2-{6-[((3R)oxolan-3-yl)amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2,6-dichlorophenylthio)methyl] oxolane-3,4-diol

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 2-{6-[((3R)oxolan-3-yl)amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2,6-dichlorophenylthio)methyl] oxolane-3,4-diol
• 英文别名: 2-{6-[((3R)oxolan-3-yl)amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2,6-dichlorophenylthio)methyl]oxolane-3,4-diol；(2S,3S,4R,5R)-2-[(2,6-dichlorophenyl)sulfanylmethyl]-5-[6-[[(3R)-oxolan-3-yl]amino]purin-9-yl]oxolane-3,4-diol
• 化学式: C₂₀H₂₁Cl₂N₅O₄S
• 分子量: 498.39
• InChiKey: SAWJMCIHYCLBTD-ACLZQREGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  Tecadenoson 在 偶氮二甲酸二异丙酯 、 polystyrene bound triphenylphosphine 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.5h， 生成 2-{6-[((3R)oxolan-3-yl)amino]purin-9-yl}(4S,5S,2R,3R)-5-[(2,6-dichlorophenylthio)methyl] oxolane-3,4-diol
  参考文献：
  名称：

  Structure–affinity relationships of 5 ′ -aromatic ethers and 5 ′ -aromatic sulfides as partial A 1 adenosine agonists, potential supraventricular anti-arrhythmic agents

  摘要：

  Atrial fibrillation (AF) is the most commonly encountered sustained clinical arrhythmia with an estimated 2.3 million cases in the US (2001). A, adenosine receptor agonists can slow the electrical impulse propagation through the atrioventricular (AV) node (i.e., negative dromotropic effect) resulting in prolongation of the stimulus-to-His bundle (S-H) interval to potentially reduce ventricular rate. Compounds that are full agonists of the A, adenosine receptor can cause high grade AV block. Therefore, it is envisioned that a compound that is a partial agonist of the A, adenosine receptor could avoid this deleterious effect. 5' Phenyl sulfides (e.g., 17, EC50 = 1.26 muM) and phenyl ethers (e.g., 28, EC50 = 0.2 muM) are partial agonists with respect to their AV nodal effects in guinea pig isolated hearts. Additional affinity, GTPgammaS binding data suggesting partial activity of the A(1) adenosine receptor, and PK results for 5' modified adenosine derivatives are shown. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.04.096

文献信息

• Method of identifying partial adenosine A1 receptor agonists and their use in the treatment of arrhythmias
  申请人：——

  公开号：US20010008883A1

  公开（公告）日：2001-07-19

  The present invention provides a method for identifying parital adenosine A1 receptor agonists that are useful in the treatment of arrhythmias. Partial adenosine A1 receptor agonists and methods for using partial adenosine A1 receptor agonists to treat arrhythmias in mammals.

  本发明提供了一种用于识别对治疗心律失常有用的部分腺苷A1受体激动剂的方法。部分腺苷A1受体激动剂以及使用部分腺苷A1受体激动剂治疗哺乳动物心律失常的方法。
• Partial or full A1 agonists - N6 heterocyclic 5' thio substituted adenosine derivatives
  申请人：Zablocki A. Jeff

  公开号：US20050054605A1

  公开（公告）日：2005-03-10

  N 6 heterocyclic 5′ modified adenosine derivatives that are adenosine A 1 receptor partial or full agonists, and as such, are useful for modifying cardiac activity, modifying adipocyte function, treating central nervous system disorders, and treating diabetic disorders and obesity in mammals, and especially in humans.

  N6杂环5'修饰腺苷衍生物是腺苷A1受体的部分或全激动剂，因此对于调节心脏活动、调节脂肪细胞功能、治疗中枢神经系统疾病以及治疗哺乳动物（特别是人类）的糖尿病和肥胖症非常有用。
• PARTIAL OR FULL A1 AGONISTS - N6 HETEROCYCLIC 5'-THIO SUBSTITUTED ADENOSINE DERIVATIVES
  申请人：CV THERAPEUTICS, INC.

  公开号：EP1233973A1

  公开（公告）日：2002-08-28
• US6576620B2
  申请人：——

  公开号：US6576620B2

  公开（公告）日：2003-06-10
• [EN] PARTIAL OR FULL A1 AGONISTS - N<6> HETEROCYCLIC 5'-THIO SUBSTITUTED ADENOSINE DERIVATIVES<br/>[FR] DERIVES DE N<6>-ADENOSINE HETEROCYCLIQUE A SUBSTITUTION 5'-THIO, AGONISTES D'A1 ENTIERS OU PARTIELS
  申请人：CV THERAPEUTICS INC

  公开号：WO2001040246A1

  公开（公告）日：2001-06-07

  N6 heterocyclic 5' modified adenosine derivatives that are adenosine A¿1? receptor partial or full agonists, and as such, are useful for modifying cardiac activity, modifying adipocyte function, treating central nervous system disorders, and treating diabetic disorders and obesity in mammals, and especially in humans.