Design, synthesis and hypoglycemic activity of α-benzylsuccinic acid derivatives

Based on the SAR of glinide agents, mitiglinide has been modified to study the SAR of glinides.  α-Benzylsuccinic acid derivatives which were designed and synthesized in order to find some more hypoglycemic active agents and further investigate the SAR of this class of compounds.  From ethyl succinate and substituded benzaldehydes, twelve new target compounds were synthesized by codensation, hydrolysis, anhydridization, amidation and hydrogenization reactions, and their hypoglycemic activity were evaluated with glucose oxidase kit.  All the compounds were characterized by elemental analysis, IR, ¹H NMR and ESI-MS.  The preliminary pharmacological test showed that the compounds have good hypoglycemic activity, especially 6c, 6e and 6g, 6e showed the same hypoglycemic potency as nateglinide.