(E)-3-iodotamoxifen | 116057-76-2

• 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: (E)-3-iodotamoxifen
• 英文别名: trans-3-Iodotamoxifen；3-iodotamoxifen；2-[4-[(1E)-1-(3-Iodophenyl)-2-phenyl-1-buten-1-yl]phenoxy]-N,N-dimethylethanamine；2-[4-[(E)-1-(3-iodophenyl)-2-phenylbut-1-enyl]phenoxy]-N,N-dimethylethanamine
• CAS: 116057-76-2
• 化学式: C₂₆H₂₈INO
• 分子量: 497.419
• InChiKey: JXGKDMBVOAZRLI-OCEACIFDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1-[4-(2-氯乙氧基)苯基]-2-乙基-2-苯乙酮 在 盐酸 、 正丁基锂 作用下， 以 乙醇 为溶剂， 反应 64.17h， 生成 (E)-3-iodotamoxifen
  参考文献：
  名称：

  他莫昔芬的衍生物。抗雌激素性对4-取代基的依赖性。

  摘要：

  描述了在1-苯环的4-位上取代的他莫昔芬衍生物的范围。合成4-碘-，4-溴-和4-（甲硫基）他莫昔芬的关键步骤是1,2-二芳基丁酮与（4-卤代苯基）锂或[4-（甲硫基）苯基]镁的反应溴化物。使用4-（甲硫基）他莫昔芬的氧化前体制备甲基亚磺酰基和甲基磺酰基衍生物。由4-溴苯莫西芬经由4-硫代衍生物制备其他衍生物（甲酰基，羟甲基，环氧乙烷，巯基）。几种衍生物（Br，I，SMe，SOMe，SO2Me，环氧乙烷，CHO，CH2OH）对小牛子宫细胞溶质的雌激素受体（ER）的亲和力高于他莫昔芬，但对ER的亲和力与体外抑制MCF-7乳腺癌细胞系生长的能力。

  DOI：

  10.1021/jm00132a006

文献信息

• An expeditious synthesis of tamoxifen, a representative SERM (selective estrogen receptor modulator), via the three-component coupling reaction among aromatic aldehyde, cinnamyltrimethylsilane, and β-chlorophenetole
  作者：Isamu Shiina、Yoshiyuki Sano、Kenya Nakata、Masahiko Suzuki、Toshikazu Yokoyama、Akane Sasaki、Tomoko Orikasa、Tomomi Miyamoto、Masahiko Ikekita、Yukitoshi Nagahara、Yoshimune Hasome

  DOI：10.1016/j.bmc.2007.09.008

  日期：2007.12

  three-component coupling reaction among aromatic aldehydes, cinnamyltrimethylsilane, and aromatic nucleophiles using HfCl(4) as a Lewis acid catalyst to produce 3,4,4-triarylbutene, that is also a valuable intermediate of the tamoxifen derivatives. The former strategy requires a total of 10 steps from the aldol formation to the final conversion to tamoxifen, whereas the latter needs only three or four steps

  开发了抗癌药物他莫昔芬及其衍生物的两种新的合成途径。第一条路线涉及苄基苯基酮与乙醛的醛醇缩合反应，然后在Cl（2）Si（OTf）（2）存在下用苯甲醚进行Friedel-Crafts取代，生成1,1,2-三芳基-3-乙酰氧基丁烷，他莫昔芬衍生物的前体。第二种方法利用HfCl（4）作为路易斯酸催化剂，利用芳香族醛类，肉桂基三甲基硅烷和芳香族亲核体之间的新型三组分偶联反应生成3,4,4-三芳基丁烯，这也是他莫昔芬衍生物的重要中间体。前一种策略从形成醛醇到最终转化为他莫昔芬共需要10个步骤，后者仅需三到四个步骤即可生产他莫昔芬和屈洛昔芬，包括侧链部分的安装和碱诱导的双键迁移以形成四取代的烯烃结构。这种合成策略似乎不仅可以制备他莫昔芬衍生物，而且可以制备其他SERM（选择性雌激素受体调节剂），包括雌激素依赖性乳腺癌和骨质疏松症药物，是一种新的实用途径。
• 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。