Design, synthesis, and molecular docking study of 3H-imidazole[4,5-c]pyridine derivatives as CDK2 inhibitors

doi:10.1002/ardp.201700381

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	Design, synthesis, and molecular docking study of 3H-imidazole[4,5-c]pyridine derivatives as CDK2 inhibitors
	Wu, Yi-Zhe 2; Ying, Hua-Zhou 2; Xu, Lei 3,4; Cheng, Gang 1; Chen, Jing1 ; Hu, Yong-Zhou 2; Liu, Tao 2; Dong, Xiao-Wu 2
刊名	ARCHIV DER PHARMAZIE
	2018-06
卷号	351 期号:6
关键词	cancer CDK2 inhibitor imidazo[4 5-c]pyridine targeted therapy
ISSN号	0365-6233
DOI	10.1002/ardp.201700381
文献子类	Article
英文摘要	A novel series of imidazo[4,5-c]pyridine-based CDK2 inhibitors were designed from the structure of CYC202 via scaffold hopping strategy. These compounds were synthesized and biologically evaluated for their CDK2 inhibitory and in vitro anti-proliferation potential against cancer cell lines. Several compounds exhibited potent CDK2 inhibition with IC50 values of less than 1 mu M. The most potent compound 5b showed excellent CDK2 inhibitory (IC50=21nM) and in vitro anti-proliferation activity against three different cell lines (HL60, A549, and HCT116). The molecular docking and dynamic studies portrayed the potential binding mechanism between 5b and CDK2, and several key interactions between them were observed, which would be the reason for its potent CDK2 inhibitory and anti-proliferation activities. Therefore, the pyridin-3-ylmethyl moiety would serve as an excellent pharmacophore for the development of novel CDK2 inhibitors for targeted anti-cancer therapy.
资助项目	National Natural Science Foundation of China[81673294] ; State Key Laboratory of Drug Research[SIMM1705KF-08] ; Key New Drug Creation and Manufacturing Program[2018ZX09711002-011-022] ; Science and Technology Planning Project of Zhejiang Province[2016C33067]
WOS关键词	CYCLIN-DEPENDENT KINASES ; CELL-CYCLE ; CANCER-THERAPY ; POTENT ; DISCOVERY ; TARGETS ; AGENTS
WOS研究方向	Pharmacology & Pharmacy ; Chemistry
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000434048300003
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279725]
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
通讯作者	Cheng, Gang; Liu, Tao; Dong, Xiao-Wu
作者单位	1.Zhejiang Chinese Med Univ, Coll Pharmaceut Sci, Hangzhou 311402, Zhejiang, Peoples R China 2.Zhejiang Univ, ZJU ENS Joint Lab Med Chem, Zhejiang Prov Key Lab Anticanc Drug Res, Coll Pharmaceut Sci,Hangzhou Inst Innovat Med, Hangzhou 310058, Zhejiang, Peoples R China; 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China;
推荐引用方式 GB/T 7714	Wu, Yi-Zhe,Ying, Hua-Zhou,Xu, Lei,et al. Design, synthesis, and molecular docking study of 3H-imidazole[4,5-c]pyridine derivatives as CDK2 inhibitors[J]. ARCHIV DER PHARMAZIE,2018,351(6).
APA	Wu, Yi-Zhe.,Ying, Hua-Zhou.,Xu, Lei.,Cheng, Gang.,Chen, Jing.,...&Dong, Xiao-Wu.(2018).Design, synthesis, and molecular docking study of 3H-imidazole[4,5-c]pyridine derivatives as CDK2 inhibitors.ARCHIV DER PHARMAZIE,351(6).
MLA	Wu, Yi-Zhe,et al."Design, synthesis, and molecular docking study of 3H-imidazole[4,5-c]pyridine derivatives as CDK2 inhibitors".ARCHIV DER PHARMAZIE 351.6(2018).