2-chloro-2',3'-O-(ethoxymethylidene) adenosine | 56720-43-5

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2-chloro-2',3'-O-(ethoxymethylidene) adenosine
• 英文别名: [(3aR,4R,6R,6aR)-4-(6-amino-2-chloropurin-9-yl)-2-ethoxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol
• CAS: 56720-43-5
• 化学式: C₁₃H₁₆ClN₅O₅
• 分子量: 357.754
• InChiKey: XNCOVLJPSFRZDT-QHQIBUKQSA-N

物化性质

• 沸点：
  588.4±60.0 °C(Predicted)
• 密度：
  1.97±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-chloro-2',3'-O-(ethoxymethylidene) adenosine 在 正丁基锂 、 甲酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 2.25h， 生成 2-[2-(4-氯苯基)乙氧基]腺苷
  参考文献：
  名称：

  2-Aralkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor

  摘要：

  A Langendorff guinea pig heart preparation served for the assay of agonist potency of a series of 26 2-aralkoxyadenosines at the A1 and A2 receptors of, respectively, the atrioventricular node (conduction block) and coronary arteries (vasodilation). All of the analogues are weak agonists at the A1 receptor, requiring concentrations > 9-mu-M to cause second degree heart block. At the A2 receptor 2-phenethoxyadenosine is the most potent of the 2-phenylalkyladenosines. The activity of ring-substituted (F, Cl, CH3, and OCH3) 2-phenethoxyadenosines increases ortho < meta < para. The EC50s of coronary vasoactivity of several para-substituted analogues are in the subnanomolar range. The most potent analogue, 2-[2-(4-methylphenyl)ethoxy]adenosine 19, has an EC50 for coronary vasodilation of 190 pM and an A1/A2 selectivity ratio of 44000. Aryl groups such as thienyl, indoloyl, or naphthyl also support A2 agonist activity. Although 2-oxoadenosine is 3 times more vasoactive than 2-aminoadenosine, the activities of the phenyl derivatives are markedly different; 2-phenoxyadenosine is 23 times weaker than 2-(phenylamino)adenosine (CV-1808).

  DOI：

  10.1021/jm00108a015

文献信息

• Synthesis of 2-aralkoxyadenosines and 2-alkoxyadenosines
  申请人：——

  公开号：US20030199686A1

  公开（公告）日：2003-10-23

  The invention provides new methods for synthesis of 2-aralkyloxyadenosines and 2-alkoxyadenosines. The invention is particularly useful for synthesis of 2-[2-(4-chlorophenyl)ethoxy]adenosine. Preferred methods of the invention include activating a guanosine compound followed by hydrolysis; alkylating the hydrolyzed compound with subsequent animation to provide a 2-aralkyloxyadenosine or a 2-alkoxyadenosine compound.

  这项发明提供了合成2-芳基氧基腺苷和2-烷氧基腺苷的新方法。该发明特别适用于合成2-[2-(4-氯苯基)乙氧基]腺苷。该发明的首选方法包括激活鸟苷化合物，然后进行水解；烷基化水解后的化合物，随后进行胺化，以提供2-芳基氧基腺苷或2-烷氧基腺苷化合物。
• Synthesis of 2-aralkyloxyadenosines, 2-alkoxyadenosines, and their analogs
  申请人：Moorman R. Allan

  公开号：US20060135466A1

  公开（公告）日：2006-06-22

  Provided is a method for the synthesis of an aralkyloxyadenosine or an alkoxyadenosine. The method includes protecting the hydroxyl sugar groups with a protecting group to produce a protected halogenated adenosine. The protected halogenated adenosine is alkoxylated, and the hydroxyl sugar groups of the protected halogenated adenosine are deprotected to provide the aralkyloxyadenosine or alkoxyadenosine.

