A<sub>2A</sub>腺苷受体拮抗剂中间体与抗结剂合成方法研究

doi:10.3785/j.issn.1008-9497.2016.04.008

浙江大学学报（理学版）

2016, Vol. 43

Issue (4): 420-425 DOI: 10.3785/j.issn.1008-9497.2016.04.008

化学

A_2A腺苷受体拮抗剂中间体与抗结剂合成方法研究

屠美玲¹, 俞卫平², 冯涛², 贾继宁¹, 张云¹, 张建庭¹

1. 浙江工业大学化学工程与材料学院, 浙江杭州 310014;
2. 杭州职业技术学院, 浙江杭州 310018

Synthesis of an important intermediate of antagonists of the human A_2A adenosine receptor

TU Meilin¹, YU Weiping², FENG Tao², JIA Jining¹, ZHANG Yun¹, ZHANG Jianting¹

1. Chemical Engineering and Material College, Zhejiang University of Technology, Hangzhou 310014, China;
2. Hangzhou Vocational and Technical College, Hangzhou 310018, China

全文: PDF(729 KB)

摘要： 基于官能化的三唑并［4，5-d］嘧啶类拮抗剂对人体内A_2A腺苷受体拮抗作用的干预治疗，能有效缓解帕金森综合征的临床症状.该类拮抗剂可以提高多巴胺神经元对纹状体多巴胺的敏感度.重点研究了三唑并［4，5-d］嘧啶类拮抗剂合成所需的重要中间体4-氯-1H-［1，2，3］三唑并［d］嘧啶-6-胺的合成、表征及应用.并对该中间体进行活性拼接，制备了含呋喃基的三唑并［4，5-d］嘧啶类拮抗剂8.

关键词： 帕金森综合征; A_2A腺苷受体拮抗剂; 合成

Abstract: Antagonism of the human A_2A receptor has been implicated as a point of therapeutic intervention in the alleviation of the symptoms associated with Parkinson's disease. That is to say, at least in part, this kind of antagonists can improve the sensitivity of the dopaminergic neurons to the residual, and deplete levels of striatal dopamine. Herein, we reported a novel synthesis strategy of an important intermediate (4-chloro-1H-benzo[d][1,2,3]triazol-6-amine) of antagonists of the human A_2A adenosine receptor. Additionally, we had also prepared the adenosine receptor 8.

Key words: Parkinson's disease antagonist of human A_2A adenosine receptor synthesis

收稿日期: 2015-04-07 出版日期: 2016-04-28

CLC:

TQ46

作者简介: 屠美玲(1982-),ORCID:http://orcid.org/0000-0002-8700-3524,女,硕士,实验师,主要从事有机中间体研究,E-mail:tu_ml@126.com.

	服务
	把本文推荐给朋友
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	屠美玲
	俞卫平
	冯涛
	贾继宁
	张云
	张建庭

引用本文:

屠美玲, 俞卫平, 冯涛, 贾继宁, 张云, 张建庭. A_2A腺苷受体拮抗剂中间体与抗结剂合成方法研究[J]. 浙江大学学报（理学版）, 2016, 43(4): 420-425.

TU Meilin, YU Weiping, FENG Tao, JIA Jining, ZHANG Yun, ZHANG Jianting. Synthesis of an important intermediate of antagonists of the human A_2A adenosine receptor. Journal of ZheJIang University(Science Edition), 2016, 43(4): 420-425.

链接本文:

https://www.zjujournals.com/sci/CN/10.3785/j.issn.1008-9497.2016.04.008 或 https://www.zjujournals.com/sci/CN/Y2016/V43/I4/420

