A novel series of 4-methyl substituted pyrazole derivatives as potent glucagon receptor antagonists: Design, synthesis and evaluation of biological activities
文献类型：期刊论文
| 作者 | Shu, Shuangjie1,2,3; Dai, Antao4; Wang, Jiang1,2,3 ; Wang, Bin1,2,3; Feng, Yang4; Li, Jia1,2,3; Cai, Xiaoqing4; Yang, Dehua1,4; Ma, Dakota4; Wang, Ming-Wei1,4,5
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| 刊名 | BIOORGANIC & MEDICINAL CHEMISTRY
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| 出版日期 | 2018-05-01 |
| 卷号 | 26期号:8页码:1896-1908 |
| 关键词 | Pyrazole derivatives Glucagon receptor antagonist Docking study Binding pocket |
| ISSN号 | 0968-0896 |
| DOI | 10.1016/j.bmc.2018.02.036 |
| 文献子类 | Article |
| 英文摘要 | A novel series of 4-methyl substituted pyrazole derivatives were designed, synthesized and biologically evaluated as potent glucagon receptor (GCGR) antagonists. In this study, compounds 9q, 9r, 19d and 19e showed high GCGR binding (IC50 = 0.09 mu M, 0.06 mu M, 0.07 mu M and 0.08 mu M, respectively) and cyclic-adenosine monophosphate (cAMP) activities (IC50 = 0.22 mu M, 0.26 mu M, 0.44 mu M and 0.46 mu M, respectively) in cell-based assays. Most importantly, the docking experiment demonstrated that compound 9r formed extensive hydrophobic interactions with the receptor binding pocket, making it justifiable to further investigate the potential of becoming a GCGR antagonist. (C) 2018 Published by Elsevier Ltd. |
| WOS关键词 | PROTEIN-COUPLED RECEPTOR ; ACCURATE DOCKING ; CELL FUNCTION ; A-CELL ; GLUCOSE ; DISCOVERY ; INSULIN ; GLIDE ; IDENTIFICATION ; METABOLISM |
| 资助项目 | National Natural Science Foundation of China[21632008] ; National Natural Science Foundation of China[81620108027] ; National Natural Science Foundation of China[21672231] ; National Health and Family Planning Commission[2012ZX09304-011] ; National Health and Family Planning Commission[2013ZX09401003-005] ; National Health and Family Planning Commission[2013ZX09507001] ; National Health and Family Planning Commission[2013ZX09507-002] ; Shanghai Science and Technology Development Fund[15DZ2291600] ; Shanghai Science and Technology Development Fund[15QA1404400] ; Shanghai Science and Technology Development Fund[14431901200] ; Thousand Talents Program in China[00000000] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000429533300048 |
| 出版者 | PERGAMON-ELSEVIER SCIENCE LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279785]  |
| 专题 | 国家新药筛选中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 药物化学研究室 |
| 通讯作者 | Wang, Ming-Wei; Liu, Hong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China; 4.Natl Ctr Drug Screening, 189 Guo Shou Jing Rd, Shanghai 201203, Peoples R China; 5.Fudan Univ, Sch Pharm, 826 Zhangheng Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shu, Shuangjie,Dai, Antao,Wang, Jiang,et al. A novel series of 4-methyl substituted pyrazole derivatives as potent glucagon receptor antagonists: Design, synthesis and evaluation of biological activities[J]. BIOORGANIC & MEDICINAL CHEMISTRY,2018,26(8):1896-1908. |
| APA | Shu, Shuangjie.,Dai, Antao.,Wang, Jiang.,Wang, Bin.,Feng, Yang.,...&Liu, Hong.(2018).A novel series of 4-methyl substituted pyrazole derivatives as potent glucagon receptor antagonists: Design, synthesis and evaluation of biological activities.BIOORGANIC & MEDICINAL CHEMISTRY,26(8),1896-1908. |
| MLA | Shu, Shuangjie,et al."A novel series of 4-methyl substituted pyrazole derivatives as potent glucagon receptor antagonists: Design, synthesis and evaluation of biological activities".BIOORGANIC & MEDICINAL CHEMISTRY 26.8(2018):1896-1908. |
入库方式： OAI收割
来源：上海药物研究所
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