(1'S,2'R,3'S,4'S,5'S)-4'-{6-[3-[5-(hydroxycarbonyl)-1-pentynyl]phenylmethylamino]-2-chloro-9-yl}-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide | 1037454-82-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (1'S,2'R,3'S,4'S,5'S)-4'-{6-[3-[5-(hydroxycarbonyl)-1-pentynyl]phenylmethylamino]-2-chloro-9-yl}-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide
• 英文别名: (1'S,2'R,3'S,4'S,5'S)-4'-[6-(3-[5-(hydroxycarbonyl)-1-pentynyl]phenylmethylamino)-2-chloropurin-9-yl]-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide；6-[3-[[[2-chloro-9-[(1S,2R,3S,4R,5S)-3,4-dihydroxy-5-(methylcarbamoyl)-2-bicyclo[3.1.0]hexanyl]purin-6-yl]amino]methyl]phenyl]hex-5-ynoic acid
• CAS: 1037454-82-2
• 化学式: C₂₆H₂₇ClN₆O₅
• 分子量: 538.991
• InChiKey: HQMYBQYXNBGGQE-LXILBCFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  163
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  在 水 、 三氟乙酸 作用下， 以 甲醇 为溶剂， 反应 16.0h， 生成 (1'S,2'R,3'S,4'S,5'S)-4'-{6-[3-[5-(methoxycarbonyl)-1-pentynyl]phenylmethylamino]-2-chloro-9-yl}-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide 、 (1'S,2'R,3'S,4'S,5'S)-4'-{6-[3-[5-(hydroxycarbonyl)-1-pentynyl]phenylmethylamino]-2-chloro-9-yl}-2',3'-dihydroxybicyclo[3.1.0]hexane-1'-carboxylic acid N-methylamide
  参考文献：
  名称：

  [EN] PURINE DERIVATIVES AS A3 RECEPTOR- SELECTIVE AGONISTS
  [FR] DÉRIVÉS DE PURINE EN TANT QU'AGONISTES SÉLECTIFS DU RÉCEPTEUR A3

  摘要：

  揭示了(N)-甲烷卡巴腺嘌呤核苷，如式(I)所示，作为高效的A3腺苷受体激动剂，包括这种核苷的药物组合物，以及这些核苷的使用方法，其中R1-R6如规范中所定义。这些核苷表现出与人类和小鼠腺苷受体的A3对A1受体的激动剂类似的选择性，并可用于治疗多种疾病，例如炎症、心肌缺血、中风、哮喘、糖尿病和心律失常。

  公开号：

  WO2009123881A1

文献信息

• [EN] PURINE DERIVATIVES AS A3 RECEPTOR- SELECTIVE AGONISTS<br/>[FR] DÉRIVÉS DE PURINE EN TANT QU'AGONISTES SÉLECTIFS DU RÉCEPTEUR A3
  申请人：US HEALTH

  公开号：WO2009123881A1

  公开（公告）日：2009-10-08

  Disclosed are (N)-methanocarba adenine nucleosides, e.g., of formula (I) as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. These nucleosides exhibit similar selectivities as agonists of the A3 versus the A1 receptor for both human and mouse adenosine receptors, and are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias.

  揭示了(N)-甲烷卡巴腺嘌呤核苷，如式(I)所示，作为高效的A3腺苷受体激动剂，包括这种核苷的药物组合物，以及这些核苷的使用方法，其中R1-R6如规范中所定义。这些核苷表现出与人类和小鼠腺苷受体的A3对A1受体的激动剂类似的选择性，并可用于治疗多种疾病，例如炎症、心肌缺血、中风、哮喘、糖尿病和心律失常。
• Design of (N)-methanocarba adenosine 5′-uronamides as species-independent A3 receptor-selective agonists
  作者：Artem Melman、Zhan-Guo Gao、Deepmala Kumar、Tina C. Wan、Elizabeth Gizewski、John A. Auchampach、Kenneth A. Jacobson

  DOI：10.1016/j.bmcl.2008.04.001

  日期：2008.5

  2-Chloro-5'-N-methylcarboxamidoadenosine analogues containing the (N)-methanocarba (bicyclo[3.1.0] hexane) ring system as a ribose substitute display increased selectivity as agonists of the human A(3) adenosine receptor ( AR). However, the selectivity in mouse was greatly reduced due to an increased tolerance of this ring system at the mouse A(1)AR. Therefore, we varied substituents at the N-6 and C2 positions in search of compounds that have improved A(3)AR selectivity and are species independent. An N-6-methyl analogue was balanced in affinity at mouse A(1)/A(3)ARs, with high selectivity in comparison to the A(2A)AR. Substitution of the 2-chloro atom with larger and more hydrophobic substituents, such as iodo and alkynyl groups, tended to increase the A(3)AR selectivity (up to 430-fold) in mouse and preserve it in human. Extended and chemically functionalized alkynyl chains attached at the C2 position of the purine moiety preserved A3AR selectivity more effectively than similar chains attached at the 3-position of the N-6-benzyl group. Published by Elsevier Ltd.