标题：Discovery of novel pyrazole derivatives as potential anticancer agents in MCL
作者：Ran, Fansheng; Liu, Yang; Zhang, Daoguang; Liu, Meixia; Zhao, Guisen
作者机构：[Ran, Fansheng; Zhang, Daoguang; Liu, Meixia; Zhao, Guisen] Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 Cultur 更多
通讯作者地址：[Zhao, GS]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 Culture West Rd, Jinan 250012, Shandong, Peoples R China 更多
来源：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
关键词：Mantle cell lymphoma; BTK; Irreversible inhibitors; Anticancer; Pyrazole; derivatives
摘要：Mantle cell lymphoma (MCL) is characterized by the translocation t(11;14) (q13;q32), resulting in the overexpression of cyclin-D1. The progression of MCL is an interaction of multitarget and multilink regulation. It has been proven that Bruton's tyrosine kinase (BTK) is commonly overexpressed in MCL, which makes it a focus of targeted therapy for MCL. Irreversible inhibitors usually have great potency, rapid onset of inhibition and long duration of drug action. Herein, structural modification via an open-loop strategy based on lead compound ibrutinib (IBN) was performed, leading to a series of pyrazole derivatives. Compounds 19c, 19'c, 21c and 21'c showed potent effect in MCL cells with IC50 values lower than 1 mu M, and a more than 3-28-fold increase in antiproliferative activity compared with IBN.