腺苷A2B受体上腺苷类似物的功能筛选：寻找强效激动剂。
A functional screening of adenosine analogues at the adenosine A2B receptor: a search for potent agonists.
作者信息
de Zwart M, Link R, von Frijtag Drabbe Künzel J K, Cristalli G, Jacobson K A, Townsend-Nicholson A, IJzerman A P
机构信息
Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, Leiden University, The Netherlands.
出版信息
Nucleosides Nucleotides. 1998 Jun;17(6):969-85. doi: 10.1080/07328319808004215.
Abstract
Various adenosine analogues were tested at the adenosine A2B receptor. Agonist potencies were determined by measuring the cyclic AMP production in Chinese Hamster Ovary cells expressing human A2B receptors. 5'-N-Substituted carboxamidoadenosines were most potent. 5'-N-Ethylcarboxamidoadenosine (NECA) was most active with an EC50 value of 3.1 microM. Other ribose modified derivatives displayed low to negligible activity. Potency was reduced by substitution on the exocyclic amino function (N6) of the purine ring system. The most active N6-substituted derivative N6-methyl-NECA was 5 fold less potent than NECA. C8- and most C2-substituted analogues were virtually inactive. 1-Deaza-analogues had a reduced potency, 3- and 7-deazaanalogues were not active.
摘要
在腺苷A2B受体上测试了多种腺苷类似物。通过测量表达人A2B受体的中国仓鼠卵巢细胞中的环磷酸腺苷生成来确定激动剂效力。5'-N-取代的羧酰胺基腺苷效力最强。5'-N-乙基羧酰胺基腺苷（NECA）活性最高，EC50值为3.1微摩尔。其他核糖修饰的衍生物活性低至可忽略不计。嘌呤环系统的环外氨基功能（N6）上的取代会降低效力。活性最高的N6-取代衍生物N6-甲基-NECA的效力比NECA低5倍。C8-和大多数C2-取代的类似物实际上没有活性。1-脱氮类似物效力降低，3-和7-脱氮类似物没有活性。
相似文献
1
A functional screening of adenosine analogues at the adenosine A2B receptor: a search for potent agonists.腺苷A2B受体上腺苷类似物的功能筛选：寻找强效激动剂。
Nucleosides Nucleotides. 1998 Jun;17(6):969-85. doi: 10.1080/07328319808004215.
2
A2B adenosine receptor agonists: synthesis and biological evaluation of 2-phenylhydroxypropynyl adenosine and NECA derivatives.A2B 腺苷受体激动剂：2-苯基羟基丙炔基腺苷和 NECA 衍生物的合成与生物学评价
Nucleosides Nucleotides Nucleic Acids. 2004;23(1-2):471-81. doi: 10.1081/ncn-120028340.
3
Comparative pharmacology of human adenosine receptor subtypes - characterization of stably transfected receptors in CHO cells.人腺苷受体亚型的比较药理学——CHO细胞中稳定转染受体的特性研究
Naunyn Schmiedebergs Arch Pharmacol. 1998 Jan;357(1):1-9. doi: 10.1007/pl00005131.
4
Characterization of the human brain putative A2B adenosine receptor expressed in Chinese hamster ovary (CHO.A2B4) cells.在中国仓鼠卵巢（CHO.A2B4）细胞中表达的人脑海马区假定A2B腺苷受体的特性分析
Br J Pharmacol. 1996 Nov;119(6):1286-90. doi: 10.1111/j.1476-5381.1996.tb16035.x.
5
Pharmacological characterization of adenosine A2B receptors: studies in human mast cells co-expressing A2A and A2B adenosine receptor subtypes.腺苷A2B受体的药理学特性：在共表达A2A和A2B腺苷受体亚型的人肥大细胞中的研究
Biochem Pharmacol. 1998 Mar 1;55(5):627-33. doi: 10.1016/s0006-2952(97)00512-1.
6
An endogenous A2B adenosine receptor coupled to cyclic AMP generation in human embryonic kidney (HEK 293) cells.一种内源性A2B腺苷受体，与人类胚胎肾（HEK 293）细胞中环磷酸腺苷的生成相关联。
Br J Pharmacol. 1997 Oct;122(3):546-50. doi: 10.1038/sj.bjp.0701401.
