1453211-80-7Relevant articles and documents
Discovery and optimization of selective FGFR4 inhibitors via scaffold hopping
Wang, Yikai,Chen, Zhengxia,Dai, Meibi,Sun, Peipei,Wang, Chunqiu,Gao, Yang,Zhao, Haixia,Zeng, Wenqin,Shen, Liang,Mao, Weifeng,Wang, Tian,Hu, Guoping,Li, Jian,Chen, Shuhui,Long, Chaofeng,Chen, Xiaoxin,Liu, Junhua,Zhang, Yang
, p. 2420 - 2423 (2017)
Introduction of a Michael acceptor on a flexible scaffold derived from pan-FGFR inhibitors has successfully yielded a novel series of highly potent FGFR4 inhibitors with selectivity over FGFR1. Due to reduced lipophilicity and aromatic ring count, this series demonstrated improved solubility and permeability. However, plasma instability and fast metabolism limited its potential for in vivo studies. Efforts have been made to address these problems, which led to the discovery of compound (?)-11 with improved stability, CYP inhibition, and good activity/selectivity for further optimization.
2-aminopyrimidine compounds and application thereof
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Paragraph 0188; 0192; 0195; 0196, (2018/09/28)
The invention relates to 2-aminopyrimidine compounds with structures as shown in a formula I which is described in the specification, and pharmaceutically acceptable salts, stereoisomers or prodrug molecules thereof, belonging to the technical field of chemical medicines. The compounds are capable of realizing high-selectivity inhibition of the activity of the FGFR4 protein kinase without inhibition of the activities of other member kinases (i.e., FGFR1, FGFR2 and FGFR3) in the FGFRs family. The compounds can effectively inhibit the growth of tumor cells caused by the abnormity of a FGFR4 signaling pathway, and is applicable to prevention and treatment of transitional proliferative diseases such as tumors in human beings and other mammals caused by the abnormity of the FGFR4 signaling pathway.
2-Aminopyrimidine Derivatives as New Selective Fibroblast Growth Factor Receptor 4 (FGFR4) Inhibitors
Mo, Cheng,Zhang, Zhang,Guise, Christopher P.,Li, Xueqiang,Luo, Jinfeng,Tu, Zhengchao,Xu, Yong,Patterson, Adam V.,Smaill, Jeff B.,Ren, Xiaomei,Lu, Xiaoyun,Ding, Ke
supporting information, p. 543 - 548 (2017/05/19)
A series of 2-aminopyrimidine derivatives were designed and synthesized as highly selective FGFR4 inhibitors. One of the most promising compounds 2n tightly bound FGFR4 with a Kd value of 3.3 nM and potently inhibited its enzymatic activity with an IC50 value of 2.6 nM, but completely spared FGFR1/2/3. The compound selectively suppressed proliferation of breast cancer cells harboring dysregulated FGFR4 signaling with an IC50 value of 0.38 μM. Furthermore, 2n exhibited extraordinary target specificity in a Kinome-wide screen against 468 kinases, with S(35) and S(10) selectivity scores of 0.01 and 0.007 at 1.0 μM, respectively.
NITROGEN-CONTAINING AROMATIC HETEROCYCLIC COMPOUND
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Paragraph 0271; 0329; 0378, (2014/05/25)
Provided is a compound useful as a prophylactic and/or therapeutic agent for bladder cancer. As a result of studies on compounds having FGFR inhibitory action, the present inventors have found that the nitrogen-containing aromatic heterocyclic compounds of the present invention have inhibitory action on FGFR1, FGFR2, and/or FGFR3, particularly, mutant FGFR3, and thus, the present invention has been accomplished. The nitrogen-containing aromatic heterocyclic compound of the present invention can be used as a therapeutic agent for various cancers related to FGFR1, FGFR2, and/or FGFR3, such as lung cancer and hormone therapy-resistant breast cancer, stomach cancer, triple negative breast cancer, endometrial cancer, bladder cancer, and glioblastoma, particularly as a prophylactic and/or therapeutic agent for mutant FGFR3-positive bladder cancer.
