2',3'-O-异亚丙基肌苷-5'-甲酸 | 28440-13-3

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 2',3'-O-异亚丙基肌苷-5'-甲酸
• 英文名称: 2',3'-O-isopropylideneinosine-5'-carboxylic acid
• 英文别名: 2',3'-O-isopropylideneinosine-5'-uronic acid；2',3'-isopropylidene-5'-oxoinosine；2',3'-O-isopropyridene-5'-oxoinosine；(3aS,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid；O²,O³-isopropylidene-1-(6-oxo-1,6-dihydro-purin-9-yl)-β-D-1-deoxy-ribofuranuronic acid；2',3'-isopropylideneinosine-5-carboxylic acid；2',3'-O-Isopropylideninosin-5'-carbonsaeure；(3aS,4S,6R,6aR)-6-(6-Hydroxy-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid；(3aR,4R,6S,6aS)-2,2-dimethyl-4-(6-oxo-1H-purin-9-yl)-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxole-6-carboxylic acid
• CAS: 28440-13-3
• 化学式: C₁₃H₁₄N₄O₆
• 分子量: 322.277
• InChiKey: KXUWTYIOZAXEOH-MCHASIABSA-N

物化性质

• 熔点：
  224-229 °C(Solv: acetone (67-64-1); ethyl ether (60-29-7))
• 沸点：
  669.3±65.0 °C(Predicted)
• 密度：
  1.92

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2',3'-O-异亚丙基肌苷-5'-甲酸 在 溶剂黄146 作用下， 以 水 为溶剂， 生成 1-deoxy-1-(1,6-dihydro-6-oxo-9H-purin-9-yl)-β-D-ribofuranuronic acid
  参考文献：
  名称：

  四氧化钌：氧化2'，3'-O-异亚丙基嘌呤核苷的温和试剂

  摘要：

  2'，3'-O-异亚丙基嘌呤核苷已被四氧化钌氧化，在中性条件下以定量收率提供了相应的5'-羧酸。

  DOI：

  10.1016/s0040-4039(00)74197-9
• 作为产物：
  描述：

  2',3'-isopropylideneadenosine-5'-carboxylic acid 在 adenylate deaminase EC 3.5.4.6 作用下， 以 phosphate buffer 、 二甲基亚砜 为溶剂， 生成 2',3'-O-异亚丙基肌苷-5'-甲酸
  参考文献：
  名称：

  腺苷脱氨酶（ADA）和腺苷酸脱氨酶（AMPDA）催化的2'，3'-O-异亚丙基腺苷-5'-羧酸的脱氨反应：底物电离对酶活性的影响

  摘要：

  腺苷脱氨酶（ADA）和腺苷酸脱氨酶（AMPDA）催化2'，3'-O-异丙基亚氨腺苷-5'-羧酸脱氨成相应的肌苷衍生物以及酶促反应速率对底物电离度的依赖性已经在不同的pH值下进行了研究。

  DOI：

  10.1080/15257770601052356

文献信息

• A Structure–Activity Relationship Study of Bitopic <i>N</i>⁶-Substituted Adenosine Derivatives as Biased Adenosine A₁ Receptor Agonists
  作者：Luigi Aurelio、Jo-Anne Baltos、Leigh Ford、Anh T. N. Nguyen、Manuela Jörg、Shane M. Devine、Celine Valant、Paul J. White、Arthur Christopoulos、Lauren T. May、Peter J. Scammells

  DOI：10.1021/acs.jmedchem.8b00047

  日期：2018.3.8

  prototypical A1AR agonists has been hindered due to dose limiting adverse effects. Recently, we demonstrated that the biased bitopic agonist 1, consisting of an adenosine pharmacophore linked to an allosteric moiety, could stimulate cardioprotective A1AR signaling in the absence of unwanted bradycardia. Therefore, this study aimed to investigate the structure–activity relationship of compound 1 biased

