2-[benzyl(2-phenoxyethyl)amino]-1-ethanol | 449195-24-8

• 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: 2-[benzyl(2-phenoxyethyl)amino]-1-ethanol
• 英文别名: 2-[benzyl-(2-phenoxy-ethyl)-amino]-ethanol；2-[Benzyl-(2-phenoxy-aethyl)-amino]-aethanol；2-[Benzyl(2-phenoxyethyl)amino]ethanol
• CAS: 449195-24-8
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: YEHMAQIEMAKATA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.294
• 拓扑面积：
  32.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[benzyl(2-phenoxyethyl)amino]-1-ethanol 在 盐酸 、 氯化亚砜 作用下， 以 苯 为溶剂， 反应 8.25h， 以22%的产率得到SKF 513 hydrochloride
  参考文献：
  名称：

  Structure–Activity relationships among novel phenoxybenzamine-Related β-Chloroethylamines

  摘要：

  A series of beta-chloroethylamines 5-18, structurally related to the irreversible alpha(1)-adrenoceptor antagonist phenoxy-benzamine [PB, N-benzyl-N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl)amine hydrochloride, 1] and the competitive antagonist WB4101 [N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-N-[2-(2,6-dimethoxyphenoxy)ethyl]amine hydrochloride, 2], were synthesized and evaluated for their activity at alpha-adrenoceptors of the epididymal and the prostatic portion of young CD rat vas deferens. All compounds displayed irreversible antagonist activity. Most of them showed similar antagonism at both alpha(1)- and alpha(2)-adrenoceptors, whereas compounds 13 and 18, lacking substituents on both the phenoxy group and the oxyamino carbon chain, displayed a moderate alpha(1)-adrenoceptor selectivity (10-35 times), which was comparable to that of PB. Compounds 14 and 15, belonging to the benzyl series and bearing, respectively, a 2-ethoxyphenoxy and a 2-i-propoxyphenoxy moiety, were the most potent alpha(1)-adrenoceptor antagonists with an affinity value similar to that Of PB (pIC(50) values of 7.17 and 7.06 versus 7.27). Interestingly, several compounds were able to distinguish two alpha(1)-adrenoceptor subtypes in the epididymal tissue, as revealed by the discontinuity of their inhibition curves. A mean ratio of 24:76 for these alpha(1)-adrenoceptors was determined from compounds 8-10, 12, and 15-17. Furthermore, compounds 9, 10, 12, 16a, and 16b showed higher affinity towards the minor population of receptors, whereas compounds 8, 15, and 17 preferentially inhibited the major population of alpha(1)-adrenoceptors. In addition, selected pharmacological experiments demonstrated the complementary antagonism of the two series of compounds and their different, preferential affinity for one of the two alpha(1)-adrenoceptor subtypes. In conclusion, we found beta-chloroethylamines that demonstrate a multiplicity of alpha(1)-adrenoceptors in the epididymal portion of young CD rat vas deferens and, as a consequence, they are possible useful tools for alpha(1)-adrenoceptor characterization. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00395-9
• 作为产物：
  描述：

  N-benzyl-2-phenoxyacetamide 在 dimethyl sulfide borane 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 反应 88.0h， 生成 2-[benzyl(2-phenoxyethyl)amino]-1-ethanol
  参考文献：
  名称：

  Structure–Activity relationships among novel phenoxybenzamine-Related β-Chloroethylamines

