(Z)-1-<4-(2-chloroethoxy)phenyl>-1-(4-n-butylphenyl)-2-phenyl-1-butene | 160465-87-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (Z)-1-<4-(2-chloroethoxy)phenyl>-1-(4-n-butylphenyl)-2-phenyl-1-butene
• 英文别名: 1-butyl-4-[(Z)-1-[4-(2-chloroethoxy)phenyl]-2-phenylbut-1-enyl]benzene
• CAS: 160465-87-2
• 化学式: C₂₈H₃₁ClO
• 分子量: 419.007
• InChiKey: UXNJTWDURRCJCD-DQSJHHFOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.6
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  四氢吡咯 、 (Z)-1-<4-(2-chloroethoxy)phenyl>-1-(4-n-butylphenyl)-2-phenyl-1-butene 以 乙醇 为溶剂， 反应 3.0h， 以52%的产率得到1-(2-{4-[(Z)-1-(4-Butyl-phenyl)-2-phenyl-but-1-enyl]-phenoxy}-ethyl)-pyrrolidine
  参考文献：
  名称：

  Rationally Designed Analogs of Tamoxifen with Improved Calmodulin Antagonism

  摘要：

  Computerized molecular modeling studies on the interactions of the antiestrogen tamoxifen (1) and its analogues bound to the calcium-binding protein calmodulin have guided the rational design of more potent antagonists. Compounds with either three or four methylene units in the basic side chain or slim lipophilic 4-substituents were expected to be more potent. All compounds were tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to the estrogen receptor from rat uteri. Some compounds were assayed for cytotoxicity against MCF-7 breast tumor cells in vitro. Introduction of lipophilic 4-substituents was accomplished by using palladium(0)-catalyzed coupling reactions with a 4-iodinated precursor. Both the 4-ethynyl (16 and 17) and 4-butyl (18 and 19) compounds were more potent calmodulin antagonists than tamoxifen. Extension of the basic aminoethoxy side chain of 4-iodotamoxifen (3) and idoxifene (2) ((E)-1-[4-[2-(N-pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene) by one or two methylene units resulted in modest gains in calmodulin antagonism (10-13). All the compounds assayed retained estrogen receptor binding characteristics. The compound possessing the optimal combination of calmodulin antagonism and estrogen receptor binding was 12 ((E)-1-[4-[3-(N-pyrrolidino)propoxy]phen 1-(4-iodophenyl)-2-phenyl-1-butene) (IC50 = 1.1 mu M, RBA = 23). Correlation between calmodulin antagonism and cytotoxicity was demonstrated for selected compounds.'

  DOI：

  10.1021/jm00002a005
• 作为产物：
  描述：

  正丁基锂 、 (E)-1-<4-(2-chloroethoxy)phenyl>-1-(4-iodophenyl)-2-phenyl-1-butene 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 zinc(II) chloride 作用下， 以 乙醚 、 正己烷 为溶剂， 以80%的产率得到(Z)-1-<4-(2-chloroethoxy)phenyl>-1-(4-n-butylphenyl)-2-phenyl-1-butene
  参考文献：
  名称：

  Rationally Designed Analogs of Tamoxifen with Improved Calmodulin Antagonism

  摘要：

  Computerized molecular modeling studies on the interactions of the antiestrogen tamoxifen (1) and its analogues bound to the calcium-binding protein calmodulin have guided the rational design of more potent antagonists. Compounds with either three or four methylene units in the basic side chain or slim lipophilic 4-substituents were expected to be more potent. All compounds were tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to the estrogen receptor from rat uteri. Some compounds were assayed for cytotoxicity against MCF-7 breast tumor cells in vitro. Introduction of lipophilic 4-substituents was accomplished by using palladium(0)-catalyzed coupling reactions with a 4-iodinated precursor. Both the 4-ethynyl (16 and 17) and 4-butyl (18 and 19) compounds were more potent calmodulin antagonists than tamoxifen. Extension of the basic aminoethoxy side chain of 4-iodotamoxifen (3) and idoxifene (2) ((E)-1-[4-[2-(N-pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene) by one or two methylene units resulted in modest gains in calmodulin antagonism (10-13). All the compounds assayed retained estrogen receptor binding characteristics. The compound possessing the optimal combination of calmodulin antagonism and estrogen receptor binding was 12 ((E)-1-[4-[3-(N-pyrrolidino)propoxy]phen 1-(4-iodophenyl)-2-phenyl-1-butene) (IC50 = 1.1 mu M, RBA = 23). Correlation between calmodulin antagonism and cytotoxicity was demonstrated for selected compounds.'

  DOI：

  10.1021/jm00002a005

文献信息

• Rationally Designed Analogs of Tamoxifen with Improved Calmodulin Antagonism
  作者：Ian R. Hardcastle、Martin G. Rowlands、John Houghton、Iris B. Parr、Gerard A. Potter、Michael Jarman、Karen J. Edwards、Charles A. Laughton、John O. Trent、Stephen Neidle

  DOI：10.1021/jm00002a005

  日期：1995.1

  Computerized molecular modeling studies on the interactions of the antiestrogen tamoxifen (1) and its analogues bound to the calcium-binding protein calmodulin have guided the rational design of more potent antagonists. Compounds with either three or four methylene units in the basic side chain or slim lipophilic 4-substituents were expected to be more potent. All compounds were tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to the estrogen receptor from rat uteri. Some compounds were assayed for cytotoxicity against MCF-7 breast tumor cells in vitro. Introduction of lipophilic 4-substituents was accomplished by using palladium(0)-catalyzed coupling reactions with a 4-iodinated precursor. Both the 4-ethynyl (16 and 17) and 4-butyl (18 and 19) compounds were more potent calmodulin antagonists than tamoxifen. Extension of the basic aminoethoxy side chain of 4-iodotamoxifen (3) and idoxifene (2) ((E)-1-[4-[2-(N-pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene) by one or two methylene units resulted in modest gains in calmodulin antagonism (10-13). All the compounds assayed retained estrogen receptor binding characteristics. The compound possessing the optimal combination of calmodulin antagonism and estrogen receptor binding was 12 ((E)-1-[4-[3-(N-pyrrolidino)propoxy]phen 1-(4-iodophenyl)-2-phenyl-1-butene) (IC50 = 1.1 mu M, RBA = 23). Correlation between calmodulin antagonism and cytotoxicity was demonstrated for selected compounds.'