  腺苷A 1受体（A 1 AR）是心肌缺血再灌注损伤的潜在新型治疗靶标。但是，迄今为止，由于剂量限制的不良反应，原型A 1 AR激动剂的临床翻译受到了阻碍。最近，我们证明，由连接至变构部分的腺苷药效基团组成的偏向性双位激动剂1可以在不存在心动过缓的情况下刺激心脏保护性A 1 AR信号传导。因此，本研究旨在研究化合物1激动剂的构效关系。一系列的新的衍生物的1合成并进行药理学分析。对正构腺苷药效团，接头和变构2-氨基-3-苯甲酰基噻吩药效团进行了修饰，以探究其结构-活性关系，特别是在信号偏向方面以及A 1 AR活性和亚型选择性方面。总的来说，我们的发现表明，变构部分，特别是噻吩支架的4-（三氟甲基）苯基取代基，在赋予A 1 AR上的双位配体偏倚方面很重要。
• Drawing with Iron on a Gel Containing a Supramolecular Siderophore
  作者：Songjun Xiao、Paul J. Paukstelis、Richard D. Ash、Peter Y. Zavalij、Jeffery T. Davis

  DOI：10.1002/anie.201910872

  日期：2019.12.16

  5'-hydroxamic acid (HA) unit is pH-responsive and also chelates Fe3+ . When gels are prepared under basic conditions, the 5'-HA groups are deprotonated and the anionic hydrogel binds cationic thiazole orange (TO), signaled by enhanced fluorescence. The HA nucleoside 3, when immobilized in the G-quartet gel, acts as a supramolecular siderophore to form red complexes with Fe3+ . We patterned the hydrogel's surface

  与鸟苷（1）和KCl混合时，鸟苷5'-异羟肟酸（3）形成水凝胶。5'-异羟肟酸（HA）单元具有pH响应能力，并且还螯合了Fe3 +。当在碱性条件下制备凝胶时，5'-HA基团会去质子化，并且阴离子水凝胶会结合阳离子噻唑橙（TO），并发出增强的荧光信号。当HA核苷3固定在G四方凝胶中时，它充当超分子铁载体，与Fe3 +形成红色络合物。我们通过手工和使用3D打印机用FeCl3对水凝胶的表面进行了图案化。图案立即形成，肉眼可见，可用维生素C消除。这种水凝胶结合了自组装的G四重奏和铁氧体Fe3 +图案，强度高，可以模制成不同的形状，并且可以在工作台上稳定使用。在盐水下。
• N6-Substituted N-alkyladenosine-5'-uronamides: bifunctional ligands having recognition groups for A1 and A2 adenosine receptors
  作者：R. A. Olsson、Shozo Kusachi、Robert D. Thompson、Dieter Ukena、William Padgett、John W. Daly

  DOI：10.1021/jm00159a020

  日期：1986.9

  The coronary vasoactivity of N-ethyl-1'-deoxy-1'-(6-amino-9H-purin-9-yl)-beta-D-ribofuranuronamide (NECA, 1) is over 2 orders of magnitude greater than that of adenosine, and the vasoactivity of certain N6-substituted adenosines is as much as 1 order of magnitude greater. Such results suggest that a combination of appropriate modifications at N6 and C-5' might additively augment the agonist potency of adenosine. At low temperatures 1-deoxy-1-(6-chloro-9H-purin-9-yl)-2',3'-O-isopropylidene- beta-D-ribofuranosyl chloride (5), obtained in three steps from inosine, reacts with amines to yield uronamides. The subsequent reaction of such uronamides with amines at elevated temperatures displaces the purine 6-chloro group to yield, after deblocking, N-alkyl(or aryl)-N6-alk(ar)yl-adenosine-5'-uronamides. At the coronary artery A2 receptor the potency of N6-modified analogues of 1 is similar to that of the N6-substituted adenosine, rather than equal to or greater than 1. As agonists in the A2 receptor-mediated stimulation of adenylate cyclase in plasma membranes of PC12 pheochromocytoma cells or human platelets, N6-substituted analogues of 1 are intermediate between the high potency of 1 and the lower potency of the N6-substituted adenosines. At the A1 receptor of rat brain the potency of an N6-substituted analogue of 1 is often greater than that of the corresponding N6-substituted adenosine. At all four receptors, replacing the ethyl group of N-ethyl-N6-3-pentyladenosine-5'-uronamide by larger alkyl groups reduces potency; amides of secondary amines are inactive or have only marginal activity. Analogues of 1 containing a chiral center in the N6 substituent retain the stereoselectivity characteristic of each of the four receptors. Thus, at either A1 or A2 adenosine receptors, adenosine analogues interact with both the N6 and the C-5' receptor regions. However, the effects of N6 and C-5' modifications on potency are less than additive, evidence that the interaction of a substituent with its receptor region influences the interaction of other substituents with their respective receptor regions.
• Structure-Activity Relationships of N6-Benzyladenosine-5'-uronamides as A3-Selective Adenosine Agonists
  作者：Carola Gallo-Rodriguez、Xiao-duo Ji、Neli Melman、Barry D. Siegman、Lawrence H. Sanders、Jeraldine Orlina、Bilha Fischer、Quanlong Pu、Mark E. Olah

