2-[4-(4-甲氧基-alpha-苯基苯乙基)苯氧基]乙基二乙胺 | 6732-77-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 2-[4-(4-甲氧基-alpha-苯基苯乙基)苯氧基]乙基二乙胺
• 英文名称: 1-<4-(2-dietylaminoethoxy)phenyl>-1-phenyl-2-<4-methoxyphenyl>ethane
• 英文别名: 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenyl ethane；1-<4-(2-Diaethylamino-aethoxy)-phenyl>-2-<4-methoxy-phenyl>-1-phenyl-aethan；1-(p-(beta-Diethylaminoethoxy)phenyl)-1-phenyl-2-(p-methoxyphenyl)ethane；N,N-diethyl-2-[4-[2-(4-methoxyphenyl)-1-phenylethyl]phenoxy]ethanamine
• CAS: 6732-77-0
• 化学式: C₂₇H₃₃NO₂
• 分子量: 403.565
• InChiKey: OOKFERAEMXLNEU-UHFFFAOYSA-N

物化性质

• 沸点：
  525.41°C (rough estimate)
• 密度：
  1.0774 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  30
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  21.7
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2922299090

反应信息

• 作为产物：
  描述：

  对甲氧基苯乙酸 在 palladium on activated charcoal 氢气 、 对甲苯磺酸 、 二乙胺 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 乙醚 、 氯仿 、 异丙醇 、 乙腈 、 苯 为溶剂， 反应 106.0h， 生成 2-[4-(4-甲氧基-alpha-苯基苯乙基)苯氧基]乙基二乙胺
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Cyclopropyl Analogs of the Antiestrogen MER 25

  摘要：

  In an effort to prepare effective nonsteroidal antiestrogens without intrinsic estrogenicity and with greater antagonism than the triarylethylenes (tamoxifen), four (E)- and (Z)-1,1-dichloro-2-phenyl-2-[4-(2-diethylaminoethoxy) phenyl]-3-(4-methoxyphenyl)cyclopropane analogs of the antiestrogen MER 25, of which two of the compounds had a 4-heptafluorotolyl group in the ct-ring, were prepared. The (E)- and (Z)-gem-dichlorotriarylcyclopropanes were tested for their ability to inhibit the growth of estrogen receptor (ER)-positive MCF-7E3 and ER-negative MDA-MB-231 human breast cancer cells in culture. All compounds, except 18E, exhibited a statistically significant (P < 0.01) reduction in estradiol-stimulated growth (antiestrogenic activity) at 1.0 mu M concentration in the MCF-7E3 cells: 11Z (88%), 11E (106%), 18Z (65%), and the test compounds 7A(Z) (85%), 7A(E) (53%), MRL 37 (91%), MER 25 (71%), and ICI 182,780 (102%). Inhibition of estradiol-stimulated growth at concentrations lower than 1.0 mu M was demonstrated by 11E, MER 25, and ICI 182,780. Compound 11E produced weak inhibition at 0.1 nM (19%) and nearly complete inhibition (79-112%) over a concentration range of 1.0 to 100 nM. MER 25 produced inhibition of estradiol-stimulated growth at 1.0 (39%), 10 (102%), and 100 nM (100%) concentrations. ICI 182,780 completely inhibited estrogen-stimulated growth from 0.1 nM to 1.0 mu M concentrations. Two compounds exhibited estrogenic activity: 18E (from 1.0 nM to 1.0 mu M concentrations) and MER 25, which had antiestrogenic action at the lower concentration ranges, but exhibited estrogenic properties at 100 nM to 1.0 mu M concentrations. None of the test compounds or standards were active in the MDA-MB-231 cell line at the concentrations studied (0.01 nM to 1.0 mu M). In addition, none of the compounds inhibited cell growth below control in the MCF-7E3 cell line. The results from both cell lines suggest that the test compounds are devoid of any antitumor properties, which is thought to be mediated through a nonreceptor mechanism. Analog 11E has the potential to be useful in the treatment of hormone-responsive breast cancer. (C) 1998 Academic Press.

  DOI：

  10.1006/bioo.1998.1081

文献信息

• Prevention and treatment of cardiovascular pathologies with tamoxifen analogues
  申请人：Poniard Pharmaceuticals, Inc.

