Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3K delta

doi:10.1016/j.ejmech.2018.12.055

	Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3K delta
	Liu, Linyi 1,2; Li, Xinyu 1,2; Cheng, Yu 1,2; Wang, Lianjian 1,2; Yang, Huizhu 1,2; Li, Jiurong 1,2; He, Siying 1,2; Wu, Shuangjie 2; Yin, Qianqian3 ; Xiang, Hua 1,2
	2019-02-15
发表期刊	EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0223-5234
卷号	164 页码:304-316
发表状态	已发表
DOI	10.1016/j.ejmech.2018.12.055
摘要	BTK and PI3K delta play crucial roles in the progression of leukemia, and studies confirmed that the dual inhibition against BTK and PI3K delta could provide superior anticancer agents to single targeted therapies. Herein, a new series of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives were optimized based on a BTK/PI3K delta inhibitor 2 designed by our group. Biological studies clarified that compound 6f exhibited the most potent inhibitory activity (BTK: IC50 = 74 nM; PI3K delta: IC50 = 170 nM) and better selectivity than 2. Moreover, 6f significantly inhibited the proliferation of Raji and Ramos cells with IC50 values of 2.1 mu M and 2.65 mu M respectively by blocking BTK and PI3K signaling pathways. In brief, 6f possessed of the potency for further optimization as an anti-leukemic drug by inhibiting BTK and PI3K delta kinase. (C) 2018 Elsevier Masson SAS. All rights reserved.
关键词	Dual inhibitor Oncology B-cell malignancies BTK PI3K delta
收录类别	SCI ; SCIE ; IC
语种	英语
WOS研究方向	Pharmacology & Pharmacy
WOS类目	Chemistry, Medicinal
WOS记录号	WOS:000458221400020
出版者	ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS关键词	DESIGNED MULTIPLE LIGANDS ; BRUTONS TYROSINE KINASE ; CELL ; IDELALISIB ; DISCOVERY ; IBRUTINIB ; DOCKING ; POTENT ; TARGET ; BCR
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/30296
专题	免疫化学研究所_特聘教授组_抗体化学实验室
通讯作者	Yin, Qianqian; Xiang, Hua
作者单位	1.China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, 24 Tongjiaxiang, Nanjing 210009, Peoples R China 2.China Pharmaceut Univ, Sch Pharm, Dept Med Chem, 24 Tongjiaxiang, Nanjing 210009, Peoples R China 3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
通讯作者单位	免疫化学研究所
推荐引用方式 GB/T 7714	Liu, Linyi,Li, Xinyu,Cheng, Yu,et al. Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3K delta[J]. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,2019,164:304-316.
APA	Liu, Linyi.,Li, Xinyu.,Cheng, Yu.,Wang, Lianjian.,Yang, Huizhu.,...&Xiang, Hua.(2019).Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3K delta.EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY,164,304-316.
MLA	Liu, Linyi,et al."Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3K delta".EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY 164(2019):304-316.