title: Synthesis and biological evaluation of 1, 2, 4-oxadiazole derivatives as novel GPR119 agonists.
abstract: A series of 1, 2, 4-oxadiazole derivatives have been designed and synthesized, and 25 compounds were evaluated their abilities by the assay of cAMP concentration in GPR119-transfected HEK293T cells. All compounds showed acceptable agonistic effects on GPR119. Among these compounds, 4p exhibited the best agonistic effects with the EC50of 20.6 nm, which was comparable to that of positive control GPR119 agonist GSK1292263. The agonistic activity of these 1,2,4-oxadiazole derivatives led to the establishment of a structure-activity relationship.
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, China.
authors: Suhong
authors: S
authors: Fu
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, China.
authors: Wei
authors: W
authors: Xiang
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, China.
authors: Jinying
authors: J
authors: Chen
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, China.|Division of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China.
authors: Liang
authors: L
authors: Ma
authors: State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center of Biotherapy, West China Hospital, West China Medical School of Sichuan University, Chengdu, China.
authors: Lijuan
authors: L
authors: Chen
mesh_terms: D000242:Cyclic AMP / Q000378:metabolism; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D008698:Mesylates / Q000737:chemistry / Q000378:metabolism; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: C587902:(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)methyl methanesulfonate; C519854:GPR119 protein, human; D007004:Hypoglycemic Agents; D008698:Mesylates; D010069:Oxadiazoles; D043562:Receptors, G-Protein-Coupled; D000242:Cyclic AMP
keywords: GPCR; GPR119; SAR study; agonistic activity; cAMP