3-azido-3-deoxy-1,2-diacetoxy-α-D-ribofuranuronic acid methyl amide | 331729-04-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-azido-3-deoxy-1,2-diacetoxy-α-D-ribofuranuronic acid methyl amide
• 英文别名: 1,2-di-O-acetyl-3-azido-3-deoxy-D-ribofuranuronic acid methyl amide；3-azido-3-deoxy-1,2-diacetoxy-D-ribofuranuronic acid methyl amide；methyl 3-azido-3-deoxy-1,2-diacetyl-D-ribofuronamide；(2S,3S,4R)-3-azido-4,5-diacetoxytetrahydrofuran-2-carboxylic acid methylamide；1,2-bis-O-acetyl-3-azido-3-deoxy-D-ribofuranuronic acid methyl amide；[(3R,4S,5S)-2-acetyloxy-4-azido-5-(methylcarbamoyl)oxolan-3-yl] acetate
• CAS: 331729-04-5
• 化学式: C₁₀H₁₄N₄O₆
• 分子量: 286.244
• InChiKey: GJSBCBKQBUAXMY-ULFAAJNHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-azido-3-deoxy-1,2-diacetoxy-α-D-ribofuranuronic acid methyl amide 在 咪唑 、 ammonium sulfate 、 四丁基氟化铵 、 sodium methylate 、 三乙胺 、 三苯基膦 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 86.83h， 生成 (2S,3S,4R,5R)-3-(carbamoylamino)-4-hydroxy-5-[6-[(3-iodophenyl)methylamino]purin-9-yl]-N-methyloxolane-2-carboxamide
  参考文献：
  名称：

  Orthogonal Activation of the Reengineered A₃ Adenosine Receptor (Neoceptor) Using Tailored Nucleoside Agonists

  摘要：

  An alternative approach to overcome the inherent lack of specificity of conventional agonist therapy can be the reengineering of the GPCRs and their agonists. A reengineered receptor ( neoceptor) could be selectively activated by a modified agonist, but not by the endogenous agonist. Assisted by rhodopsin-based molecular modeling, we pinpointed mutations of the A(3) adenosine receptor (AR) for selective affinity enhancement following complementary modifications of adenosine. Ribose modifications examined included, at 3' : amino, aminomethyl, azido, guanidino, ureido; and at 5' : uronamido, azidodeoxy. N-6-Variations included 3-iodobenzyl, 5-chloro-2-methyloxybenzyl, and methyl. An N-6-3-iodobenzyl-3'-ureido adenosine derivative 10 activated phospholipase C in COS-7 cells (EC50 = 0.18 mu M) or phospholipase D in chick primary cardiomyocytes, both mediated by a mutant ( H272E), but not the wild-type, A(3)AR. The affinity enhancements for 10 and the corresponding 3'-acetamidomethyl analogue 6 were > 100-fold and > 20-fold, respectively. 10 concentration-dependently protected cardiomyocytes transfected with the neoceptor against hypoxia. Unlike 10, adenosine activated the wild-type A(3)AR (EC50 of 1.0 mu M), but had no effect on the H272E mutant A(3)AR (100 mu M). Compound 10 was inactive at human A(1), A(2A), and A(2B)ARs. The orthogonal pair comprising an engineered receptor and a modified agonist should be useful for elucidating signaling pathways and could be therapeutically applied to diseases following organ-targeted delivery of the neoceptor gene.

  DOI：

  10.1021/jm050968b
• 作为产物：
  描述：

  在 硫酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 18.5h， 生成 3-azido-3-deoxy-1,2-diacetoxy-α-D-ribofuranuronic acid methyl amide
  参考文献：
  名称：

  在人腺苷A3受体上合成的高效，选择性和水溶性激动剂。

  摘要：

  使用平行和定向合成的组合，发现了高效和选择性系列的腺苷A3激动剂。预期的肠胃外给药途径所需的高水溶性是通过存在一个或两个碱性胺官能团实现的。

  DOI：

  10.1016/j.bmcl.2006.01.088

文献信息

• Compounds for the treatment of ischemia
  申请人：——

  公开号：US20040198693A1

  公开（公告）日：2004-10-07

  A 3 agonists, methods of using such A 3 agonists and pharmaceutical compositions containing such A 3 agonists. The A 3 agonists are useful for the reduction of tissue damage resulting from tissue ischemia or hypoxia.

