SAR study of 5-alkynyl substituted quinazolin-4(3H)-ones as phosphoinositide 3-kinase delta (PI3Kδ) inhibitors

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• 作者：Manman Wei^a ; ^c ; ¹ ; Xi Zhang^b ; ¹ ; Xiang Wang^b ; Zilan Song^a ; Jian Ding^b ; Ling-Hua Meng^b ; ^{lhmeng@simm.ac.cn} ; Ao Zhang^a ; ^c ; ^{aozhang@simm.ac.cn}
• 关键词：Chronic lymphocytic leukemia ; PI3Kδ ; Structure-activity relationship ; 5-Alkynyl ; Quinazolinone
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：5 January 2017
• 年：2017
• 卷：125
• 期：Complete
• 页码：1156-1171
• 全文大小：2684 K
• 卷排序：125

文摘

PI3Kδ is an appealing target for chronic lymphocytic leukemia (CLL). Diverse alkynyls were introduced to quinazolin-4(3H)-one PI3Kδ inhibitors. 8d showed high potency against PI3Kδ (3.82 nM) and SU-DHL-6 cells (7.60 nM). 8d resulted in reduction of phosphorylation of both Akt (S473) and S6k1 (T389). 8d also showed potent activity as well against T lymphoblast MOLT-4.