  公开号：EP1980246A1

  公开（公告）日：2008-10-15

  Use is provided of a compound of formula (I): wherein Z is C=O or a covalent bond; Y is H or O(C1-C4)alkyl, R1 and R2 are individually (C1-C4)alkyl or together with N are a saturated heterocyclic group, R3 is ethyl or chloroethyl, R4 is H or together with R3 is -CH2-CH2- or -S-, R5 is O(C1-C4)alkyl or H and R6 is O(C1-C4)alkyl or H with the proviso that when R4, R5, and R6 are H, R3 is not ethyl; or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for use in: the treatment or prevention of cardiovascular pathologies e.g. atherosclerosis, thrombosis, myocardial infarction or stroke, inhibiting smooth muscle cell (SMC) proliferation associated with procedural vascular trauma, preventing or treating a cardiovascular or vascular indication in a mammal characterised by a decreased lumen diameter, or increasing the level of TGF-beta in a mammal, effective to elevate the level of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke. Useful compounds include idoxifene, toremifene or salts thereof. Further provided is a method for identifying an agent that elevates the level of TGF beta. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifen or structural analogs thereof, including compounds of formula (1).

  提供了式 (I) 化合物的用途： 其中 Z 是 C=O 或共价键； Y 是 H 或 O（C1-C4）烷基、 R1 和 R2 单独为 (C1-C4) 烷基或与 N 一起为饱和杂环基团、 R3 是乙基或氯乙基、 R4 是 H 或与 R3 一起是-CH2-CH2-或-S-，R5 是 O（C1-C4）烷基或 H，R6 是 O（C1-C4）烷基或 H，但当 R4、R5 和 R6 是 H 时，R3 不是乙基； 或其药学上可接受的盐，用于制造以下用途的药物治疗或预防心血管病变，如动脉粥样硬化、血栓形成、心肌梗塞或中风；抑制与程序性血管创伤相关的平滑肌细胞（SMC）增殖；预防或治疗哺乳动物以管腔直径减小为特征的心血管或血管适应症；或提高哺乳动物体内 TGF-beta 的水平，有效提高 TGF-beta 的水平以治疗和/或预防动脉粥样硬化、血栓形成、心肌梗塞和中风等疾病。有用的化合物包括依多昔芬、托瑞米芬或其盐类。本发明还提供了一种鉴定可提高 TGF beta 水平的制剂的方法。本发明的另一个实施方案是一种测定体外 TGF-beta 的检测方法或试剂盒。本发明还提供了一种治疗方法，包括通过施用他莫昔芬或其结构类似物（包括式（1）化合物）来抑制与程序性血管创伤相关的平滑肌细胞增殖。
• Method to determine TGF-beta
  申请人：NeoRx Corporation

  公开号：US20020182659A1

  公开（公告）日：2002-12-05

  A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (1): 1 wherein Z is C═O or a covalent bond; Y is H or O(C 1 -C 4 )alkyl, R 1 and R 2 are individually (C 1 -C 4 )alkyl or together with N are a saturated heterocyclic group, R 3 is ethyl or chloroethyl, R 4 is H or together with R 3 is —CH 2 CH 2 — or —S—, R 5 is I, O(C 1 -C 4 )alkyl or H, and R 6 is I, O(C 1 -C 4 )alkyl or H with the proviso that when R 4 , R 5 , and R 6 are H, R 3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to activate or stimulate production of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene and salts thereof. Further provided is a method for identifying a compound that is a TGF-beta activator or production stimulator is provided. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifen or structural analogs thereof, including compounds of formula (I).

  一种通过施用式（1）化合物治疗或预防心血管疾病的方法： 1 其中 Z 是 C&boxH；O 或共价键；Y 是 H 或 O(C 1 -C 4 )烷基，R 1 和 R 2 分别是（C 1 -C 4 )烷基或与 N 一起为饱和杂环基团，R 3 是乙基或氯乙基，R 4 是 H 或与 R 3 是-CH 2 CH 2 - 或-S-，R 5 是 I、O(C 1 -C 4 烷基或 H，而 R 6 是 I、O（C 1 -C 4 烷基或 H，但当 R 4 , R 5 和 R 6 为 H，R 3 不是乙基；或其药学上可接受的盐，可有效激活或刺激 TGF-beta 的产生，从而治疗和/或预防动脉粥样硬化、血栓形成、心肌梗塞和中风等疾病。有用的化合物包括艾多昔芬及其盐类。本发明还提供了一种用于鉴定 TGF-beta 激活剂或生成刺激剂的化合物的方法。本发明的另一个实施方案是一种测定体外 TGF-beta 的检测方法或试剂盒。本发明还提供了一种治疗方法，包括通过施用他莫昔芬或其结构类似物（包括式 (I) 化合物）来抑制与程序性血管创伤相关的平滑肌细胞增殖。
• Compounds and therapies for the prevention of vascular and non-vascular pathologies
  申请人：NeoRx Corporation

