中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
首页 机构 成果 学者
  
  1. CAS IR Grid
  2. 上海药物研究所
  3. 中国科学院上海药物研究所
  4. 药理学第一研究室
Design, Synthesis, and Structure-Activity Relationship Study of 2-Oxo-3,4-dihydropyrimido[4,5-d]pyrimidines as New Colony Stimulating Factor 1 Receptor (CSF1R) Kinase Inhibitors

文献类型：期刊论文

作者Xun, Qiuju2,3; Zhang, Zhang4; Luo, Jinfeng2; Tong, Linjiang7; Huang, Minhao2,3; Wang, Zhen2; Zou, Jian4; Liu, Yingqiang1,3,7; Xu, Yong2; Xie, Hua7
刊名JOURNAL OF MEDICINAL CHEMISTRY
出版日期2018-03-22
卷号61期号:6页码:2353-2371
ISSN号0022-2623
DOI10.1021/acs.jmedchem.7b01612
文献子类Article
英文摘要Colony stimulating factor 1 receptor kinase (CSF1R) is a well validated molecular target for anticancer drug discovery. Herein, we report the design, synthesis, and structure activity relationship study of 2-oxo-3,4-dihydropyrimido[4,5-d]pyrimidines as new orally bioavailable CSF1R inhibitors. One of the most promising compounds, 3bw, potently inhibits CSF1R kinase with an IC50 value of 3.0 nM, while it is less potent against structurally related epidermal growth factor receptor (EGFR) and other kinases. The kinase inhibition of 3bw was further validated by Western blotting analysis in RAW264.7 macrophages. The molecule also potently blocks macrophage infiltration, abrogates the protumorigenic influences of macrophages, and exhibits reasonable pharmacokinetic profile. Compound 3bw may serve as a new valuable lead compound for future anticancer drug discovery.
WOS关键词TUMOR-ASSOCIATED MACROPHAGES ; 1 DDR1 INHIBITORS ; C-FMS ; BIOLOGICAL EVALUATION ; CSF-1R INHIBITOR ; PROSTATE-CANCER ; FGFR INHIBITORS ; SOLID TUMORS ; FACTOR-I ; DERIVATIVES
资助项目National Natural Science Foundation of China[21572230] ; National Natural Science Foundation of China[81425021] ; National Natural Science Foundation of China[81673285] ; Guangdong Province[2014TQ01R341] ; Guangdong Province[2015A030306042] ; Guangdong Province[2015A030312014] ; Guangdong Province[2016A050502041] ; Guangzhou City[201508030036] ; Jinan University[00000000]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000428356600011
出版者AMER CHEMICAL SOC
源URL[http://119.78.100.183/handle/2S10ELR8/279843]  
专题药理学第一研究室
中科院受体结构与功能重点实验室
新药研究国家重点实验室
通讯作者Lu, Xiaoyun; Ding, Ke
作者单位1.Shanghai Univ, Sch Life Sci, 99 Shangda Rd, Shanghai 200111, Peoples R China
2.Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, State Key Lab Resp Dis, 190 Kaiyuan Ave, Guangzhou 510530, Guangdong, Peoples R China;
3.Univ Chinese Acad Sci, 19 Yuquan Rd, Beijing 100049, Peoples R China;
4.Jinan Univ, Sch Pharm, 601 Huangpu Ave West, Guangzhou 510632, Guangdong, Peoples R China;
5.Guangzhou City Key Lab Precis Chem Drug Dev, Guangzhou 510632, Guangdong, Peoples R China;
6.Minist Educ MOE Peoples Republ China, Int Cooperat Lab Tradit Chinese Med Modernizat &, Guangzhou 510632, Guangdong, Peoples R China;
7.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, 555 Zu Chong Zhi Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China;
推荐引用方式
GB/T 7714		 Xun, Qiuju,Zhang, Zhang,Luo, Jinfeng,et al. Design, Synthesis, and Structure-Activity Relationship Study of 2-Oxo-3,4-dihydropyrimido[4,5-d]pyrimidines as New Colony Stimulating Factor 1 Receptor (CSF1R) Kinase Inhibitors[J]. JOURNAL OF MEDICINAL CHEMISTRY,2018,61(6):2353-2371.
APA Xun, Qiuju.,Zhang, Zhang.,Luo, Jinfeng.,Tong, Linjiang.,Huang, Minhao.,...&Ding, Ke.(2018).Design, Synthesis, and Structure-Activity Relationship Study of 2-Oxo-3,4-dihydropyrimido[4,5-d]pyrimidines as New Colony Stimulating Factor 1 Receptor (CSF1R) Kinase Inhibitors.JOURNAL OF MEDICINAL CHEMISTRY,61(6),2353-2371.
MLA Xun, Qiuju,et al."Design, Synthesis, and Structure-Activity Relationship Study of 2-Oxo-3,4-dihydropyrimido[4,5-d]pyrimidines as New Colony Stimulating Factor 1 Receptor (CSF1R) Kinase Inhibitors".JOURNAL OF MEDICINAL CHEMISTRY 61.6(2018):2353-2371.

入库方式： OAI收割

来源：上海药物研究所

浏览0
下载0
收藏0
其他版本

除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。