title: Benzamide derivatives as dual-action hypoglycemic agents that inhibit glycogen phosphorylase and activate glucokinase.
abstract: A series of benzamide derivatives which can simultaneously inhibit glycogen phosphorylase (GP) and activate glucokinase (GK) were prepared and evaluated. The structure-activity relationships (SAR) of these compounds were also presented. Among these, compounds 12, 13l, 13q, and 13v showed moderate activities towards both GK and GP. Compound 13h inhibited hLGP with an IC(50) of 8.95 microM and activated GK with an EC(50) of 1.87 microM. The possible binding modes of compounds 12, 13l, 13h, and 13q with GP and GK were also explored by molecular docking simulation.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Honglin
authors.initials: H
authors.lastname: Li
authors.forename: Qingzhang
authors.initials: Q
authors.lastname: Zhu
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Leng
authors.forename: Hualiang
authors.initials: H
authors.lastname: Jiang
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D001549:Benzamides / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation; D005941:Glucokinase / Q000378:metabolism*; D024981:Glycogen Phosphorylase / Q000037:antagonists & inhibitors*; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D001549:Benzamides; D007004:Hypoglycemic Agents; C037689:benzamide; D024981:Glycogen Phosphorylase; D005941:Glucokinase