  DOI：10.1021/jm00031a014

  日期：1994.3

  Adenosine analogues modified at the 5'-position as uronamides and/or as N-6-benzyl derivatives were synthesized. These derivatives were examined for affinity in radioligand binding assays at the newly discovered rat brain A(3) adenosine receptor and at rat brain A(1) and Az, receptors. 5'Uronamide substituents favored AS selectivity in the order N-methyl > N-ethyl approximate to unsubstituted carboxamide > N-cyclopropyl. 5'-(N-Methylcarboxamido)-N-6-benzyladenosine was 37-56-fold more selective for Ag receptors. Potency at A(3) receptors was enhanced upon substitution of the benzyl substituent with nitro and other groups. 5'-N-Methyluronamides and N-6-(3-substituted-benzyl) adenosines are optimal for potency and selectivity at A(3) receptors. A series of 3-(halobenzyl)5'-N-ethyluronamide derivatives showed the order of potency at A(1) and A(2)a receptors of I similar to Br > Cl > F. At A(3) receptors the 3-F derivative was weaker than the other halo derivatives. 5'-N-Methyl-N-6- (3-iodobenzyl) adenosine displayed a K-i value of 1.1 nM at A(3) receptors and selectivity versus A(1) and A(2a), receptors of 50-fold. A series of methoxybenzyl derivatives showed that a C-methoxy group best favored A(3) selectivity. A 4-sulfobenzyl derivative was a specific ligand at A(3) receptors of moderate potency. An aryl amino derivative was prepared as a probe for radioiodination and receptor cross-linking.
• New Fluorescent Adenosine A₁-Receptor Agonists That Allow Quantification of Ligand−Receptor Interactions in Microdomains of Single Living Cells
  作者：Richard J. Middleton、Stephen J. Briddon、Yolande Cordeaux、Andrew S. Yates、Clare L. Dale、Michael W. George、Jillian. G. Baker、Stephen J. Hill、Barrie Kellam

  DOI：10.1021/jm061279i

  日期：2007.2.1

  Fluorescence spectroscopy is becoming a valuable addition to the array of techniques available for scrutinizing ligand-receptor interactions in biological systems. In particular, scanning confocal microscopy and fluorescence correlation spectroscopy (FCS) allow the noninvasive imaging and quantification of these interactions in single living cells. To address the emerging need for fluorescently labeled ligands to support these technologies, we have developed a series of red-emitting agonists for the human adenosine A(1)-receptor that, collectively, are N-6-aminoalkyl derivatives of adenosine or adenosine 5'-N-ethyl carboxamide. The agonists, which incorporate the commercially available fluorophore BODIPY [630/650], retain potent and efficacious agonist activity, as demonstrated by their ability to inhibit cAMP accumulation in chinese hamster ovary cells expressing the human adenosine A(1)-receptor. Visualization and confirmation of ligand-receptor interactions at the cell membrane were accomplished using confocal microscopy, and their suitability for use in FCS was demonstrated by quantification of agonist binding in small areas of cell membrane.