Synthesis, Crystal and Biological Activity of 3-(2,4-Difluorobenzyl)-5-(p-tolyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-amine

摘要
图/表
参考文献
相关文章 (15)

全文: PDF (621 KB) HTML (1 KB)
输出: BibTeX | EndNote (RIS)

摘要 The title compound 3-(2,4-difluorobenzyl)-5-(p-tolyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin- 2-amine (6) was synthesized by the condensation of 4,4,4-trifluoro-1-(p-tolyl)butane-1,3-dione (5) with 4-(2,4-difluorobenzyl)-1H-pyrazole-3,5-diamine (4). The latter was prepared from 2,4-difluorobenzaldehyde (1) and malononitrile through Knoevenagel condensation and NaBH3CN reduction and then cyclisation with hydrazine hydrate. The crystal structure of the title compound was determined and its crystal belongs to the triclinic system, space group P with a = 5.4939(9), b = 10.6480(17), c = 16.508(3) Å, α = 93.226(2)°, β = 97.050(2)° and γ = 98.325(2)°. In addition, the compound possesses distinct effective inhibition on the proliferation of MKN45, HT-29 and K562 cell lines with IC50 values of 5.57, 7.72 and 0.83 μM, respectively, displaying promising anticancer activity.

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	季晓晖
	赵娟
	卢久富
	葛红光

关键词 ： pyrazolo[1,5-a]pyrimidine, synthesis, X-ray diffraction, antitumor activity

Abstract：The title compound 3-(2,4-difluorobenzyl)-5-(p-tolyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin- 2-amine (6) was synthesized by the condensation of 4,4,4-trifluoro-1-(p-tolyl)butane-1,3-dione (5) with 4-(2,4-difluorobenzyl)-1H-pyrazole-3,5-diamine (4). The latter was prepared from 2,4-difluorobenzaldehyde (1) and malononitrile through Knoevenagel condensation and NaBH3CN reduction and then cyclisation with hydrazine hydrate. The crystal structure of the title compound was determined and its crystal belongs to the triclinic system, space group P with a = 5.4939(9), b = 10.6480(17), c = 16.508(3) Å, α = 93.226(2)°, β = 97.050(2)° and γ = 98.325(2)°. In addition, the compound possesses distinct effective inhibition on the proliferation of MKN45, HT-29 and K562 cell lines with IC50 values of 5.57, 7.72 and 0.83 μM, respectively, displaying promising anticancer activity.

Key words： pyrazolo[1,5-a]pyrimidine synthesis X-ray diffraction antitumor activity

收稿日期: 2019-12-13 出版日期: 2020-10-10

基金资助:Supported by the Project of Shaanxi Provincial Science and Technology Department (2020JM602, 2019JM471), the Team of Syngas Catalytic Conversion of Shaanxi University of Technology, the Youth National Natural Science Foundation of China (No. 21373132, 21603133), the Key Project of Education Department of Shaanxi Province (18JS023) and the Project of Shaanxi University of technology (SLGQD2017-14)

通讯作者: jiufulu@163.com E-mail: jiufulu@163.com

引用本文:

季晓晖;赵娟;卢久富;葛红光. Synthesis, Crystal and Biological Activity of 3-(2,4-Difluorobenzyl)-5-(p-tolyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-amine[J]. 结构化学, 2020, 39(10): 1912-1917.
JI Xiao-Hui;ZHAO Juan;LU Jiu-Fu;GE Hong-Guang. Synthesis, Crystal and Biological Activity of 3-(2,4-Difluorobenzyl)-5-(p-tolyl)-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-amine. CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2020, 39(10): 1912-1917.

链接本文:

http://manu30.magtech.com.cn/jghx/CN/ 或 http://manu30.magtech.com.cn/jghx/CN/Y2020/V39/I10/1912

