4-[6-methoxy-2-(4-chlorophenyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl]phenol | 645393-91-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 4-[6-methoxy-2-(4-chlorophenyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl]phenol
• 英文别名: 4-[2-(4-Chlorophenyl)-6-methoxy-1-methyl-3,4-dihydroisoquinolin-1-yl]phenol
• CAS: 645393-91-5
• 化学式: C₂₃H₂₂ClNO₂
• 分子量: 379.886
• InChiKey: SYRDPZFWQIIENF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 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：

  4-[6-methoxy-2-(4-chlorophenyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl]phenol 在 三氯化铝 、 sodium hydride 、 乙硫醇 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 生成 2-(4-Chloro-phenyl)-1-methyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-1,2,3,4-tetrahydro-isoquinolin-6-ol
  参考文献：
  名称：

  Estrogen Receptor Modulators:  Identification and Structure−Activity Relationships of Potent ERα-Selective Tetrahydroisoquinoline Ligands

  摘要：

  As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), tetrahydroisoquinoline derivative 27 was discovered by high throughput screening. Successive replacements of the p-F substituent of 27 by an aminoethoxy side chain and of the 1-H of the tetrahydroisoquinoline core by a 1-Me group provided analogues 19 and 20. These compounds showed potencies in a cell-based reporter gene assay (ERE assay) varying between 0.6 and 20 nM and displayed antagonist behaviors in the MCF-7 human breast adenocarcinoma cell line with IC(50)s in the range of 2-36 nM. The effect of N-phenyl substituents on the activity and pharmacokinetic properties of tetrahydroisoquinoline analogues was explored. As a result of this investigation, two potent derivatives bearing a p-F N-aryl group, 19c and 20c, were discovered as candidates suitable for further profiling. To gain insight into the ligand-receptor interaction, the X-ray crystallographic structure of the 1-H tetrahydroisoquinoline derivative (R)-18a in complex with ERalpha-ligand binding domain (LBD)(301-553)/C-->S triple mutant was solved to 2.28 Angstrom. An overlay of this X-ray crystal structure with that reported for the complex of ERalpha-LBD301-553/carboxymethylated C and raloxifene (5) shows that both compounds bind to the same cleft of the receptor and display comparable binding modes, with differences being observed in the conformation of their "D-ring" phenyl groups.

  DOI：

  10.1021/jm030086h
• 作为产物：
  描述：

  6-甲氧基-3,4-二氢-1(2H)-异喹啉 在 copper(l) iodide 、 三氯化铝 、 potassium carbonate 、 N,N-二甲基苯胺 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成 4-[6-methoxy-2-(4-chlorophenyl)-1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl]phenol
  参考文献：
  名称：

  Estrogen Receptor Modulators:  Identification and Structure−Activity Relationships of Potent ERα-Selective Tetrahydroisoquinoline Ligands

  摘要：

  As part of a program aimed at the development of selective estrogen receptor modulators (SERMs), tetrahydroisoquinoline derivative 27 was discovered by high throughput screening. Successive replacements of the p-F substituent of 27 by an aminoethoxy side chain and of the 1-H of the tetrahydroisoquinoline core by a 1-Me group provided analogues 19 and 20. These compounds showed potencies in a cell-based reporter gene assay (ERE assay) varying between 0.6 and 20 nM and displayed antagonist behaviors in the MCF-7 human breast adenocarcinoma cell line with IC(50)s in the range of 2-36 nM. The effect of N-phenyl substituents on the activity and pharmacokinetic properties of tetrahydroisoquinoline analogues was explored. As a result of this investigation, two potent derivatives bearing a p-F N-aryl group, 19c and 20c, were discovered as candidates suitable for further profiling. To gain insight into the ligand-receptor interaction, the X-ray crystallographic structure of the 1-H tetrahydroisoquinoline derivative (R)-18a in complex with ERalpha-ligand binding domain (LBD)(301-553)/C-->S triple mutant was solved to 2.28 Angstrom. An overlay of this X-ray crystal structure with that reported for the complex of ERalpha-LBD301-553/carboxymethylated C and raloxifene (5) shows that both compounds bind to the same cleft of the receptor and display comparable binding modes, with differences being observed in the conformation of their "D-ring" phenyl groups.

  DOI：

  10.1021/jm030086h

文献信息

• Synthesis and preliminary biological evaluation of new carbon-11 labeled tetrahydroisoquinoline derivatives as SERM radioligands for PET imaging of ER expression in breast cancer
  作者：Mingzhang Gao、Min Wang、Kathy D. Miller、George W. Sledge、Qi-Huang Zheng

  DOI：10.1016/j.ejmech.2008.01.001

  日期：2008.10

  receptor-based breast cancer imaging agents for diagnostic use in biomedical imaging technique positron emission tomography (PET). Tetrahydroisoquinoline derivatives are a class of selective estrogen receptor modulators (SERMs) with high binding affinity and specificity exhibiting up to 50 folds for ERalpha over ERbeta. New carbon-11 labeled tetrahydroisoquinoline derivatives, [11C]methyl 1-(2-(4-(2-(4-f

  雌激素受体（ERs）是治疗乳腺癌和开发基于受体的乳腺癌显像剂的诱人靶标，可用于生物医学成像技术正电子发射断层扫描（PET）的诊断。四氢异喹啉衍生物是一类选择性雌激素受体调节剂（SERM），具有较高的结合亲和力和特异性，相对于ERbeta，其对ERalpha的表达高达50倍。新的碳11标记的四氢异喹啉衍生物，[11C]甲基1-（2-（4-（2-（4-氟苯基）-6-羟基-1-甲基-1,2,3,4-四氢异喹啉-1-基）苯氧基）乙基）哌啶-4-羧酸酯（[11C] 10a）和[11C]甲基1-（2-（4-（2-（4-（4-氯苯基）-6-羟基-1-甲基-1,2）首先设计，合成和评估了3,4-四氢异喹啉-1-基）苯氧基）乙基）哌啶-4-羧酸酯（[11C] 10b）。使用[11C] CH3OTf通过对其相应前体进行O- [11C]甲基化来制备目标示踪剂，并通过固相萃取（SPE）纯化程序进行分离，以40-6