2-[2-(4-Benzyl-phenoxy)-ethyl]-isoindole-1,3-dione | 302962-75-0

• 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-(4-Benzyl-phenoxy)-ethyl]-isoindole-1,3-dione
• 英文别名: 2-[2-(4-Benzylphenoxy)ethyl]isoindole-1,3-dione
• CAS: 302962-75-0
• 化学式: C₂₃H₁₉NO₃
• 分子量: 357.409
• InChiKey: GYIQMMOSMLAKNV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[2-(4-Benzyl-phenoxy)-ethyl]-isoindole-1,3-dione 在 一水合肼 、 盐酸 作用下， 以 乙醇 为溶剂， 反应 3.5h， 以81%的产率得到2-[4-(phenylmethyl)phenoxy]ethanamine hydrochloride
  参考文献：
  名称：

  Synthesis, binding and structure–affinity studies of new ligands for the microsomal anti-estrogen binding site (AEBS)

  摘要：

  New compounds have been synthesized based on the structure of the anti-tumoral drug tamoxifen and its diphenylmethane derivative, N,N-diethyl-2-[(4-phenyl-methyl)-phenoxy]-ethanamine HCl (DPPE). These new compounds have no affinity for the estrogen receptor (ER) and bind with various affinity to the anti-estrogen binding site (AEBS). Compounds 2, 10, 12, 13, 20a, 20b, 23a, 23b, 29 exhibited 1.1- 69.5 higher affinity than DPPE, and compounds 23a and 23b have 1.2 and 3.5 higher affinity than tamoxifen. Three-dimensional structure analysis, performed using the intersection of the van der Waals volume occupied by tamoxifen in its crystallographic state and the van der Waals volume of these new compounds in their calculated minimal energy conformation, correlated well with their pki for AEBS (r = 0.84, P < 0.0001, n = 18). This is the first structure-affinity relationship (SAR) ever reported for AEBS ligands. Moreover in this study we have reported the synthesis of new compounds of higher affinity than the lead compounds and that are highly specific for AEBS. Since these compounds do not bind ER they will be helpful to study AEBS mediated cytotoxicity. Moreover our study shows that our strategy is a new useful guide to design high affinity and selective ligands for AEBS. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00119-x
• 作为产物：
  描述：

  4-羟基二苯甲烷 在 四溴化碳 、 potassium carbonate 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 32.0h， 生成 2-[2-(4-Benzyl-phenoxy)-ethyl]-isoindole-1,3-dione
  参考文献：
  名称：

  Synthesis, binding and structure–affinity studies of new ligands for the microsomal anti-estrogen binding site (AEBS)

  摘要：

  New compounds have been synthesized based on the structure of the anti-tumoral drug tamoxifen and its diphenylmethane derivative, N,N-diethyl-2-[(4-phenyl-methyl)-phenoxy]-ethanamine HCl (DPPE). These new compounds have no affinity for the estrogen receptor (ER) and bind with various affinity to the anti-estrogen binding site (AEBS). Compounds 2, 10, 12, 13, 20a, 20b, 23a, 23b, 29 exhibited 1.1- 69.5 higher affinity than DPPE, and compounds 23a and 23b have 1.2 and 3.5 higher affinity than tamoxifen. Three-dimensional structure analysis, performed using the intersection of the van der Waals volume occupied by tamoxifen in its crystallographic state and the van der Waals volume of these new compounds in their calculated minimal energy conformation, correlated well with their pki for AEBS (r = 0.84, P < 0.0001, n = 18). This is the first structure-affinity relationship (SAR) ever reported for AEBS ligands. Moreover in this study we have reported the synthesis of new compounds of higher affinity than the lead compounds and that are highly specific for AEBS. Since these compounds do not bind ER they will be helpful to study AEBS mediated cytotoxicity. Moreover our study shows that our strategy is a new useful guide to design high affinity and selective ligands for AEBS. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00119-x

文献信息

• Synthesis, binding and structure–affinity studies of new ligands for the microsomal anti-estrogen binding site (AEBS)
  作者：Marc Poirot、Philippe De Medina、Frederic Delarue、Jean-Jacques Perie、Alain Klaebe、Jean-Charles Faye

  DOI：10.1016/s0968-0896(00)00119-x

  日期：2000.8

  New compounds have been synthesized based on the structure of the anti-tumoral drug tamoxifen and its diphenylmethane derivative, N,N-diethyl-2-[(4-phenyl-methyl)-phenoxy]-ethanamine HCl (DPPE). These new compounds have no affinity for the estrogen receptor (ER) and bind with various affinity to the anti-estrogen binding site (AEBS). Compounds 2, 10, 12, 13, 20a, 20b, 23a, 23b, 29 exhibited 1.1- 69.5 higher affinity than DPPE, and compounds 23a and 23b have 1.2 and 3.5 higher affinity than tamoxifen. Three-dimensional structure analysis, performed using the intersection of the van der Waals volume occupied by tamoxifen in its crystallographic state and the van der Waals volume of these new compounds in their calculated minimal energy conformation, correlated well with their pki for AEBS (r = 0.84, P < 0.0001, n = 18). This is the first structure-affinity relationship (SAR) ever reported for AEBS ligands. Moreover in this study we have reported the synthesis of new compounds of higher affinity than the lead compounds and that are highly specific for AEBS. Since these compounds do not bind ER they will be helpful to study AEBS mediated cytotoxicity. Moreover our study shows that our strategy is a new useful guide to design high affinity and selective ligands for AEBS. (C) 2000 Elsevier Science Ltd. All rights reserved.