  提供了一种合成芳基氧基腺苷或烷氧基腺苷的方法。该方法包括将糖基上的羟基保护起来以产生受保护的卤代腺苷。受保护的卤代腺苷被烷氧化，然后去除受保护的卤代腺苷的糖基上的羟基保护基，从而得到芳基氧基腺苷或烷氧基腺苷。
• 2-Alkoxyadenosines: potent and selective agonists at the coronary artery A2 adenosine receptor
  作者：Masayuki Ueeda、Robert D. Thompson、Luis H. Arroyo、Ray A. Olsson

  DOI：10.1021/jm00108a014

  日期：1991.4

  A Langendorff guinea pig heart preparation served for the assay of agonist activity of a series of 24 2-alkoxyadenosines at the A1 and A2 adenosine receptors of, respectively, the atrioventricular node (conduction block) and coronary arteries (vasodilation). Activities are low at the A1 receptor and do not show a clear relationship to the size or hydrophobicity of the C-2 substituent. All the analogues are more potent at the A2 receptor, activity varying directly with the size and hydrophobicity of the alkyl group. The most potent analogue in this series, 2-(2-cyclohexylethoxy)adenosine, has an EC50 of 1 nM for coronary vasodilation and is 8700-fold selective for the A2 receptor.
• 2-Substituted adenosine derivatives: affinity and efficacy at four subtypes of human adenosine receptors
  作者：Zhan-Guo Gao、Liaman K. Mamedova、Peiran Chen、Kenneth A. Jacobson

  DOI：10.1016/j.bcp.2004.06.011

  日期：2004.11

  The affinity and efficacy at four subtypes (A(1), A(2A), A(2B) and A(3)) of human adenosine receptors (ARs) of a wide range of 2-substituted adenosine derivatives were evaluated using radioligand binding assays and a cyclic AMP functional assay in intact CHO cells stably expressing these receptors. Similar to previous studies of the N-6-position, several 2-substituents were found to be critical structural determinants for the A(3)AR activation. The following adenosine 2-ethers were moderately potent partial agonists (K-i, nM): benzyl (117), 3-chlorobenzyl (72), 2-(3-chlorophenyl)ethyl (41), and 2-(2-naphthyl)ethyl (130). The following adenosine 2-ethers were A(3)AR antagonists: 2,2-diphenylethyl, 2-(2-norbornan)ethyl, R- and S-2-phenylbutyl, and 2-(2-chlorophenyl)ethyl. 2-(S-2-Phenylbutyloxy)adenosine as an A(3)AR antagonist right-shifted the concentration-response curve for the inhibition by NECA of cyclic AMP accumulation with a K-B value of 212 nM, which is similar to its binding affinity (K-i = 175 nM). These 2-substituted adenosine derivatives were generally less potent at the A(1)AR in comparison to the A(3)AR, but fully efficacious, with binding K-i values over 100 nM. The 2-phenylethyl moiety resulted in higher A(3)AR affinity (K-i in nM) when linked to the 2-position of adenosine through an ether group (54), than when linked through an amine (310) or thioether (1960). 2-[2-(1-Naphthyl)ethyloxyladenosine (K-i = 3.8 nM) was found to be the most potent and selective (>50-fold) A(2A) agonist in this series. Mixed A(2A)/A(3)AR agonists have been identified. Interestingly, although most of these compounds were extremely weak at the A(2B)AR, 2-[2-(2-naphthyl)ethyloxyladenosine (EC50 = 1.4 muM) and 2-[2-(2-thienyl)-ethyloxy]adenosine (EC50 = 1.8 (M) were found to be relatively potent A(2B) agonists, although less potent than NECA (EC50 = 140 nM). (C) 2004 Elsevier Inc. All rights reserved.
• UEEDA, MASAYUKI;THOMPSON, ROBERT D.;ARROYO, LUIS H.;OLSSON, RAY A., J. MED. CHEM., 34,(1991) N, C. 1334-1339
  作者：UEEDA, MASAYUKI、THOMPSON, ROBERT D.、ARROYO, LUIS H.、OLSSON, RAY A.

  DOI：——

  日期：——