2-(2,6-dimethoxy-phenoxy)ethylamine hydrochloride | 87780-27-6

• 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: 2-(2,6-dimethoxy-phenoxy)ethylamine hydrochloride
• 英文别名: 2-(2,6-dimethoxyphenoxy)ethylamine hydrochloride；2-(2,6-Dimethoxyphenoxy)ethanamine hydrochloride；2-(2,6-dimethoxyphenoxy)ethanamine;hydrochloride
• CAS: 87780-27-6
• 化学式: C₁₀H₁₅NO₃*ClH
• mdl: MFCD11505631
• 分子量: 233.695
• InChiKey: GIOOBTIDHYCEOG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  53.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(2,6-dimethoxy-phenoxy)ethylamine hydrochloride 在 盐酸 、 sodium tetrahydroborate 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 12.0h， 生成 cis-3-<<<2-(2,6-dimethoxyphenoxy)ethyl>amino>methyl>-4-chromanol
  参考文献：
  名称：

  Structure-activity relationships in 1,4-benzodioxan-related compounds. Investigation on the role of the dehydrodioxane ring on .alpha.1-adrenoreceptor blocking activity

  摘要：

  Several analogues of 2-[[[2-(2,6-dimethoxyphenoxy)ethyl]amino]methyl]-1,4-benzodioxa n (WB 4101, 1) were prepared and evaluated for their blocking activity on alpha 1- and alpha 2-adrenoreceptors in the isolated rat vas deferens. The results were compared with those obtained for 1 and benoxathian (2). It was shown that the two oxygens at positions 1 and 4 may have a different role in receptor binding. It seems that the oxygen at position 4 as such does not contribute to the binding while it is important in stabilizing an optimal conformation for drug-receptor interaction mechanism. On the other hand, the oxygen at position 1 might interact with a receptor polar pocket of reduced size by way of a donor-acceptor dipolar interaction. Furthermore, it was shown that replacement of the dehydrodioxane ring of 1 by a phenyl or a pyrrole nucleus causes a significant decrease in activity.

  DOI：

  10.1021/jm00120a009

文献信息

• DE1913199
  申请人：——

  公开号：——

  公开（公告）日：——
• .beta.-Adrenergic blocking agents. 17. 1-Phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propanols
  作者：L. H. Smith、H. Tucker

  DOI：10.1021/jm00222a022

  日期：1977.12

  The synthesis is described of a series of derivatives of 1-phenoxy-3-phenoxyalkylamino-2-propanols and 1-alkoxyalkylamino-3-phenoxy-2-propranols. The compounds were investigated for their beta-adrenoceptor blocking properties and many showed a surprising degree of cardioselectivity when tested in vivo in anesthetized cats for their effects on an isoproterenol-induced tachycardia and depressor response. The structure-activity relationship shown by this series of compounds is related to that of known cardioselective analogues and a possible reason for their cardioselectivity is discussed.
• Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 7. Selectivity of 4-Phenylchroman Analogues for α₁−Adrenoreceptor Subtypes
  作者：Wilma Quaglia、Maria Pigini、Alessandro Piergentili、Mario Giannella、Francesco Gentili、Gabriella Marucci、Antonio Carrieri、Angelo Carotti、Elena Poggesi、Amedeo Leonardi、Carlo Melchiorre

  DOI：10.1021/jm011066n

  日期：2002.4.1

  WB4101 (1)-related compounds 5-10 were synthesized, and their biological profile at alpha(1)-adrenoreceptor (AR) subtypes and 5-HT1A serotoninergic receptors was assessed by binding assays in Chinese hamster ovary and HeLa cell membranes expressing the human cloned receptors. Moreover, their receptor selectivity was further determined in functional experiments in isolated rat prostate (alpha(1A)), vas deferens (alpha(1A)), aorta (alpha(1D)), and spleen (alpha(1B)). In functional assays, compound 5 was the most potent at alpha(1D)-ARs with a reversed selectivity profile (alpha(1D) > alpha(1A) > alpha(1B)) relative to both prototype 1 and phendioxan (2) (alpha(1A) > alpha(1D) > alpha(1D)), whereas compound 8, bearing a carbonyl moiety at position 1, was the most potent at alpha(1)-ARs with a selectivity profile similar to that of prototypes. The least potent of the series was the trans isomer 6, suggesting that optimum alpha(1)-AR blocking activity in this series is associated with a cis relationship between the 2-side chain and the 4-phenyl ring rather than a trans relationship as previously observed for the 2-side chain and the 3-phenyl ring in 2 and related compounds. Binding affinity results were not in complete agreement with the selectivity profiles deriving from functional experiments. Although a firm explanation was not available, neutral and negative antagonism and receptor dimerization were considered as two possibilities to account for the difference between binding and functional affinities. Finally, compound 5 was selected for a modeling study in comparison with 1, mephendioxan (3), and open phendioxan (4) to achieve information on the physicochemical interactions that account for its high affinity toward alpha(1d/D)-ARs.
• Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 6. Role of the Dioxane Unit on Selectivity for α₁-Adrenoreceptor Subtypes
  作者：Wilma Quaglia、Maria Pigini、Alessandro Piergentili、Mario Giannella、Gabriella Marucci、Elena Poggesi、Amedeo Leonardi、Carlo Melchiorre

  DOI：10.1021/jm9910324

  日期：1999.7.1

  WB 4101-related benzodioxans 3-9 were synthesized, and their biological profiles at alpha(1)-adrenoreceptor subtypes and 5-HT1A serotoninergic receptors were assessed by binding assays in CHO and HeLa cells membranes expressing the human cloned receptors. Furthermore, receptor selectivity of selected benzodioxan derivatives was further determined in functional experiments in isolated rat vas deferens ((alpha(1A)) and aorta (alpha(1D)) and guinea pig spleen (alpha(1B)), in additional receptor binding assays in rat cortex membranes containing alpha(2)-adrenoreceptors and 5-HT2 serotoninergic receptors, and in rat striatum membranes containing D-2 dopaminergic receptors. An analysis of the results of receptor binding experiments for benzodioxan-modified derivatives 3-9 showed high affinity and selectivity toward the alpha(1a)-adrenoreceptor subtype for compounds 3-5 and 7 and a reversed selectivity profile for 9, which was a selective aid antagonist. Furthermore, the majority of structural modifications performed on the prototype 1 (WB 4101) led to a marked decrease in the affinity for 5-HT1A serotoninergic receptors, which may have relevance in the design of selective alpha(1A)-adrenoreceptor antagonists. The exception to these findings was the chromene derivative 8, which exhibited a 5-HT1A partial agonist profile.