N-butyl-N-methyl-5,6-bis(4'-methoxyphenyl)-4-thiahexanamide

• 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: N-butyl-N-methyl-5,6-bis(4'-methoxyphenyl)-4-thiahexanamide
• 英文别名: 3-[1,2-bis(4-methoxyphenyl)ethylsulfanyl]-N-butyl-N-methylpropanamide
• 化学式: C₂₄H₃₃NO₃S
• 分子量: 415.597
• InChiKey: WFWABMOYBVSPBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  64.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,2-bis(4-methoxyphenyl)ethan-1-ol 在 氢氧化钾 、 三正丁胺 、 zinc(II) chloride 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 10.5h， 生成 N-butyl-N-methyl-5,6-bis(4'-methoxyphenyl)-4-thiahexanamide
  参考文献：
  名称：

  Synthesis and Antiestrogenic Activity of Diaryl Thioether Derivatives

  摘要：

  The reaction of 1,2-diarylethanol and mercapto side chain catalyzed by ZnI2 was used as a key step in the short (three to five steps) and efficient synthesis of 17 diaryl thioether derivatives. Several of these compounds contain a methyl butyl amide chain and an hydroxyaryl moiety, respectively, for antiestrogenic activity and binding affinity on estrogen receptor. No binding affinity for crude cytosolic preparation of the estrogen receptor was observed for compounds without phenolic group, while a low affinity (0.01-0.05%) was measured for mono- or diphenol derivatives. Like the pure steroidal antiestrogen EM-139, these novel nonsteroidal compounds did not exert any stimulatory effect on cell proliferation of (ER(+)) ZR-75-1 human breast cancer cells and partially reversed the amplitude of the stimulatory effect induced by estradiol on this (ER(+)) cell line. No proliferative or antiproliferative effect on (ER(-)) MDA-MB-231 human breast cancer cells was also observed for three of these compounds (39-41). Among the newly synthesized nonsteroidal compounds, the thioether derivative 41 (N-butyl-N-methyl-13,14-bis(4'-hydroxyphenyl)-12-thiatetradecanamide), with a long methylbutylalkanamide side chain and a diphenolic nucleus, was selected as the best antiestrogenic compound. However;this compound was 100-fold less antiestrogenic in (ER(+)) ZR-75-1 cells than the steroidal antiestrogen EM-139.

  DOI：

  10.1021/jm00034a009

文献信息

• Synthesis and Antiestrogenic Activity of Diaryl Thioether Derivatives
  作者：Donald Poirier、Serge Auger、Yves Merand、Jacques Simard、Fernand Labrie

  DOI：10.1021/jm00034a009

  日期：1994.4

  The reaction of 1,2-diarylethanol and mercapto side chain catalyzed by ZnI2 was used as a key step in the short (three to five steps) and efficient synthesis of 17 diaryl thioether derivatives. Several of these compounds contain a methyl butyl amide chain and an hydroxyaryl moiety, respectively, for antiestrogenic activity and binding affinity on estrogen receptor. No binding affinity for crude cytosolic preparation of the estrogen receptor was observed for compounds without phenolic group, while a low affinity (0.01-0.05%) was measured for mono- or diphenol derivatives. Like the pure steroidal antiestrogen EM-139, these novel nonsteroidal compounds did not exert any stimulatory effect on cell proliferation of (ER(+)) ZR-75-1 human breast cancer cells and partially reversed the amplitude of the stimulatory effect induced by estradiol on this (ER(+)) cell line. No proliferative or antiproliferative effect on (ER(-)) MDA-MB-231 human breast cancer cells was also observed for three of these compounds (39-41). Among the newly synthesized nonsteroidal compounds, the thioether derivative 41 (N-butyl-N-methyl-13,14-bis(4'-hydroxyphenyl)-12-thiatetradecanamide), with a long methylbutylalkanamide side chain and a diphenolic nucleus, was selected as the best antiestrogenic compound. However;this compound was 100-fold less antiestrogenic in (ER(+)) ZR-75-1 cells than the steroidal antiestrogen EM-139.