新环6-甲基咪唑[1,2-d]并-1,2,3,4-噻三唑-5-羧酸衍生物的合成
Synthesis of Neoring 6-Methylimidazo[1,2-d][1,2,3,4]thiatriazole-5-carboxylic Acid Derivatives
摘要:

目的：为了寻找抑制细胞分裂周期磷酸酯酶CDC25B的抗肿瘤新药，设计和合成6-甲基-咪唑[1,2-d]并-1,2,3,4-噻三唑-5-羧酸衍生物是有意义的。方法：以5-氨基-1,2,3,4-噻三唑和溴代乙酰乙酸乙酯为原料，经过关环，肼解，缩合等反应合成目标化合物。结果：合成了5种新的化合物。结论：所得化合物，通过元素分析、IR、1H NMR和质谱分析确定了其结构，并且化合物3和4a对CDC25B的抑制率(%抑制率)分别为85.4和82.3，具有一定的生物活性。 Objective: In order to search the new anti-cancer drugs inhibiting with cell division cycle CDC25B phosphatase, designing and synthesizing 6-Methylimidazo[1,2-d][1,2,3,4]thiatriazole-5-carboxylic acid derivatives is meaningful. Methods: The objective compounds were synthesized by cyclization, hydrazinolysis, condensation in the basis of 5-amino-1,2,3,4-triazole and bromine ethyl acetoacetate. Result: The five new kinds of compounds were synthesized. Conclusion: The structures of the compounds were determined by elemental analysis, IR, 1H NMR and MS, furthermore, it was found that the inhibition rates (% inhibition) of the CDC25B were 85.4 and 82.3 by compounds 3 and 4a with a certain biological activity.

文章引用：钞智锋, 布仁, 鲁源. 新环6-甲基咪唑[1,2-d]并-1,2,3,4-噻三唑-5-羧酸衍生物的合成[J]. 药物化学, 2013, 1(1): 1-4. http://dx.doi.org/10.12677/HJMCE.2013.11001

参考文献

[1] H. Miyata, Y. Doki, H. Yamamoto, et al. Overexpression of CDC25B overrides radiation-induced G2-M arrest and results in increased apoptosis in esophageal cancer cells. Cancer Research, 2001, 61(7): 3188-3193.
[2] I. Takamasa, H. Yamamoto, M. Sekimoto, et al. Overexpression of CDC25B phosphatase as a novel marker of poor prognosis of human colorectal carcinoma. Cancer Research, 2000, 60(11): 3043-3050.
[3] 成静, 付强, 伍钢. CDC25B与恶性肿瘤研究进展[J]. 中华肿瘤防治杂志, 2007, 14(11): 872-875.
[4] 刘慧冰, 史惠蓉, 张瑞涛等. 卵巢癌组织中CDK1和CDC25B的表达[J]. 郑州大学学报(医学版), 2009, 44(2): 312-315.
[5] A. Andreani, M. Rambaldi, F. Andreani, et al. Potential anti- tumor agents XVI. Imidazo[2,1-b]thiazoles Agents potentiels anti-tumoraux XVI. Imidazo[2,1-b]thiazoles. European Journal of Medicinal Chemistry, 1988, 23: 385-389.
[6] A. Andreani, M. Rambaldi, A. Leoni, et al. Potential Antitumor Agents. Synthesis and Pharmacological Behavior of Imidazo[2, 1-b]thiazole Guanylhydrazones Bearing at Least One Chlorine. Journal of Medicinal Chemistry, 1996, 39(14): 2852-2855.
[7] H.-W. Yoo, M.-E. Suh and S. W. Park. Synthesis and Cytoto- xicity of 2-Methyl-4,9-dihydro-1-substituted-1H-imidazo[4,5-g] quinoxaline-4,9-diones and 2,3-Disubstituted-5,10-pyrazino[2,3-g] quinoxalinediones. Journal of Medicinal Chemistry, 1998, 41 (24): 4716-4722.
[8] A. Andreani, A. Granaiola, A. Leoni, et al. Synthesis and antitumor activity of substituted 3-(5-imidazo[2,1-b]thiazolyl- methylene)-2-indolinones. Anti-Cancer Drug Design, 2001, 16: 167-174.
[9] N. Terzioglu, A. Gürsoy. Synthesis and anticancer evaluation of some new hydrazone derivatives of 2,6-dimethylimidazo[2,1-b] [1,3,4]thiadiazole-5-carbohydRazide. European Journal of Medi- cinal Chemistry, 2003, 38(7-8): 781-786.
[10] 鲁源, 杨慧, 布仁等. 2-羟基-3-苯偶氮吡唑[5,1-c]苯并-1,2,4-三嗪衍生物的合成[J]. 化学试剂, 2004, 26(4): 239-240.
[11] 鲁源, 马庄. 3-羟基-5H-5-取代苯基吡唑[3,4-e]并-1,2,3,4-四嗪衍生物的合成[J]. 化学试剂, 2005, 27(11): 687-688.
[12] 鲁源, 陈朝军, 蔡孟深等. 3-羟基-7-氧代-5,6-二氢吡唑[3,4-e]并-1,2,4-三嗪的合成[J]. 化学试剂, 2006, 28(1): 41-42.
[13] 鲁源, 陈朝军, 蔡孟深等. 7-甲基-3-羟基吡唑[4,3-e]并-1,3,4-噁二嗪的合成[J]. 化学试剂, 2006, 28(4): 235-236.
[14] 杨波, 鲁源, 陈朝军等. 1-苯基-3-羟基-5-氧代-4-芳基偶氮吡唑衍生物的绿色合成[J]. 化学试剂, 2008, 30(4): 299-300.
[15] B. Yang, Y. Lu, C.-J. Chen, et al. The synthesis of 5-amino- 4-arylazo-3-methyl-1H-pyrazoles and 5-aryl-3-methyl-pyrazole [3,4-e][1,2,3,4]tetrazines. Dyes and Pigments, 2009, 83(2): 144- 147.
[16] J.-B. Liu, Y. Lu, C.-J. Chen, et al. Synthesis of some novel arylazo disperse dyes derived from 5-amino-tetrazolo[1,5-a] pyrimidin-7-ol as coupling component and investigation of their absorption spectra. Journal of Heterocyclic Chemistry, Accepted 23 December 2010, 2013 in press.
[17] 杨娜, 郝琳, 鲁源等. 5-亚氨基-7-氧代-6-芳基偶氮-1,3,4-噻二唑[3,2-a]并嘧啶衍生物的绿色合成[J]. 化学试剂, 2012, 34(12): 1139-1141.
[18] 成学丽, 钞智锋, 鲁源等. 7-甲基-3-巯基吡唑[4,3-e]并-1,3,4-噁二嗪衍生物的合成[J]. 化学试剂, 2013, 35(1): 77-79.
[19] 宋振丽, 郝琳, 鲁源等. 3-氨基-5H-5-芳基吡唑[3,4-e]并-1,2,3,4-四嗪衍生物的合成[J]. 化学试剂, 2013, 35(2): 176-177, 182.
[20] E. Lieber, E. Oftedahl, C. Pillai, et al. Notes—Infrared spectrum of the so-called 5-amino-1,2,3,4-thiatriazole. Journal of Organic Chemistry, 1957, 22 (4): 441-442.
[21] 关润伶, 朱红. 2-氨基-4-甲基-5-甲酰乙氧基噻唑氢溴酸盐的合成[J]. 北京交通大学学报, 2006, 30(3): 40-42.