Design, synthesis and evaluation of novel 3,5-disubstituted benzamide derivatives as allosteric glucokinase activators.

ABSTRACT: Glucokinase (GK) is the key enzyme expressed in β-cells of pancreas and liver hepatocytes and helps in the maintenance of blood glucose levels in normal range. Activators of GK are the novel category of drug candidates which activate GK enzyme allosterically and show their antidiabetic activity. A new series of 3,5-disubstituted benzamide analogues was designed, synthesized and evaluated as GK activators by in vitro assay as well as in silico docking studies followed by evaluation of antihyperglycemic activity in animal model. Amongst the synthesized derivatives, compounds 5c, 5f, 5i, 6c, 6e and 6h displayed excellent in vitro GK activation. Compounds 6c and 6e exhibited highest antihyperglycemic activity in oral glucose tolerance tes

SUBMITTER: Grewal AS 

PROVIDER: S-EPMC6661843 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature