title: C-Aryl Glucosides with Substituents at the Distal Aryl Ring as Sodium-Dependent Glucose Cotransporter Inhibitors for the Treatment of Diabetes Mellitus.
abstract: A series of novel C-aryl glucosides with various substituents at the distal aryl ring have been synthesized and evaluated for hypoglycemic effect in normal and diabetic mice and in type 2 diabetic rats. The results indicated that introduction of electron-donating group at the distal aryl ring could improve glucose tolerance in normal mice, whereas introduction of electron-withdrawing group at this position could deteriorate. The urinary glucose excretion was significantly increased after glucose (3 g/kg) administration in normal mice with the treatment of 13c. Moreover, compound 13c could reduce fed blood glucose levels in a dose-dependent manner in type 2 diabetic rats, showed a remarkable antihyperglycemic effect with 2 weeks of treatment in diabetic mice, and might be a promising drug candidate for the treatment of diabetes mellitus.
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Xuekun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.|Tianjin Medical University Metabolic Hospital, Tong'andao66, Tianjin, 300070, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.|Medical and Health Management Department, Jiangsu Food & Pharmaceutical Science College, 4 Meicheng South Road, Higher Education Area, Huaian, Jiangsu, 223003, China.
authors.forename: Baowei
authors.initials: B
authors.lastname: Yang
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Wenlong
authors.initials: W
authors.lastname: Huang
authors.affiliation: Centre of Drug Discovery, State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism; D015195:Drug Design; D005960:Glucosides / Q000737:chemistry / Q000494:pharmacology*; D006029:Glycosuria / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D001786:Blood Glucose; D005960:Glucosides; D007004:Hypoglycemic Agents; D051247:Sodium-Glucose Transport Proteins
keywords: C-aryl glucosides; diabetes mellitus type 2; sodium-glucose cotransporters