REFERENCES
(1) Kamel, M. M.; Megally Abdo, N. Y. Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents. Eur. J. Med. Chem. 2014, 86, 75–80.
(2) You, W. K.; Sennino, B.; Williamson, C. W.; Falcón, B.; Hashizume, H.; Yao, L. C.; Aftab, D. T.; McDonald, D. M. VEGF and c-met blockade amplify angiogenesis inhibition in pancreatic islet. Cancer Res. 2011, 71, 4758–768.
(3) Liu, J.; Hao, X. C.; Shi, D.; Ye, C.; Yang, W. Synthesis of novel 1-arylpyrazolo[3,4-b][1,5]benzodiazepine derivatives. Journal of Liaoning University (Natural Sciences Edition) 2018, 45, 244–248.
(4) Hoelder, S.; Clarke, P. A.; Workman, P. Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol. Oncol. 2012, 6, 155–176.
(5) Liu, X. H.; Zhai, Z. W.; Xu, X. Y.; Yang, M. Y.; Sun, Z. H.; Weng, J. Q.; Tan, C. X.; Chen, J. Facile and efficient synthesis and biological activity determination of novel 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one derivatives via microwave irradiation. Bioorg. Med. Chem. Lett. 2015, 25, 5524–5228.
(6) Shi, J. T.; Gong, Y. L.; Li, J.; Wang, Y.; Chen, Y.; Ding, S.; Liu, J. Synthesis, structure and biological activity of 2-[2-(4-fluorobenzylidene) hydrazinyl]-4-(1-methyl-1H-indol-3-yl)thieno[3,2-d] pyrimidine. Chinese J. Struct. Chem. 2019, 38, 1810–1816.
(7) Rivers, E. C.; Mancera, R. L. New anti-tuberculosis drugs in clinical trials with novel mechanisms of action. Drug Discov. Today 2008, 13, 1090–1098.
(8) Asghar, U.; Witkiewicz, A. K.; Turner, N. C.; Knudsen, E. S. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat. Rev. Drug Discov. 2015, 14, 130–146.
(9) Gouda, M. A.; Berghot, M. A.; Shoeib, A. I. Synthesis and antimicrobial of new anthraquinone derivatives incorporating pyrazole moiety. Eur. J. Med. Chem. 2010, 45, 1843–1848.
(10) Shaaban, M. R.; Saleh, T. S.; Mayhoub, A. S.; Mansour, A.; Farag, A. M. Synthesis and analgesic/anti-inflammatory evaluation of fused heterocyclic ring systems incorporating phenylsulfonyl moiety. Bioorg. Med. Chem. 2008, 16, 6344–6352.
(11) Auzzi, G.; Bruni, F.; Cecchi, L.; Costanzo, A.; Vettori, L. P.; Pirisino, R.; Corrias, M.; Ignesti, G.; Banchelli, G.; Raimondi, L. 2-Phenylpyrazolo[1,5-a]pyrimidin-7-ones. A new class of nonsteroidal antiinflammatory drugs devoid of ulcerogenic activity. J. Med. Chem. 1983, 26, 1706–1709.
(12) Li, Y.; Gao, W.; Li, F.; Wang, J.; Zhang, J.; Yang, Y.; Zhang, S.; Yang, L. An in silico exploration of the interaction mechanism of pyrazolo[1,5-a]pyrimidine type CDK2 inhibitors. Mol. Bio. Syst. 2013, 9, 2266–2281.
(13) Lu, J. F.; Jin, L. X.; Ge, H. G.; Ji, X. H.; Guo, X. H.; Tian, G. H.; Song, J.; Jiang, M. Synthesis, crystal, computational study and biological activity of N-(1-(2,4-dichlorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-4-(N,N-dipropylsulfamoyl)benzamide. Chinese J. Struct. Chem. 2017, 36, 1810–1816.
(14) Ji, X. H.; Zhao, J.; Lu, J. F.; Jin, L. X.; Ge, H. G. Synthesis, crystal structure and biological activity of 1-(3-amino-4-morpholino-1H-indazole- 1-carbonyl)-N-(4-fluorophenyl)cyclopropane-1-carboxamide. Chinese J. Struct. Chem. 2019, 38, 1889–1894.
(15) Lu, J. F.; Huang, P.; Zhang, D.; Wang, Q.; Zheng, N.; Wu, R.; Liu, Q.; Jin, L. X.; Yu, X. H.; Ji, X. H.; Gao, Y. H.; Ge, H. G. 1-(3-Amino-4- morpholino-1H-indazole-1-carbonyl)-N-phenylcyclopropane-1-carboxamide: Design, synthesis, crystal structure, antitumor activity, DFT and Hirshfeld surface analysis. J. Mol. Struct. 2020, 1210, 127996–127999.
(16) Sheldrick, G. M. SHELXS-97, Program for the Solution of Crystal Structures. University of Göttingen, Germany 1997.
(17) Sheldrick, G. M. SHELXL-2014/7, Crystal Structure Refinement with SHELXL. Acta Crystallographica C 2015, C71, 3-8.
(18) Bergerhoff, G.; Berndt, M.; Brandenburg, K. Evaluation of crystallographic data with the program DIAMOND. J. Res. Natl. Inst. Stand. Technol.
1996, 101, 221–225.