  摘要：

  A series of beta-chloroethylamines 5-18, structurally related to the irreversible alpha(1)-adrenoceptor antagonist phenoxy-benzamine [PB, N-benzyl-N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl)amine hydrochloride, 1] and the competitive antagonist WB4101 [N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-N-[2-(2,6-dimethoxyphenoxy)ethyl]amine hydrochloride, 2], were synthesized and evaluated for their activity at alpha-adrenoceptors of the epididymal and the prostatic portion of young CD rat vas deferens. All compounds displayed irreversible antagonist activity. Most of them showed similar antagonism at both alpha(1)- and alpha(2)-adrenoceptors, whereas compounds 13 and 18, lacking substituents on both the phenoxy group and the oxyamino carbon chain, displayed a moderate alpha(1)-adrenoceptor selectivity (10-35 times), which was comparable to that of PB. Compounds 14 and 15, belonging to the benzyl series and bearing, respectively, a 2-ethoxyphenoxy and a 2-i-propoxyphenoxy moiety, were the most potent alpha(1)-adrenoceptor antagonists with an affinity value similar to that Of PB (pIC(50) values of 7.17 and 7.06 versus 7.27). Interestingly, several compounds were able to distinguish two alpha(1)-adrenoceptor subtypes in the epididymal tissue, as revealed by the discontinuity of their inhibition curves. A mean ratio of 24:76 for these alpha(1)-adrenoceptors was determined from compounds 8-10, 12, and 15-17. Furthermore, compounds 9, 10, 12, 16a, and 16b showed higher affinity towards the minor population of receptors, whereas compounds 8, 15, and 17 preferentially inhibited the major population of alpha(1)-adrenoceptors. In addition, selected pharmacological experiments demonstrated the complementary antagonism of the two series of compounds and their different, preferential affinity for one of the two alpha(1)-adrenoceptor subtypes. In conclusion, we found beta-chloroethylamines that demonstrate a multiplicity of alpha(1)-adrenoceptors in the epididymal portion of young CD rat vas deferens and, as a consequence, they are possible useful tools for alpha(1)-adrenoceptor characterization. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00395-9

文献信息

• US2688638
  申请人：——

  公开号：——

  公开（公告）日：——
• Adrenergic Blocking Agents. II. N-(2-Chloroethyl)-N-(2-phenoxyethyl)-amine Hydrochlorides¹
  作者：William S. Gump、Edward J. Nikawitz

  DOI：10.1021/ja01165a004

  日期：1950.9
• Structure–Activity relationships among novel phenoxybenzamine-Related β-Chloroethylamines
  作者：Dario Giardinà、Mauro Crucianelli、Piero Angeli、Michela Buccioni、Ugo Gulini、Gabriella Marucci、Gianni Sagratini、Carlo Melchiorre

  DOI：10.1016/s0968-0896(01)00395-9

  日期：2002.5

  A series of beta-chloroethylamines 5-18, structurally related to the irreversible alpha(1)-adrenoceptor antagonist phenoxy-benzamine [PB, N-benzyl-N-(2-chloroethyl)-N-(1-methyl-2-phenoxyethyl)amine hydrochloride, 1] and the competitive antagonist WB4101 [N-(2,3-dihydro-1,4-benzodioxin-2-ylmethyl)-N-[2-(2,6-dimethoxyphenoxy)ethyl]amine hydrochloride, 2], were synthesized and evaluated for their activity at alpha-adrenoceptors of the epididymal and the prostatic portion of young CD rat vas deferens. All compounds displayed irreversible antagonist activity. Most of them showed similar antagonism at both alpha(1)- and alpha(2)-adrenoceptors, whereas compounds 13 and 18, lacking substituents on both the phenoxy group and the oxyamino carbon chain, displayed a moderate alpha(1)-adrenoceptor selectivity (10-35 times), which was comparable to that of PB. Compounds 14 and 15, belonging to the benzyl series and bearing, respectively, a 2-ethoxyphenoxy and a 2-i-propoxyphenoxy moiety, were the most potent alpha(1)-adrenoceptor antagonists with an affinity value similar to that Of PB (pIC(50) values of 7.17 and 7.06 versus 7.27). Interestingly, several compounds were able to distinguish two alpha(1)-adrenoceptor subtypes in the epididymal tissue, as revealed by the discontinuity of their inhibition curves. A mean ratio of 24:76 for these alpha(1)-adrenoceptors was determined from compounds 8-10, 12, and 15-17. Furthermore, compounds 9, 10, 12, 16a, and 16b showed higher affinity towards the minor population of receptors, whereas compounds 8, 15, and 17 preferentially inhibited the major population of alpha(1)-adrenoceptors. In addition, selected pharmacological experiments demonstrated the complementary antagonism of the two series of compounds and their different, preferential affinity for one of the two alpha(1)-adrenoceptor subtypes. In conclusion, we found beta-chloroethylamines that demonstrate a multiplicity of alpha(1)-adrenoceptors in the epididymal portion of young CD rat vas deferens and, as a consequence, they are possible useful tools for alpha(1)-adrenoceptor characterization. (C) 2002 Elsevier Science Ltd. All rights reserved.