  公开号：US20030064970A1

  公开（公告）日：2003-04-03

  The invention provides a method of treating a mammal having, or at risk of, an indication associated with a TGF-beta deficiency comprising administering one or more agents that is effective to elevate the level of TGF-beta. The invention also provides novel compounds that elevate TGF-beta levels, as well as pharmaceutical compositions comprising compounds that elevate TGF-beta levels, and methods for detecting diseases associated with endothelial cell activation.

  本发明提供了一种治疗哺乳动物的方法，该哺乳动物具有或有可能具有与 TGF-beta 缺乏有关的适应症，该方法包括施用一种或多种能有效提高 TGF-beta 水平的制剂。本发明还提供了能提高TGF-beta水平的新型化合物、包含能提高TGF-beta水平的化合物的药物组合物，以及检测与内皮细胞活化相关的疾病的方法。
• Prevention and treatment of cardiovascular pathologies
  申请人：Grainger J. David

  公开号：US20060029986A1

  公开（公告）日：2006-02-09

  A method for treating or preventing cardiovascular pathologies by administering a compound of the formula (I): wherein Z is C═O or a covalent bond; Y is H or O(C 1 -C 4 )alkyl, R 1 and R 2 are individually (C 1 -C 4 )alkyl or together with N are a saturated heterocyclic group, R 3 is ethyl or chloroethyl, R 4 is H or together with R 3 is —CH 2 —CH 2 — or —S—, R 5 is I, O(C 1 -C 4 )alkyl or H and R 6 is 1, O(C 1 -C 4 )alkyl or H with the proviso that when R 4 , R 5 , and R 6 are H, R 3 is not ethyl; or a pharmaceutically acceptable salt thereof, effective to activate or stimulate production of TGF-beta to treat and/or prevent conditions such as atherosclerosis, thrombosis, myocardial infarction, and stroke is provided. Useful compounds include idoxifene and salts thereof. Further provided is a method for identifying a compound that is a TGF-beta activator or production stimulator is provided. Another embodiment of the invention is an assay or kit to determine TGF-beta in vitro. Also provided is a therapeutic method comprising inhibiting smooth muscle cell proliferation associated with procedural vascular trauma employing the administration of tamoxifen or structural analogs thereof, including compounds of formula (I).

  一种通过施用式(I)化合物治疗或预防心血管疾病的方法： 其中 Z 是 C═O 或共价键；Y 是 H 或 O（C 1 -C 4 )烷基，R 1 和 R 2 分别是（C 1 -C 4 )烷基或与 N 一起为饱和杂环基团，R 3 是乙基或氯乙基，R 4 是 H 或与 R 3 是-CH 2 -CH 2 - 或-S-，R 5 是 I、O(C 1 -C 4 烷基或 H，而 R 6 是 1、O(C 1 -C 4 烷基或 H，但当 R 4 , R 5 和 R 6 为 H，R 3 不是乙基；或其药学上可接受的盐，可有效激活或刺激 TGF-beta 的产生，从而治疗和/或预防动脉粥样硬化、血栓形成、心肌梗塞和中风等疾病。有用的化合物包括艾多昔芬及其盐类。本发明还提供了一种用于鉴定 TGF-beta 激活剂或生成刺激剂的化合物的方法。本发明的另一个实施方案是一种测定体外 TGF-beta 的检测方法或试剂盒。本发明还提供了一种治疗方法，包括通过施用他莫昔芬或其结构类似物（包括式 (I) 化合物）来抑制与程序性血管创伤相关的平滑肌细胞增殖。
• PREVENTION AND TREATMENT OF CARDIOVASCULAR PATHOLOGIES WITH TAMOXIFEN ANALOGUES
  申请人：NEORX CORPORATION

  公开号：EP0833624A2

  公开（公告）日：1998-04-08