Xi:Irritant;6574-15-8Relevant articles and documents
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Bradley,Robinson
, p. 1254,1261 (1932)
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Ligand compound for copper catalyzed aryl halide coupling reaction, catalytic system and coupling reaction
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Paragraph 0086-0091; 0097, (2021/05/29)
The invention provides a ligand compound capable of being used for copper catalyzed aryl halide coupling reaction, the ligand compound is a three-class compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group, and the invention also provides a catalytic system for the aryl halide coupling reaction. Thecatalytic system comprises a copper catalyst, a compound containing a 2-(substituted or non-substituted) aminopyridine nitrogen-oxygen group adopted as a ligand, alkali and a solvent, and meanwhile, the invention also provides a system for the aryl halide coupling reaction adopting the catalyst system. The compound containing the 2-(substituted or non-substituted) aminopyridine nitrogen oxygen group can be used as the ligand for the copper catalyzed aryl chloride coupling reaction, and the ligand is stable under a strong alkaline condition and can well maintain catalytic activity when being used for the copper-catalyzed aryl chloride coupling reaction. In addition, the copper catalyst adopting the compound as the ligand can particularly effectively promote coupling of copper catalyzed aryl chloride and various nucleophilic reagents which are difficult to generate under conventional conditions, C-N, C-O and C-S bonds are generated, and numerous useful small molecule compounds are synthesized. Therefore, the aryl halide coupling reaction has a very good large-scale application prospect by adopting the copper catalysis system of the ligand.
Optimization of WZ4003 as NUAK inhibitors against human colorectal cancer
Yang, Huali,Wang, Xiaobing,Wang, Cheng,Yin, Fucheng,Qu, Lailiang,Shi, Cunjian,Zhao, Jinhua,Li, Shang,Ji, Limei,Peng, Wan,Luo, Heng,Cheng, Maosheng,Kong, Lingyi
, (2020/12/15)
NUAK, the member of AMPK (AMP-activated protein kinase) family of protein kinases, is phosphorylated and activated by the LKB1 (liver kinase B1) tumor suppressor protein kinase. Recent work has indicated that NUAK1 is a key component of the antioxidant stress response pathway, and the inhibition of NUAK1 will suppress the growth and survival of colorectal tumors. As a promising target for anticancer drugs, few inhibitors of NUAK were developed. With this goal in mind, based on NUAK inhibitor WZ4003, a series of derivatives has been synthesized and evaluated for anticancer activity. Compound 9q, a derivative of WZ4003 by removing a methoxy group, was found to be the most potential one with stronger inhibitory against NUAK1/2 enzyme activity, tumor cell proliferation and inducing apoptosis of tumor cells. By in vivo efficacy evaluations of colorectal SW480 xenografts, 9q suppresses tumor growth more effectively with an excellent safety profile in vivo and is therefore seen as a suitable candidate for further investigation.
Discovery and SARs of 5-Chloro- N4-phenyl- N2-(pyridin-2-yl)pyrimidine-2,4-diamine Derivatives as Oral Available and Dual CDK 6 and 9 Inhibitors with Potent Antitumor Activity
Wang, Yang,Chen, Xing,Yan, Yaoyao,Zhu, Xiaochen,Liu, Mingming,Liu, Xinhua
, p. 3327 - 3347 (2020/04/08)
Cyclin-dependent kinases (CDKs) are promising therapeutic targets for cancer therapy. Herein, we describe our efforts toward the discovery of a series of 5-chloro-N4-phenyl-N2-(pyridin-2-yl)pyrimidine-2,4-diamine derivatives as dual CDK6 and 9 inhibitors. Intensive structural modifications lead to the identification of compound 66 as the most active dual CDK6/9 inhibitor with balancing potency against these two targets and good selectivity over CDK2. Further biological studies revealed that compound 66 was directly bound to CDK6/9, resulting in suppression of their downstream signaling pathway and inhibition of cell proliferation by blocking cell cycle progression and inducing cellular apoptosis. More importantly, compound 66 significantly inhibited tumor growth in a xenograft mouse model with no obvious toxicity, indicating the promising therapeutic potential of CDK6/9 dual inhibitors for cancer treatment. Therefore, the above results are of great importance in the development of dual CDK6/9 inhibitors for cancer therapy.
