9-(2,3,5-tri-O-acetyl-1-β-D-ribofuranosyl)-6-chloro-2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>purine | 141345-32-6

• 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: 9-(2,3,5-tri-O-acetyl-1-β-D-ribofuranosyl)-6-chloro-2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>purine
• 英文别名: 6-chloro-2-[2-(1-hydroxycyclohexyl)-1-ethyn-1-yl]-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine；9-(2,3,5-tri-O-acetyl-1-β-D-ribofuranosyl)-6-chloro-2-[2-(1-hydroxycyclohexyl)ethyn-1-yl]purine；[(2R,3R,4R,5R)-3,4-diacetyloxy-5-[6-chloro-2-[2-(1-hydroxycyclohexyl)ethynyl]purin-9-yl]oxolan-2-yl]methyl acetate
• CAS: 141345-32-6
• 化学式: C₂₄H₂₇ClN₄O₈
• 分子量: 534.953
• InChiKey: MDZSPHNIXHKLCJ-UGTJMOTHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  152
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  9-(2,3,5-tri-O-acetyl-1-β-D-ribofuranosyl)-6-chloro-2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>purine 在 盐酸 、 ammonium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 8-bromo-2-[2-(1-hydroxycyclohexyl)-1-ethyn-1-yl]-N⁹-propargyladenine
  参考文献：
  名称：

  NOVEL 2-ALKYNYL-N9-PROPARGYLADENINE AND MEDICINAL USE THEREOF

  摘要：

  本发明涉及一种新型2-炔基-N9-丙炔基腺嘌呤，其化学式为（I），其中R1代表卤素原子、呋喃基或三唑基；R2和R3分别代表氢原子或C1-8烷基，或通过相互结合形成环烷基；X代表氢原子或羟基，或其药学上可接受的盐。该化合物作为帕金森综合症治疗剂具有更强和更持久的效果。

  公开号：

  US20130245046A1
• 作为产物：
  描述：

  炔环己醇 、 2',3',5'-三-O-乙酰-6-氯-2-碘嘌呤核苷 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 23.5h， 以105 mg的产率得到9-(2,3,5-tri-O-acetyl-1-β-D-ribofuranosyl)-6-chloro-2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>purine
  参考文献：
  名称：

  8-Substituted 2-alkynyl-N9-propargyladenines as A2A adenosine receptor antagonists

  摘要：

  Structure-activity relationships of 2-alkynyladenine derivatives were explored by varying substituents at the 9-, 8- and 2-positions of the purine moiety in order to optimize A(2A) adenosine receptor antagonist activity in vitro. A propargyl group at the 9-position was found to be important for A2A antagonist activity, and the introduction of a halogen, aryl, or heteroaryl at the 8-position further enhanced activity. A series of 8-substituted 2-alkynyl-N-9-propargyladenine derivatives exhibited potent antagonist activity, with IC50 values in the low nM range. Compound 4a from this series was found to be orally active at a dose of 3 mg/kg in a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model of Parkinson's disease. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.041

文献信息

• Nucleosides and nucleotides. 107. 2-(Cycloalkylalkynyl)adenosines: adenosine A2 receptor agonists with potent antihypertensive effects
  作者：Toichi Abiru、Takanori Miyashita、Yohko Watanabe、Toyofumi Yamaguchi、Haruhiko Machida、Akira Matsuda

  DOI：10.1021/jm00090a017

  日期：1992.6

  Adenosine receptor-binding profiles in rat brain tissues and antihypertensive effects in spontaneously hypertensive rats (SHR) of a series of 2-(cycloalkylalkynyl)adenosines (2-CAAs) and their congeners are described. The structure-activity relationship of this series of compounds is discussed, focusing on the length of the alkynyl side chain and bulkiness of the terminal cycloalkyl substituents in terms of binding activity and cardiovascular effects. All the 2-CAAs had a preferential affinity for A2 receptors. Of these derivatives, 2-(3-cyclopentyl-1-propyn-1-yl)adenosine (10b) exhibited the most selective affinity for A2 receptors (K(i) ratio: A1/A2 = 70) on the basis of receptor binding. In the C-2 binding region of adenosine, compounds often have potent and/or selective A2 activity from introduction of an acetylenic group at the C-2 position followed by one methylene residue further followed by a hydrophobic substituent such as a cycloalkyl ring at the terminal position of the alkynyl side chain. Intravenous injection of 10b up to 100-mu-g/kg had a potent hypotensive effect without a marked decrease in heart rate in anesthetized SHR. Compounds 10j-s, with a hydroxyl group in the C-3" position of the alkynyl side chain, had a potent affinity for both A1 and A2 receptors, but they were not highly selective for A2 receptors. These compounds caused a marked bradycardia upon intravenous administration in anesthetized SHR. Oral administration of 10b (0.1-1 mg/kg) had a potent and long-lasting antihypertensive effect in conscious SHR.
• US8791126B2
  申请人：——

  公开号：US8791126B2

  公开（公告）日：2014-07-29