(S,Z)-4-(5-hydroxy-1-(4-((1-methylpyrrolidin-2-yl)methoxy)phenyl)-2-phenylpent-1-en-1-yl)phenol hydrochloride salt

• 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: (S,Z)-4-(5-hydroxy-1-(4-((1-methylpyrrolidin-2-yl)methoxy)phenyl)-2-phenylpent-1-en-1-yl)phenol hydrochloride salt
• 英文别名: 4-[(Z)-5-hydroxy-1-[4-[[(2S)-1-methylpyrrolidin-2-yl]methoxy]phenyl]-2-phenylpent-1-enyl]phenol;hydrochloride
• 化学式: C₂₉H₃₃NO₃*ClH
• 分子量: 480.047
• InChiKey: OCAIWVBOBFRZBY-CJGRHYNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.02
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  52.9
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S,E)-methyl 5-(4-((1-methylpyrrolidin-2-yl)methoxy)phenyl)-4-phenyl-5-(4-(pivaloyloxy)phenyl)pent-4-enoate 在 lithium aluminium tetrahydride 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 0.17h， 以4%的产率得到(S,Z)-4-(5-hydroxy-1-(4-((1-methylpyrrolidin-2-yl)methoxy)phenyl)-2-phenylpent-1-en-1-yl)phenol hydrochloride salt
  参考文献：
  名称：

  Insights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists

  摘要：

  We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERR gamma but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERR gamma over the ERR alpha, -beta, and ER alpha. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b-possess advantageous druglike properties and can be used to potentially treat various ERR gamma-related disorders.

  DOI：

  10.1021/acs.jmedchem.6b01204

文献信息

• Insights of a Lead Optimization Study and Biological Evaluation of Novel 4-Hydroxytamoxifen Analogs as Estrogen-Related Receptor γ (ERRγ) Inverse Agonists
  作者：Jina Kim、Seo Yeon Woo、Chun Young Im、Eun Kyung Yoo、Seungmi Lee、Hyo-Ji Kim、Hee-Jong Hwang、Joong-heui Cho、Won Seok Lee、Heeseok Yoon、Shinae Kim、Oh-bin Kwon、Hayoung Hwang、Kyung-Hee Kim、Jae-Han Jeon、Thoudam Debraj Singh、Sang Wook Kim、Sung Yeoun Hwang、Hueng-Sik Choi、In-Kyu Lee、Seong Heon Kim、Yong Hyun Jeon、Jungwook Chin、Sung Jin Cho

  DOI：10.1021/acs.jmedchem.6b01204

  日期：2016.11.23

  We evaluated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that not only were shown to be highly selective agonists for ERR gamma but also exhibited enhanced pharmacokinetic profile compared with 3 (GSK5182). 6g and 10b had comparable potency to 3 and were far more selective for ERR gamma over the ERR alpha, -beta, and ER alpha. The in vivo pharmacokinetic profiles of 6g and 10b were further evaluated, as they possessed superior in vitro ADMET profiles compared to the other compounds. Additionally, we observed a significant increase of fully glycosylated NIS protein, key protein for radioiodine therapy in anaplastic thyroid cancer (ATC), in 6g- or 10b treated CAL62 cells, which indicated that these compounds could be promising enhancers for restoring NIS protein function in ATC cells. Thus, 6g and 10b-possess advantageous druglike properties and can be used to potentially treat various ERR gamma-related disorders.