7
Differences in the order of potency for agonists but not antagonists at human and rat adenosine A2A receptors.人类和大鼠腺苷A2A受体上激动剂的效价顺序存在差异，但拮抗剂的效价顺序无差异。
Biochem Pharmacol. 1999 Jan 1;57(1):65-75. doi: 10.1016/s0006-2952(98)00298-6.
8
Synthesis and biological activity of a new series of N6-arylcarbamoyl, 2-(Ar)alkynyl-N6-arylcarbamoyl, and N6-carboxamido derivatives of adenosine-5'-N-ethyluronamide as A1 and A3 adenosine receptor agonists.作为A1和A3腺苷受体激动剂的一系列新型N6-芳基氨基甲酰基、2-（芳基）炔基-N6-芳基氨基甲酰基和腺苷-5'-N-乙基脲酰胺的N6-羧酰胺衍生物的合成及生物活性
J Med Chem. 1998 Aug 13;41(17):3174-85. doi: 10.1021/jm980147p.
9
Relative agonist potencies of C2-substituted analogues of adenosine: evidence for adenosine A2B receptors in the guinea pig aorta.腺苷C2-取代类似物的相对激动剂效力：豚鼠主动脉中腺苷A2B受体的证据。
Eur J Pharmacol. 1992 Jun 5;216(2):235-42. doi: 10.1016/0014-2999(92)90365-b.
10
Adenosine A2B-receptor-mediated cyclic AMP accumulation in primary rat astrocytes.腺苷A2B受体介导的原代大鼠星形胶质细胞中环磷酸腺苷的积累。
Br J Pharmacol. 1994 Jan;111(1):191-8. doi: 10.1111/j.1476-5381.1994.tb14043.x.
引用本文的文献
1
1,3-Dialkylxanthine Derivatives Having High Potency as Antagonists at Human A Adenosine Receptors.作为人 A 型腺苷受体拮抗剂具有高效能的 1,3 - 二烷基黄嘌呤衍生物。
Drug Dev Res. 1999 May;47(1):45-53. doi: 10.1002/(sici)1098-2299(199905)47:1<45::aid-ddr6>3.0.co;2-u.
2
Kinetic profiling and functional characterization of 8-phenylxanthine derivatives as A adenosine receptor antagonists.作为 A 腺苷受体拮抗剂的 8-苯基黄嘌呤衍生物的动力学分析和功能特征。
Biochem Pharmacol. 2022 Jun;200:115027. doi: 10.1016/j.bcp.2022.115027. Epub 2022 Apr 6.
3
A Adenosine Receptors: Protective vs. Damaging Effects Identified Using Novel Agonists and Antagonists.A 腺苷受体：使用新型激动剂和拮抗剂确定的保护作用与损伤作用
Drug Dev Res. 1998 Nov-Dec;45(3-4):113-124. doi: 10.1002/(SICI)1098-2299(199811/12)45:3/4<113::AID-DDR5>3.0.CO;2-S. Epub 1999 Mar 1.
4
Blood Platelet Adenosine Receptors as Potential Targets for Anti-Platelet Therapy.血小板腺苷受体作为抗血小板治疗的潜在靶点。
Int J Mol Sci. 2019 Nov 3;20(21):5475. doi: 10.3390/ijms20215475.
5
The role of mechanical forces and adenosine in the regulation of intestinal enterochromaffin cell serotonin secretion.机械力和腺苷在调节肠道嗜铬细胞 5-羟色胺分泌中的作用。
Am J Physiol Gastrointest Liver Physiol. 2012 Feb 1;302(3):G397-405. doi: 10.1152/ajpgi.00087.2011. Epub 2011 Oct 28.
6
Multivalent dendrimeric and monomeric adenosine agonists attenuate cell death in HL-1 mouse cardiomyocytes expressing the A(3) receptor.多价树状和单体腺苷激动剂可减轻表达 A(3)受体的 HL-1 小鼠心肌细胞的细胞死亡。
Biochem Pharmacol. 2010 Jul 15;80(2):188-96. doi: 10.1016/j.bcp.2010.03.020. Epub 2010 Mar 25.
