respiratory quotient (RQ) in C57BL/6J mice indicating increase in whole body fat oxidation even in the presence of high carbohydrate diet. Structure–activity relationship (SAR) has been discussed.