(E)-1-<4-(2-chloroethoxy)phenyl>-1-(4-iodophenyl)-2-phenyl-1-butene | 116057-73-9

• 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)-1-<4-(2-chloroethoxy)phenyl>-1-(4-iodophenyl)-2-phenyl-1-butene
• 英文别名: E-1-[4-(2-chloroethoxy)phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene；1-(2-chloroethoxy)-4-[(E)-1-(4-iodophenyl)-2-phenylbut-1-enyl]benzene
• CAS: 116057-73-9
• 化学式: C₂₄H₂₂ClIO
• 分子量: 488.796
• InChiKey: YLLHULKNZUHCSG-VHXPQNKSSA-N

物化性质

• 熔点：
  94-96 °C
• 沸点：
  526.9±50.0 °C(Predicted)
• 密度：
  1.398±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.3
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  乙炔锂乙二胺配合物 、 (E)-1-<4-(2-chloroethoxy)phenyl>-1-(4-iodophenyl)-2-phenyl-1-butene 在 四(三苯基膦)钯 、 zinc(II) chloride 作用下， 生成 (Z)-1-<4-(2-chloroethoxy)phenyl>-1-(4-ethynylphenyl)-2-phenyl-1-butene
  参考文献：
  名称：

  Rationally Designed Analogs of Tamoxifen with Improved Calmodulin Antagonism

  摘要：

  Computerized molecular modeling studies on the interactions of the antiestrogen tamoxifen (1) and its analogues bound to the calcium-binding protein calmodulin have guided the rational design of more potent antagonists. Compounds with either three or four methylene units in the basic side chain or slim lipophilic 4-substituents were expected to be more potent. All compounds were tested for antagonism of the calmodulin-dependent activity of cAMP phosphodiesterase and for binding affinity to the estrogen receptor from rat uteri. Some compounds were assayed for cytotoxicity against MCF-7 breast tumor cells in vitro. Introduction of lipophilic 4-substituents was accomplished by using palladium(0)-catalyzed coupling reactions with a 4-iodinated precursor. Both the 4-ethynyl (16 and 17) and 4-butyl (18 and 19) compounds were more potent calmodulin antagonists than tamoxifen. Extension of the basic aminoethoxy side chain of 4-iodotamoxifen (3) and idoxifene (2) ((E)-1-[4-[2-(N-pyrrolidino)ethoxy]phenyl]-1-(4-iodophenyl)-2-phenyl-1-butene) by one or two methylene units resulted in modest gains in calmodulin antagonism (10-13). All the compounds assayed retained estrogen receptor binding characteristics. The compound possessing the optimal combination of calmodulin antagonism and estrogen receptor binding was 12 ((E)-1-[4-[3-(N-pyrrolidino)propoxy]phen 1-(4-iodophenyl)-2-phenyl-1-butene) (IC50 = 1.1 mu M, RBA = 23). Correlation between calmodulin antagonism and cytotoxicity was demonstrated for selected compounds.'

  DOI：

  10.1021/jm00002a005
• 作为产物：
  描述：

  2-氯苯乙醚 在 盐酸 、 三氟乙酸酐 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 72.0h， 生成 (E)-1-<4-(2-chloroethoxy)phenyl>-1-(4-iodophenyl)-2-phenyl-1-butene
  参考文献：
  名称：

  McCague, Raymond; Potter, Gerard A.; Jarman, Michael, Organic Preparations and Procedures International, 1994, vol. 26, # 3, p. 343 - 346

  摘要：

  DOI：

文献信息

• Derivatives of tamoxifen. Dependence of antiestrogenicity on the 4-substituent
  作者：Raymond McCague、Guy Leclercq、Nicole Legros、Joyce Goodman、G. Michael Blackburn、Michael Jarman、Allan B. Foster

  DOI：10.1021/jm00132a006

  日期：1989.12

  Further derivatives (formyl, hydroxymethyl, oxirane, mercapto) were prepared from 4-bromotamoxifen via the 4-lithio derivative. Several of the derivatives (Br, I, SMe, SOMe, SO2Me, oxirane, CHO, CH2OH) displayed a higher affinity for estrogen receptors (ER) of calf uterine cytosol than did tamoxifen, but there was no relationship between affinity to ER and the ability to inhibit the growth of the MCF-7

  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。
• Development of an Efficient and Stereoselective Manufacturing Route to Idoxifene
  作者：Karl W. Ace、Mark A. Armitage、Richard K. Bellingham、Paul D. Blackler、David S. Ennis、Nigel Hussain、David C. Lathbury、David O. Morgan、Noah O'Connor、Graham H. Oakes、Stephen C. Passey、Laurence C. Powling

  DOI：10.1021/op0100394

  日期：2001.9.1

  A literature route to 1-(2-4-[(E)-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine (idoxifene) has been modified to tackle various scale-up issues and provide initial supplies. A new highly efficient, robust, and stereoselective manufacturing route is described in detail. This route involves diastereoselective synthesis of tertiary alcohol (1RS,2SR)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-

  对 1-(2-4-[(E)-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine (idoxifene) 的文献途径进行了修改，以应对各种规模-up 问题并提供初始供应。详细描述了一种新的高效、稳健和立体选择性的制造路线。该路线涉及通过非对映选择性合成叔醇 (1RS,2SR)-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]butan-1-ol对酮 1-(4-碘苯基)-2-苯基-1-丁酮进行格氏加成，然后进行衍生化和立体选择性顺式消除，从而以优异的收率和几何纯度提供碘昔芬。还描述了使用 McMurry 低价钛偶联反应对碘多昔芬的更直接途径的评估。
• Iodotamoxifen derivatives and use for estrogen receptor-positive breast
  申请人：National Research Development Corporation

  公开号：US04839155A1

  公开（公告）日：1989-06-13

  Iodotamoxifen derivatives which are compounds of formula (3) ##STR1## wherein X represents 3- or 4- iodo and R.sup.1 and R.sup.2, which may be the same or different, represent C.sub.1-3 alkyl, especially methyl or ethyl, groups or R.sup.1 represents a hydrogen atom and R.sup.2 a C.sub.1-3 alkyl group or R.sup.1 and R.sup.2 together with the nitrogen atom to which they are attached represent a saturated heterocyclic group, especially a pyrrolidino, piperidino, 4-methylpiperidino or morpholino group, and their pharmaceutically acceptable acid addition salts are potent anti-estrogenic compounds useful for treatment of estrogen receptor-positive (hormone-dependent) breast cancers. Radioisotopic iodotamoxifen derivatives of formula (3) are useful in radiotherapy or gamma ray imaging of these cancers.

  Iodotamoxifen衍生物是公式（3）的化合物，其中X代表3或4-碘，R1和R2可以相同或不同，代表C1-3烷基，特别是甲基或乙基基团，或R1代表氢原子，R2代表C1-3烷基或R1和R2与它们连接的氮原子一起代表饱和的杂环基团，特别是吡咯烷基，哌嗪基，4-甲基哌嗪基或吗啡基，并且它们的药物可接受酸盐是有效的抗雌激素化合物，用于治疗雌激素受体阳性（激素依赖性）乳腺癌。公式（3）的放射性碘代tamoxifen衍生物在这些癌症的放射治疗或伽马射线成像中有用。
• WO2006/80022
  申请人：——

  公开号：——

  公开（公告）日：——
• Tamoxifen derivatives
  申请人：NATIONAL RESEARCH DEVELOPMENT CORPORATION

  公开号：EP0260066B1

  公开（公告）日：1990-05-09