[1] JANKOVIC J. Parkinson's disease: Clinical features and diagnosis[J]. J Neurol Neurosurg Psychiatry,2008,79(4):368-376.
[2] BOLLER F , MIZUTANI T , ROESSMANN U,et al. Parkinson disease, dementia, and alzheimer disease: Clinicopathological correlations[J]. Ann Neurol,1980,7(4):329-335.
[3] BLANDINI F, PORTER R H P, GREENAMYRE J T. Glutamate and Parkinson's disease[J].Mol Neurobiol,1996,12(1):73-94.
[4] COTZIAS G C, PAPAVASILIOU P S, GELLENE R. Modification of Parkinsonism-chronic treatment with L-dopa[J]. New Engl J Med,1969,280(7):337-345.
[5] BARBEAU.L-dopa therapy in Parkinson's disease: A critical review of nine years' experience[J]. Can Med Assoc J,1969,101(13):59-68.
[6] RINNE U K. Problems associated with long-term levodopa treatment of Parkinson's disease[J]. Acta Neurol Scand: Suppl,1983,95:19-26.
[7] 张丹,张建军,刘耕陶.治疗帕金森病新药:腺苷A_2A受体拮抗剂[J].中国药理学通报,2006,22(8):897-900. ZHANG Dan, ZHANG Jianjun, LIU Gengtao. A novel therapy for PD-adenosine A_2A receptor antagonist[J]. Chinese Pharmacological Bulletin,2006,22(8):897-900.
[8] SCHIFFMANN S N, HALLEUX P, MENU R, et al. Adenosine A_2A receptor expression in striatal neurons: Implications for basal ganglia pathophysiology[J]. Drug Dev Res,1993,28(3):381-385.
[9] SVENNINGSSONP, LE MOINE C, FISONE G, et al. Distribution, biochemistry and function of striatal adenosine A_2A receptors[J]. Prog Neurobiol,1999,59(4):355-396.
[10] 王恒会,罗蔚锋. 腺苷A_2A受体拮抗剂治疗帕金森病的研究进展[J].国外医学:老年医学分册,2006,27(6):244-247. WANG Henghui, LUO Weifeng. Progress adenosine A_2A receptor antagonist treatment of Parkinson's disease[J]. Foreign Medical Sciences:Geriatrics,2006,27(6):244-247.
[11] RABASSEDA X, SORBERA L A, MARTIN L , et al. Monographs-kw-6002. Antiparkinsonian, antidepressant, adenosine A₂ antagonist[J]. Drugs Future,2001,26(1):20-24.
[12] LEWITT P A, GUTTMAN M, TETRUD J W, et al. Adenosine A_2A receptor antagonist istradefylline (KW-6002) reduces "off" time in Parkinson's disease: A doubleblind, randomized, multicenter clinical trial (6002-US-005)[J]. Ann Neurol,2008,63(3):295-302.
[13] HOCKEMEYER J, BURBIEL J C , MUELLER C E. Multigram-scale syntheses, stability, and photoreactions of A_2A adenosine receptor antagonists with 8-styrylxanthine structure: Potential drugs for Parkinson's disease[J]. J Org Chem,2004,69(10):3308-3318.

[1]	潘峰, 王磊, 郭怡, 沈金滢, 潘晓峰, 郑卫新. 2-碘-3-（对甲苯磺酰氧基）苯基醚的选择性合成[J]. 浙江大学学报（理学版）, 2021, 48(5): 579-583.
[2]	裘佳萍, 杜培臻, 雷鸣, 田梅, 方群, 张宏, 徐光明, 潘建章. 微型模块化微流控PET显像剂合成仪的研制及应用[J]. 浙江大学学报（理学版）, 2021, 48(5): 573-578.
[3]	沈杭锋, 崔洁, 刘敏, 方桃妮, 陈光宇. 福建登陆北上台风对杭州影响的对比分析[J]. 浙江大学学报（理学版）, 2020, 47(5): 582-593.
[4]	高百俊, 张佳, 朱振扬. 弱M-可补子群对合成因子的影响[J]. 浙江大学学报（理学版）, 2019, 46(5): 526-528.
[5]	李佳慧, 杨芳芳, 王珍, 张赛南, 王首锋. 新型双功能谷胱甘肽合成酶的真核和原核表达[J]. 浙江大学学报（理学版）, 2019, 46(4): 474-481.
[6]	江银枝, 程本能, 孙红英, 时永强. Salen双核Cu²⁺配合物的合成及催化染料降解[J]. 浙江大学学报（理学版）, 2016, 43(6): 733-739.
[7]	桂彦, 王培玉, 李峰, 刘杨. 基于GPU加速的几何纹理合成方法[J]. 浙江大学学报（理学版）, 2016, 43(6): 638-646.
[8]	汪冒君，宣南霞，吴军. 乙酰乳酸合成酶与抑制剂ZJ0777及CIE的分子对接和分子动力学模拟[J]. 浙江大学学报（理学版）, 2015, 42(6): 709-713.
[9]	黄志真,黄　宪. 钯催化芳卤与亚磷酸二烷酯的相转移偶联反应[J]. 浙江大学学报（理学版）, 1998, 25(3): 59-61.
[10]	梅明华,楼　辉. 中孔分子筛MCM-41 的合成与表征[J]. 浙江大学学报（理学版）, 1998, 25(2): 62-65.
[11]	林秋月;龚枉秋. 三元混配合物中的芳环堆积作用研究‘N . Zn2十一Phen-PCA体系的萃取研究和混配合物的合成及表征[J]. 浙江大学学报（理学版）, 1997, 24(3): 234-238.
[12]	龚钮秋；沈良. 把与苯基梭酸和1,2一二(二苯膦）乙烷混配合物的合成与表征[J]. 浙江大学学报（理学版）, 1996, 23(2): 177-181.

Viewed

Full text

Abstract

Cited

Shared

Discussed