title: C-Aryl glucoside SGLT2 inhibitors containing a biphenyl motif as potential anti-diabetic agents.
abstract: A series of highly active C-aryl glucoside SGLT2 inhibitors containing a biphenyl motif were designed and synthesized for biological evaluation. Among the compounds tested, compound 16l demonstrated high inhibitory activity against SGLT2 (IC50=1.9 nM) with an excellent pharmacokinetic profile. Further study indicated that the in vivo efficacy of compound 16l was comparable to that of dapagliflozin, suggesting that further development would be worthwhile.
authors.affiliation: State Key Laboratory of Respiratory Disease, Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Respiratory Disease, Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.
authors.forename: Liufeng
authors.initials: L
authors.lastname: Mao
authors.affiliation: State Key Laboratory of Respiratory Disease, Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Respiratory Disease, Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xie
authors.affiliation: Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd, No. 8 Julong North Rd., Xinpu, Lianyungang, Jiangsu 222006, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.affiliation: Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd, No. 8 Julong North Rd., Xinpu, Lianyungang, Jiangsu 222006, China.
authors.forename: Hongjiang
authors.initials: H
authors.lastname: Xu
authors.affiliation: Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd, No. 8 Julong North Rd., Xinpu, Lianyungang, Jiangsu 222006, China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Geng
authors.affiliation: Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd, No. 8 Julong North Rd., Xinpu, Lianyungang, Jiangsu 222006, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd, No. 8 Julong North Rd., Xinpu, Lianyungang, Jiangsu 222006, China.
authors.forename: Chunguang
authors.initials: C
authors.lastname: Xia
authors.affiliation: Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd, No. 8 Julong North Rd., Xinpu, Lianyungang, Jiangsu 222006, China.
authors.forename: Xiquan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Jiangsu Chia-Tai Tianqing Pharmaceutical Co. Ltd, No. 8 Julong North Rd., Xinpu, Lianyungang, Jiangsu 222006, China.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Meng
authors.affiliation: State Key Laboratory of Respiratory Disease, Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Respiratory Disease, Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China. Electronic address: zhao_junling@gibh.ac.cn.
authors.forename: Junling
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Respiratory Disease, Institutes of Biomedicine and Health, Chinese Academy of Science, 190 Kaiyuan Avenue, Guangzhou Science Park, Guangzhou 510530, China. Electronic address: hu_wenhui@gibh.ac.cn.
authors.forename: Wenhui
authors.initials: W
authors.lastname: Hu
mesh_terms: D000818:Animals; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D005951:Glucose Tolerance Test; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D006207:Half-Life; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D051269:Sodium-Glucose Transporter 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051297:Sodium-Glucose Transporter 2 / Q000378:metabolism; D000077203:Sodium-Glucose Transporter 2 Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D001713:Biphenyl Compounds; D005960:Glucosides; D007004:Hypoglycemic Agents; D051269:Sodium-Glucose Transporter 1; D051297:Sodium-Glucose Transporter 2; D000077203:Sodium-Glucose Transporter 2 Inhibitors; C000605553:2-(3-((1,1'-biphenyl)-4-ylmethyl)-4-methylphenyl)-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol; C010574:biphenyl
keywords: Biphenyl; C-Aryl glucoside; SGLT2 inhibitor; Type 2 diabetes