2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>adenosine | 141345-18-8

• 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: 2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>adenosine
• 英文别名: 2-[2-(1-hydroxycyclohexyl)-1-ethyn-1-yl]adenosine；2-[2-(1-hydroxycyclohexyl)ethyn-1-yl]adenosine；2-[(1-hydroxycyclohexane-1-yl)ethynyl]adenosine；(2R,3R,4S,5R)-2-[6-amino-2-[2-(1-hydroxycyclohexyl)ethynyl]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol
• CAS: 141345-18-8
• 化学式: C₁₈H₂₃N₅O₅
• 分子量: 389.411
• InChiKey: LXNMJIMFUJADFH-IWCJZZDYSA-N

物化性质

• 沸点：
  794.4±70.0 °C(Predicted)
• 密度：
  1.68±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  160
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>adenosine 在 盐酸 、 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 14.5h， 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 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 水 、 三乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 31.5h， 生成 2-<2-(1-hydroxycyclohexyl)-1-ethyn-1-yl>adenosine
  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

• 2-substituted adenosine derivatives and pharmaceutical compositions for
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：US05189027A1

  公开（公告）日：1993-02-23

  Disclosed herein are a novel 2-substituted adenosine derivative having the following formula [I] ##STR1## wherein R represents a hydrogen atom or a hydroxyl group, m is an integer of 2 to 7, n is 0 or an integer of 1 to 3, and R.sup.1, R.sup.2 and R.sup.3, which may be the same or different, each independently represent a hydrogen atom, a hydroxy protective group or a phosphoric acid residue, and salts thereof. The above compounds are excellent in a circulation ameliorating effect such as a vasodepressor activity, and have high selectivity for A.sub.2 receptors, but cause less undesirable side effects such as a suppresssive effect on the heart. They are therefore effective when used in pharmaceutical compositions for circulatory diseases.

  本文披露了一种新型的2-取代腺苷衍生物，其具有以下式[I]： 其中R代表氢原子或羟基，m为2到7的整数，n为0或1到3的整数，R^1、R^2和R^3，可以相同也可以不同，分别代表氢原子、羟基保护基团或磷酸残基，以及它们的盐。上述化合物在循环改善效果方面表现出色，如血管扩张活性，并且对A.sub.2受体具有高选择性，但引起的不良副作用较少，如对心脏的抑制作用。因此，在循环疾病的药物组合物中使用时具有显著疗效。
• NOVEL 2-ALKYNYL-N9-PROPARGYLADENINE AND MEDICINAL USE THEREOF
  申请人：Endo Kazuki

  公开号：US20130245046A1

  公开（公告）日：2013-09-19

  In the present invention, a novel 2-alkynyl-N9-propargyladenine represented by formula (I) wherein R 1 represents a halogen atom, a furyl group, or a triazolyl group; R 2 and R 3 each represents a hydrogen atom or a C1-8 alkyl group, or form a cycloalkyl group by bonding to each other; and X represents a hydrogen atom or a hydroxyl group, or a pharmaceutically acceptable salt thereof, has a stronger and longer-lasting effect as a therapeutic agent for Parkinsonian syndromes.

  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。
• 2-Substituted adenosine derivatives and pharmaceutical compositions for circulatory diseases
  申请人：Yamasa Shoyu Kabushiki Kaisha

  公开号：EP0488336A1

  公开（公告）日：1992-06-03

  Disclosed herein are a novel 2-substituted adenosine derivative having the following formula [I] wherein R represents a hydrogen atom or a hydroxyl group, m is an integer of 2 to 7, n is 0 or an integer of 1 to 3, and R¹, R² and R³, which may be the same or different, each independently represent a hydrogen atom, a hydroxy protective group or a phosphoric acid residue, and salts thereof. The above compounds are excellent in a circulation ameliorating effect such as a vasodepressor activity, and have high selectivity for A₂ receptors, but cause less undesirable side effects such as a suppressive effect on the heart. They are therefore effective when used in pharmaceutical compositions for circulatory diseases.

  本文公开了具有下式[I]的新型 2-取代腺苷衍生物 其中 R 代表氢原子或羟基，m 为 2-7 的整数，n 为 0 或 1-3 的整数，R¹、R² 和 R³（可以相同或不同）各自独立地代表氢原子、羟基保护基团或磷酸残基、 及其盐类。 上述化合物具有良好的改善血液循环的作用，如血管舒张活性，对 A₂受体具有高选择性，但对心脏的抑制作用等不良副作用较小。因此，将它们用于治疗循环系统疾病的药物组合物中非常有效。
• MEDICINAL COMPOSITIONS FOR TREATING EYE DISEASES
  申请人：YAMASA CORPORATION

  公开号：EP1110554A1

  公开（公告）日：2001-06-27

  Medicinal compositions for treating eye diseases which contain as the active ingredient 2-alkynyladenosine derivatives having an acetylene union at the 2-position of adenine base. Having a long-lasting and remarkable effect of lowering ocular tension, these compositions are useful as remedies for eye diseases accompanying increased ocular tension or optic nerve failures, such as glaucoma and hypertonia oculi.

  治疗眼疾的药物组合物，其活性成分为腺嘌呤基 2 位上有乙炔结合的 2-炔基腺苷衍生物。这些复方制剂具有降低眼球张力的持久而显著的效果，可用于治疗伴有眼球张力增高或视神经衰竭的眼病，如青光眼和眼球过度紧张症。
• 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.