trans-(Z)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-1,2-diphenyl-1-penten-5-ol | 97151-05-8

• 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: trans-(Z)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-1,2-diphenyl-1-penten-5-ol
• 英文别名: Benzenebutanol, I-[[4-[2-(dimethylamino)ethoxy]phenyl]phenylmethylene]-, (Z)-；(Z)-5-[4-[2-(dimethylamino)ethoxy]phenyl]-4,5-diphenylpent-4-en-1-ol
• CAS: 97151-05-8
• 化学式: C₂₇H₃₁NO₂
• 分子量: 401.549
• InChiKey: DPYXJKGMJLNRNX-RQZHXJHFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 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：

  trans-(Z)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-1,2-diphenyl-1-penten-5-ol 在 盐酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 0.17h， 以6.8 mg的产率得到(Z)-5-(4-(2-(dimethylamino)ethoxy)phenyl)-4,5-diphenylpent-4-en-1-ol hydrochloride
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 4-hydroxytamoxifen analogs as estrogen-related receptor gamma inverse agonists

  摘要：

  Estrogen-related receptor gamma (ERRγ) has recently been recognized as an attractive target for treating inflammation, cancer, and metabolic disorders. Herein, we discovered and demonstrated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that could act as highly selective inverse agonists for ERRγ. The results were comparable to those for GSK5182 (4), a leading ERRγ inverse agonist ligand. Briefly, the half-maximal inhibitory concentration (IC50) range of the synthesized compounds for ERRγ was 0.1-10 μM. Impressively, compound 24e exhibited potency comparable to 4 but was more selective for ERRγ over three other subtypes: ERRα, ERRβ, and estrogen receptor α. Furthermore, compound 24e exhibited a superior in vitro ADMET profile compared to the other compounds. Thus, the newly synthesized class of ERRγ inverse agonists could be lead candidates for developing clinical therapies for ERRγ-related disorders.

  DOI：

  10.1016/j.ejmech.2016.04.076
• 作为产物：
  描述：

  4-羟基苯基-(4-溴-苯基)-甲酮 在 lithium aluminium tetrahydride 、 四氯化钛 、 potassium carbonate 、 锌 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 5.0h， 生成 trans-(Z)-1-{4-[2-(dimethylamino)ethoxy]phenyl}-1,2-diphenyl-1-penten-5-ol
  参考文献：
  名称：

  Synthesis and biological evaluation of novel 4-hydroxytamoxifen analogs as estrogen-related receptor gamma inverse agonists

  摘要：

  Estrogen-related receptor gamma (ERRγ) has recently been recognized as an attractive target for treating inflammation, cancer, and metabolic disorders. Herein, we discovered and demonstrated the in vitro pharmacology as well as the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of chemical entities that could act as highly selective inverse agonists for ERRγ. The results were comparable to those for GSK5182 (4), a leading ERRγ inverse agonist ligand. Briefly, the half-maximal inhibitory concentration (IC50) range of the synthesized compounds for ERRγ was 0.1-10 μM. Impressively, compound 24e exhibited potency comparable to 4 but was more selective for ERRγ over three other subtypes: ERRα, ERRβ, and estrogen receptor α. Furthermore, compound 24e exhibited a superior in vitro ADMET profile compared to the other compounds. Thus, the newly synthesized class of ERRγ inverse agonists could be lead candidates for developing clinical therapies for ERRγ-related disorders.

  DOI：

  10.1016/j.ejmech.2016.04.076

文献信息

• Hydroxy derivatives of tamoxifen
  作者：Allan B. Foster、Michael Jarman、On Tai Leung、Raymond McCague、Guy Leclercq、N. Devleeschouwer

  DOI：10.1021/jm00148a020

  日期：1985.10

  contrast to the known 3- and 4-hydroxy derivatives which were obtained as near-equimolar cis,trans mixtures, only the trans forms of the 2-hydroxy, 2-methyl, 2,4-dihydroxy, and 4-hydroxy-2-methyl derivatives were obtained. Also, in contrast to the trans forms of the 3- and 4-hydroxy derivatives, which are readily equilibrated to cis,trans mixtures, the trans 2-hydroxy derivative could not be isomerized

  在探索影响他莫昔芬[反-（Z）-1- [4- [2-（二甲基氨基）乙氧基] RBA（相对于雌二醇的大鼠子宫雌激素受体的结合亲和力）的结构特征苯基] -1,2，2-二苯基-1-丁烯]系列，已经合成了在1-苯基上被各种取代的几种衍生物。[在他莫昔芬系列中，定义几何异构体的构型并取决于芳族部分和乙基中取代基的位置和性质的描述符E和Z可能会有所变化，尽管相对构型（顺式或反式）才不是。为了避免混淆，在本文中将使用术语顺式和反式来表示4- [2-（二甲基氨基）乙氧基]苯基与乙基（或羟乙基，羟丙基，每一合成的最后阶段涉及叔醇的酸催化脱水，与已知的近似等摩尔顺式的3-和4-羟基衍生物相反，反式混合物，仅获得2-羟基，2-甲基，2，4-二羟基和4-羟基-2-甲基衍生物的反式形式。同样，与3-和4-羟基衍生物的反式形式很容易平衡成顺式，反式混合物相反，反式2-羟基衍生物不能被异构化。他莫昔芬和2-甲基他莫昔芬