  A3激动剂，使用此类A3激动剂的方法以及含有此类A3激动剂的药物组合物。这些A3激动剂对于减少由组织缺血或缺氧引起的组织损伤是有用的。
• Purine derivatives for the treatment of ischemia
  申请人：Pfizer Products Inc.

  公开号：EP1241176A1

  公开（公告）日：2002-09-18

  A3 agonists having Formula I are described herein as well as methods of using such A3 agonists and pharmaceutical compositions containing such A3 agonists. The A3 agonists are useful for the reduction of tissue damage resulting from tissue ischemia or hypoxia.

  本文描述了具有式 I 的 A3 激动剂以及使用这种 A3 激动剂的方法和含有这种 A3 激动剂的药物组合物。 A3 激动剂可用于减少组织缺血或缺氧造成的组织损伤。
• Design and synthesis of 3′-ureidoadenosine-5′-uronamides: effects of the 3′-ureido group on binding to the A3 adenosine receptor
  作者：Lak Shin Jeong、Myong Jung Kim、Hea Ok Kim、Zhan-Guo Gao、Soo-Kyung Kim、Kenneth A. Jacobson、Moon Woo Chun

  DOI：10.1016/j.bmcl.2004.07.042

  日期：2004.10

  On the basis of high binding affinity at the A(3) adenosine receptor of 3'-aminoadenosine derivatives with hydrogen bonding donor ability, novel 3'-ureidoadenosine analogues were synthesized from 1,2:5,6-di-O-isopropylidene-D-glucose in order to lead to stronger hydrogen bonding than the corresponding 3'-aminoadeno sine derivatives. However, the synthesized 3'-ureidoadenosine analogues were totally devoid of binding affinity, because 3'-urea moiety caused steric and electrostatic repulsions at the binding site of the A(3) adenosine receptor, leading to conformational distortion. (C) 2004 Elsevier Ltd. All rights reserved.
• Exploring human adenosine A3 receptor complementarity and activity for adenosine analogues modified in the ribose and purine moiety
  作者：Philippe Van Rompaey、Kenneth A. Jacobson、Ariel S. Gross、Zhan-Guo Gao、Serge Van Calenbergh

  DOI：10.1016/j.bmc.2004.11.044

  日期：2005.2

  In this paper we investigated the influence on affinity, selectivity and intrinsic activity upon modification of the adenosine agonist scaffold at the 3- and 5'-positions of the ribofuranosyl moiety and the 2- and N-6-positions of the purine base. This resulted in the synthesis of various analogues, that is, 3-12 and 24-33, with good hA(3)AR selectivity and moderate-to-high affinities (as in 32, K-i = 27 nM). Interesting was the ability to tune the intrinsic activity depending on the substituent introduced at the 3'-position. (C) 2004 Elsevier Ltd. All rights reserved.
• 3‘-Aminoadenosine-5‘-uronamides:  Discovery of the First Highly Selective Agonist at the Human Adenosine A₃ Receptor
  作者：Michael P. DeNinno、Hiroko Masamune、Lois K. Chenard、Kenneth J. DiRico、Cynthia Eller、John B. Etienne、Jeanene E. Tickner、Scott P. Kennedy、Delvin R. Knight、Jimmy Kong、Joseph J. Oleynek、W. Ross Tracey、Roger J. Hill

  DOI：10.1021/jm0255724

  日期：2003.1.1

  Selective adenosine A(3) agonists have potential utility for the prevention of perioperative myocardial ischemic injury. Herein, we report on the discovery and synthesis of compound 7. This amino nucleoside agonist possesses unprecedented levels of selectivity for the human adenosine A(3) receptor.