N-[[(3R)-5-chloro-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-2-(2,6-dimethoxyphenoxy)ethanamine;hydrochloride | 1416443-75-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[[(3R)-5-chloro-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-2-(2,6-dimethoxyphenoxy)ethanamine;hydrochloride
• CAS: 1416443-75-8
• 化学式: C₁₉H₂₂ClNO₅*ClH
• 分子量: 416.301
• InChiKey: SRZQASDTTLSGGK-BTQNPOSSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氯苯基乙酸酯 在 盐酸 、 aluminum (III) chloride 、 palladium on activated charcoal 、 四丁基溴化铵 、 水 、 氢气 、 potassium carbonate 、 三乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 异丁醇 、 水 、 N,N-二甲基甲酰胺 、 邻二氯苯 、 丙酮 为溶剂， 反应 238.0h， 生成 N-[[(3R)-5-chloro-2,3-dihydro-1,4-benzodioxin-3-yl]methyl]-2-(2,6-dimethoxyphenoxy)ethanamine;hydrochloride
  参考文献：
  名称：

  Affinity and activity profiling of unichiral 8-substituted 1,4-benzodioxane analogues of WB4101 reveals a potent and selective α1B-adrenoceptor antagonist

  摘要：

  Unichiral 8-substituted analogues of 2-[(2-(2,6-dimethoxyphenoxy)ethyl)aminomethyl]-1,4-benzodioxane (WB4101) were synthesized and tested for binding affinity at cloned human alpha(1a), alpha(1b)-and alpha(1d)-adrenoreceptor (alpha(1a)-, alpha(1b)-and alpha(1d)-AR) and at native rat 5-HT1A receptor and for antagonist affinity at MIA". affrand am-AR and at a2A/D-AR. Among the selected 8-substituents, namely fluorine, chlorine, methoxyl and hydroxyl, only the last caused significant decrease of alpha(1) binding affinity in comparison with the lead compound. Functional tests on the S isomers confirmed the detrimental effect of OH positioned in proximity to benzodioxane O(1). For the other three substituents (F, Cl, OMe), the alp and the am antagonist affinities were generally lower than the alpha(1a) and alpha(1d) binding affinities, but not the alpha(1B) antagonist affinity, which was similar and sensibly higher compared to alpha(1b) binding affinity in the case of F and OMe respectively. This trend confers significant alpha(1B)-AR selectivity, in particular, to the 8-methoxy analogue of (S)-WB4101, a new potent (pA(2) 9.58) alpha(1B)-AR antagonist. The S enantiomers of all the tested compounds were proved to act as al-AR inverse agonists in a vascular model. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.09.049