7
AMP579 is revealed to be a potent A2b-adenosine receptor agonist in human 293 cells and rabbit hearts.AMP579 被证实在人 293 细胞和兔心中是一种有效的 A2b- 腺苷受体激动剂。
Basic Res Cardiol. 2010 Jan;105(1):129-37. doi: 10.1007/s00395-009-0056-9.
8
Recent improvements in the development of A(2B) adenosine receptor agonists.近年来，A(2B) 腺苷受体激动剂的开发取得了进展。
Purinergic Signal. 2009 Mar;5(1):3-19. doi: 10.1007/s11302-009-9140-8. Epub 2009 Jan 31.
9
Recent improvements in the development of A(2B) adenosine receptor agonists.近年来，A(2B) 腺苷受体激动剂的研发取得了进展。
Purinergic Signal. 2008 Dec;4(4):287-303. doi: 10.1007/s11302-008-9097-z. Epub 2008 Apr 29.
10
Probing distal regions of the A2B adenosine receptor by quantitative structure-activity relationship modeling of known and novel agonists.通过已知和新型激动剂的定量构效关系建模探究A2B腺苷受体的远端区域
J Med Chem. 2008 Apr 10;51(7):2088-99. doi: 10.1021/jm701442d. Epub 2008 Mar 6.
本文引用的文献
1
2
Characterization of the human brain putative A2B adenosine receptor expressed in Chinese hamster ovary (CHO.A2B4) cells.在中国仓鼠卵巢（CHO.A2B4）细胞中表达的人脑海马区假定A2B腺苷受体的特性分析
Br J Pharmacol. 1996 Nov;119(6):1286-90. doi: 10.1111/j.1476-5381.1996.tb16035.x.
3
N6,C8-distributed adenosine derivatives as partial agonists for adenosine A1 receptors.作为腺苷A1受体部分激动剂的N6，C8分布的腺苷衍生物
J Med Chem. 1996 Mar 29;39(7):1463-71. doi: 10.1021/jm950267m.
4
Inhibition of human monocyte TNF production by adenosine receptor agonists.
Life Sci. 1993;52(24):1917-24. doi: 10.1016/0024-3205(93)90632-d.
5
Functional characterization of three adenosine receptor types.三种腺苷受体类型的功能特性
Br J Pharmacol. 1993 Jul;109(3):693-8. doi: 10.1111/j.1476-5381.1993.tb13629.x.
6
Functional coupling of human adenosine receptors to a ligand-dependent reporter gene system.人类腺苷受体与配体依赖性报告基因系统的功能偶联。
Biochem Biophys Res Commun. 1994 Jan 28;198(2):626-31. doi: 10.1006/bbrc.1994.1091.
7
Molecular cloning and characterization of the human A3 adenosine receptor.人类A3腺苷受体的分子克隆与特性分析
Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10365-9. doi: 10.1073/pnas.90.21.10365.
8
Functional characterization of the A2b adenosine receptor in NIH 3T3 fibroblasts.NIH 3T3成纤维细胞中A2b腺苷受体的功能特性
Biochem Pharmacol. 1994 Mar 2;47(5):801-14. doi: 10.1016/0006-2952(94)90480-4.
9
Structure-activity relationships of N6-benzyladenosine-5'-uronamides as A3-selective adenosine agonists.N6-苄基腺苷-5'-脲酰胺作为A3选择性腺苷激动剂的构效关系
J Med Chem. 1994 Mar 4;37(5):636-46. doi: 10.1021/jm00031a014.
10
2-Substitution of N6-benzyladenosine-5'-uronamides enhances selectivity for A3 adenosine receptors.N6-苄基腺苷-5'-脲酰胺的2-取代增强了对A3腺苷受体的选择性。
J Med Chem. 1994 Oct 14;37(21):3614-21. doi: 10.1021/jm00047a018.
Zotero 插件