title: Design, synthesis, structure-activity relationships, and docking studies of pyrazole-containing derivatives as a novel series of potent glucagon receptor antagonists.
abstract: Glucagon receptor antagonists possess a great potential for treatment of type 2 diabetes mellitus. A series of pyrazole-containing derivatives were designed, synthesized and evaluated by biological assays as glucagon receptor antagonists. Most of the compounds exhibited good in vitro efficacy. Two of them, compounds 17f and 17k, displayed relatively potent antagonist effects on glucagon receptors with IC50 values of 3.9 and 3.6μM, respectively. The possible binding modes of 17f and 17k with the cognate receptor were explored by molecular docking simulation.
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China.
authors.forename: Shuangjie
authors.initials: S
authors.lastname: Shu
authors.affiliation: The National Center for Drug Screening, 189 Guo Shou Jing Road, Shanghai 201203, People's Republic of China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Cai
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China; School of Pharmacy, China Pharmaceutical University, Jiangsu, Nanjing 210009, People's Republic of China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: The National Center for Drug Screening, 189 Guo Shou Jing Road, Shanghai 201203, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Feng
authors.affiliation: The National Center for Drug Screening, 189 Guo Shou Jing Road, Shanghai 201203, People's Republic of China.
authors.forename: Antao
authors.initials: A
authors.lastname: Dai
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China; The National Center for Drug Screening, 189 Guo Shou Jing Road, Shanghai 201203, People's Republic of China.
authors.forename: Dehua
authors.initials: D
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China; The National Center for Drug Screening, 189 Guo Shou Jing Road, Shanghai 201203, People's Republic of China. Electronic address: mwwang@simm.ac.cn.
authors.forename: Ming-Wei
authors.initials: MW
authors.lastname: Wang
authors.affiliation: CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, People's Republic of China; School of Pharmacy, China Pharmaceutical University, Jiangsu, Nanjing 210009, People's Republic of China. Electronic address: hliu@simm.ac.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011720:Pyrazoles; D018027:Receptors, Glucagon
keywords: Antagonist; Glucagon receptor; Molecular docking; Pyrazole; Type 2 diabetes mellitus