Discovery of 4-cyclopropyl-3-(2-((1-cyclopropyl-1H-pyrazol-4-yl) amino) quinazolin-6-yl)-N-(3-(trifluoromethyl) phenyl) benzamides as potent discoidin domain receptor inhibitors for the treatment of idiopathic pulmonary fibrosis

作     者：Qi Wang Bixi Tang Dandan Sun Ying Dong Yinchun Ji Huanyu Shi Liwei Zhou Yueyue Yang Menglan Luo Qian Tan Lin Chen Yue Dong Cong Li Rongrong Xie Yi Zang Jingkang Shen Bing Xiong Jia Li Danqi Chen 

作者机构：Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Division of Anti-tumor PharmacologyState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China University of Chinese Academy of SciencesBeijing 100049China Center for Supramolecular Chemistry and Catalysis and Department of ChemistryCollege of SciencesShanghai UniversityShanghai 200444China Department of PharmacologySchool of PharmacyFudan UniversityShanghai 201203China School of Chinese Materia MedicaNanjing University of Chinese MedicineNanjing 210023China Department of Pulmonary and Critical Care MedicineShanghai Fifth People’s HospitalFudan UniversityShanghai 200240China Department of ChemistryCollege of SciencesShanghai UniversityShanghai 200444China School of Pharmaceutical Science and TechnologyHangzhou Institute for Advanced StudyUCASHangzhou 310024China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2022年第12卷第4期

页      面：1943-1962页

核心收录：

学科分类：1007[医学-药学(可授医学、理学学位)] 100701[医学-药物化学] 10[医学] 

基　　金：This research has been financially supported by grants from the Strategic Priority Research Program of the Chinese Academy of Sciences(Grant No.XDA12020323) the National Science&Technology Major Project“Key New Drug Creation and Manufacturing Program”of China(Grant No.2018ZX09711002-004-009) the Strategic Priority Research Program of Chinese Academy of Sciences(No.SIMM010203) Institutes for Drug Discovery and Development,Chinese Academy of Sciences(No.CASIMM0120215009) National Natural Science Foundation of China(No.U1703235) Shanghai Science and Technology Development Funds(18431907100,China) 

主　　题：Idiopathic pulmonary fibrosis Discoidin domain receptor Kinase Inhibitor Docking 

摘      要：Idiopathic pulmonary fibrosis(IPF)is a chronic fatal lung disease with a median survival time of 3–5 *** diagnosis,limited clinical therapy and high mortality together indicate that the development of effective therapeutics for IPF is an urgent *** recent years,it was reported that DDRs are potential targets in anti-fibrosis *** on previous work we carried out further structure modifications and led to a more selective inhibitor 47 by averting some fibrosis-unrelated kinases,such as RET,AXL and *** profiling of compound 47 has demonstrated that it has potent DDR1/2 inhibitory activities,low toxicity,good pharmacokinetic properties and reliable in vivo anti-fibrosis ***,we confirmed that discoidin domain receptors are promising drug targets for IPF,and compound 47 would be a promising candidate for further drug development.