(2S,3S,4R,5R) 3-azido-4-hydroxy-5-(6-methylamino-purin-9-yl)-tetrahydro-furan-2-carboxylic acid methylamide | 786665-77-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3S,4R,5R) 3-azido-4-hydroxy-5-(6-methylamino-purin-9-yl)-tetrahydro-furan-2-carboxylic acid methylamide
• 英文别名: 3-azido-5-(6-methylaminopurin-9-yl)-4-hydroxy-tetrahydro-furan-2-carboxylic acid methyl amide；(2S,3S,4R,5R)-3-azido-4-hydroxy-N-methyl-5-[6-(methylamino)purin-9-yl]oxolane-2-carboxamide
• CAS: 786665-77-8
• 化学式: C₁₂H₁₅N₉O₃
• 分子量: 333.31
• InChiKey: DHYPOFDIQJEGKY-HIFLKKFUSA-N

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：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  129
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S,3S,4R,5R) 3-azido-4-hydroxy-5-(6-methylamino-purin-9-yl)-tetrahydro-furan-2-carboxylic acid methylamide 在 咪唑 、 ammonium hydroxide 、 sodium methylate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 63.0h， 生成 3-ureido-5-(6-methylaminopurin-9-yl)-4-t-butyldimethylsiloxy-tetrahydro-furan-2-carboxylic acid methyl amide
  参考文献：
  名称：

  Design and synthesis of 3′-ureidoadenosine-5′-uronamides: effects of the 3′-ureido group on binding to the A3 adenosine receptor

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.07.042
• 作为产物：
  描述：

  1,2:5,6-di-O-isopropylidene-3-O-triflyl-α-D-glucofuranose 在 吡啶 、 ruthenium trichloride 、 sodium periodate 、 甲酸 、 sodium azide 、 草酰氯 、 三氟甲磺酸三甲基硅酯 、 sodium methylate 、 溶剂黄146 、 N,N-二甲基甲酰胺 作用下， 以 1,4-二氧六环 、 甲醇 、 四氯化碳 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 98.0h， 生成 (2S,3S,4R,5R) 3-azido-4-hydroxy-5-(6-methylamino-purin-9-yl)-tetrahydro-furan-2-carboxylic acid methylamide
  参考文献：
  名称：

  Design and synthesis of 3′-ureidoadenosine-5′-uronamides: effects of the 3′-ureido group on binding to the A3 adenosine receptor

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2004.07.042

文献信息

• Compounds for the treatment of ischemia
  申请人：DeNinno P. Michael

  公开号：US20050171049A1

  公开（公告）日：2005-08-04

  A 3 agonists having Formula I are described herein as well as 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.

  本文描述了具有I式的A3激动剂，以及使用这种A3激动剂的方法和含有这种A3激动剂的制药组合物。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。
• 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.
• 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.
• Orthogonal Activation of the Reengineered A₃ Adenosine Receptor (Neoceptor) Using Tailored Nucleoside Agonists
  作者：Zhan-Guo Gao、Heng T. Duong、Tatiana Sonina、Soo-Kyung Kim、Philippe Van Rompaey、Serge Van Calenbergh、Liaman Mamedova、Hea Ok Kim、Myong Jung Kim、Ae Yil Kim、Bruce T. Liang、Lak Shin Jeong、Kenneth A. Jacobson

  DOI：10.1021/jm050968b

  日期：2006.5.1

  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.