14160-93-1Relevant articles and documents
Design, synthesis and biological evaluation of 4-aminopyrimidine-5-cabaldehyde oximes as dual inhibitors of c-Met and VEGFR-2
Qiang, Hao,Gu, Weijie,Huang, DanDan,Shi, Wei,Qiu, Qianqian,Dai, Yuxuan,Huang, Wenlong,Qian, Hai
, p. 3353 - 3358 (2016)
The synergistically collaboration of c-Met/HGF and VEGFR-2/VEGF leads to development of tumor angiogenesis and progression of various human cancers. Therefore, inhibiting both HGF/c-Met and VEGF/VEGFR signaling may provide a novel and effective therapeutic approach for treating patients with abroad spectrum of tumors. Toward this goal, we designed and synthesized a series of derivatives bearing 4-aminopyrimidine-5-cabaldehyde oxime scaffold as potent dual inhibitors of c-Met and VEGFR-2. The cell proliferation assay in vitro demonstrated most target compounds have inhibition potency both on c-Met and VEGFR-2 with IC50values in nanomolar range, especially compound 14i, 18a and 18b. Based on the further enzyme assay in vitro, compound 18a was considered as the most potent one, the IC50s of which were 210?nM and 170?nM for c-Met and VEGFR-2, respectively. Following that, we docked the compound 10 and 18a with the proteins c-Met and VEGFR-2, and interpreted the SAR of these analogs. All the results indicate that 18a is a dual inhibitors of c-Met and VEGFR-2 that holds promising potential.
Discovery and Evaluation of Pyrazolo[3,4-d]pyridazinone as a Potent and Orally Active Irreversible BTK Inhibitor
Zhang, Xuejun,Sheng, Xijun,Shen, Jie,Zhang, Shoubo,Sun, Wenjie,Shen, Chunli,Li, Yi,Wang, Jun,Lv, Huqiang,Cui, Minghui,Zhu, Yuchuan,Huang, Lei,Hao, Dongling,Qi, Zhibo,Sun, Guanglong,Mao, Weifeng,Pan, Yan,Shen, Liang,Li, Xin,Hu, Guoping,Gong, Zhen,Han, Shuhua,Li, Jian,Chen, Shuhui,Tu, Ronghua,Wang, Xuehai,Wu, Chengde
supporting information, p. 1863 - 1868 (2020/01/02)
The identification and lead optimization of a series of pyrazolo[3,4-d]pyridazinone derivatives are described as a novel class of potent irreversible BTK inhibitors, resulting in the discovery of compound 8. Compound 8 exhibited high potency against BTK kinase and acceptable PK profile. Furthermore, compound 8 demonstrated significant in vivo efficacy in a mouse-collagen-induced arthritis (CIA) model.
Preparation methods of JAK inhibitor and salt thereof
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Paragraph 0106; 0110, (2018/03/24)
The present invention relates to preparation methods of a JAK inhibitor and a salt thereof. The preparation method comprises: (1) carrying out a Suzuki coupling reaction on (R)-3-(4-boronic acid-1H-pyrazol-1-yl)-3-cyclopentylpropionitrile and 6-halogen-5-(2-methoxyvinyl)pyrimidin-4-ylamine to generate (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile; and (2)carrying out a protection group removing and ring-closure reaction on the (3R)-cyclopentyl-3-[4-(5-(2-methoxyvinyl)pyrimidin-4-ylamine)pyrazol-1-yl]propionitrile to generate a JAK inhibitor ruxolitinib. According to the present invention, the new ruxolitinib preparation route is provided, wherein each reaction of the route has the high yield, the total yield of the route is high, the purity of theobtained product is good, the post-treatment of the reaction is simple, and column chromatography is not required; by adopting the route, the required raw materials or catalysts and other materials are relatively easy to obtain; and compared to the method in the prior art, the method of the present invention is economical and is suitable for industrial production.
