Optimization of novel benzofuro[3,2-b]pyridin-2(1H)-one derivatives as dual inhibitors of BTK and PI3K delta
Liu, Linyi1,2; Li, Xinyu1,2; Cheng, Yu1,2; Wang, Lianjian1,2; Yang, Huizhu1,2; Li, Jiurong1,2; He, Siying1,2; Wu, Shuangjie2; Yin, Qianqian3; Xiang, Hua1,2
2019-02-15
Source PublicationEUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
ISSN0223-5234
Volume164Pages:304-316
Status已发表
DOI10.1016/j.ejmech.2018.12.055
AbstractBTK 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.
KeywordDual inhibitor Oncology B-cell malignancies BTK PI3K delta
Indexed BySCI ; IC
Language英语
WOS Research AreaPharmacology & Pharmacy
WOS SubjectChemistry, Medicinal
WOS IDWOS:000458221400020
PublisherELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
WOS KeywordDESIGNED MULTIPLE LIGANDS ; BRUTONS TYROSINE KINASE ; CELL ; IDELALISIB ; DISCOVERY ; IBRUTINIB ; DOCKING ; POTENT ; TARGET ; BCR
Original Document TypeArticle
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Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://kms.shanghaitech.edu.cn/handle/2MSLDSTB/30296
Collection免疫化学研究所_特聘教授组_抗体化学实验室
Corresponding AuthorYin, Qianqian; Xiang, Hua
Affiliation1.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
Corresponding Author AffilicationShanghai Institute for Advanced Immunochemical Studies
Recommended Citation
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.
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