4-(2-溴乙氧基)-4'-羟基二苯甲酮 | 79578-62-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-(2-溴乙氧基)-4'-羟基二苯甲酮
• 英文名称: (4-(2-bromoethoxy)phenyl)(4-hydroxyphenyl)methanone
• 英文别名: 4-(2-Bromoethoxy)-4'-hydroxybenzophenone；[4-(2-bromoethoxy)phenyl]-(4-hydroxyphenyl)methanone
• CAS: 79578-62-4
• 化学式: C₁₅H₁₃BrO₃
• 分子量: 321.17
• InChiKey: LEVHOJCNGNSULG-UHFFFAOYSA-N

物化性质

• 熔点：
  139–142°C

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-溴乙氧基)-4'-羟基二苯甲酮 在 四氯化钛 、 sodium iodide 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 32.0h， 生成 endoxifen
  参考文献：
  名称：

  NOVEL COMPOUNDS HAVING ESTROGEN RECEPTOR ALPHA DEGRADATION ACTIVITY AND USES THEREOF

  摘要：

  本公开涉及具有雌激素受体α降解活性的新化合物，包含这些化合物的药物组合物，以及它们在预防和治疗癌症及相关疾病和症状中的应用。

  公开号：

  US20200157078A1
• 作为产物：
  描述：

  2-对溴苯氧基四氢吡喃 在 盐酸 、 重铬酸吡啶 、 1,1-二溴乙烷 、 碘 、 magnesium 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 36.5h， 生成 4-(2-溴乙氧基)-4'-羟基二苯甲酮
  参考文献：
  名称：

  雌激素三芳基乙烯乙酸：结构变化对MCF-7细胞中雌激素受体亲和力，雌激素效能和功效的影响。

  摘要：

  以（E，Z）-2- {4- [1- [对羟基苯基）-2-苯基] -1-丁烯基}苯氧基乙酸（8）为例的三芳基乙烯羧酸是一类新型的雌激素受体（ER）配体组织选择性雌激素激动剂和拮抗剂的作用。我们报告8和类似物的合成，结合已知或预期可促进三芳基乙烯中的ER亲和力的结构特征。这些研究表明，对羟基苯基部分，烯键和8的醚氧对于高ER亲和力都是至关重要的。尽管在其2-苯基环12上带有对-（氧乙酸）部分的1,1-双酚类似物具有较低的ER亲和力，但在MCF-7细胞中其雌激素效价接近8。与8是拮抗作用力弱的部分激动剂不同，12是完全激动剂。在9中看到了MCF-7细胞的效价/功效的相似图谱，其是8的烯键饱和类似物。他莫昔芬抗雌激素完全拮抗了8、9和12的生长促进作用，表明这种作用是介导的。仅通过ER。因此，我们在MCF-7细胞中的研究证实了8的雌激素性，并能够鉴定出具有良好雌激素效力和完全雌激素功效的两种类似物

  DOI：

  10.1021/jm960517e

文献信息

• ER PROTEIN REGULATORS AND USE THEREOF
  申请人：ShanghaiTech University

  公开号：US20220016102A1

  公开（公告）日：2022-01-20

  The present disclosure relates to an ER protein regulator compound represented by formula (I) and use thereof. LIN in the compound represented by formula (I) is a linker; ULM is a small-molecule ligand of VHL or CRBN protease having a ubiquitylation function; and group X is CH 2 , O or NH, and group X is covalently linked to ULM by means of the linker LIN. The designed and synthesized compounds of the present disclosure have wide pharmacological activity, has the function of regulating ER protein and inhibiting the activity of tumors, and can be used for preventing and/or treating diseases and disorders associated with estrogen receptors, or related tumor treatment.

  本公开涉及一种由式(I)表示的ER蛋白质调节剂化合物及其使用。式(I)中的LIN是连接剂；ULM是VHL或CRBN蛋白酶的小分子配体，具有泛素化功能；X基团为CH2、O或NH，X基团通过连接剂LIN与ULM共价连接。本公开设计和合成的化合物具有广泛的药理活性，具有调节ER蛋白质和抑制肿瘤活性的功能，并可用于预防和/或治疗与雌激素受体相关的疾病和紊乱，或相关肿瘤治疗。
• [EN] PROCESS FOR PREPARING (Z)-ENDOXIFEN OF HIGH PURITY<br/>[FR] PROCÉDÉ DE PRÉPARATION DE (Z)-ENDOXIFÈNE DE HAUTE PURETÉ
  申请人：US HEALTH

  公开号：WO2017070651A1

  公开（公告）日：2017-04-27

  Disclosed is a process for preparing (Z)-endoxifen, comprising (i) recrystallizing an input crystalline solid comprising a mixture of (Z)-endoxifen (1) and (E)-endoxifen (2) from a first solvent to provide a first crystalline solid and a first mother liquor, wherein the first mother liquor has a ratio of (1) to (2) at least 1.3 times greater than the ratio in the input crystalline solid (1) and (2); (ii) recrystallizing a solid produced by concentrating the first mother liquor, or by removal of the first solvent from the first mother liquor, from a second solvent to give a second crystalline solid and a second mother liquor; (iii) optionally recrystallizing the second crystalline solid from the second solvent one to five additional times to give a third crystalline solid; wherein the third crystalline solid has a ratio of (Z)-endoxifen (1) to (E)-endoxifen (2) greater than 20:1.

  本发明涉及制备(Z)-恩多西芬的方法，包括(i) 从第一溶剂中重新结晶输入晶体固体，该输入晶体固体包括(Z)-恩多西芬(1)和(E)-恩多西芬(2)的混合物，以提供第一晶体固体和第一母液，其中第一母液中(1)和(2)的比例至少比输入晶体固体中的比例高1.3倍；(ii) 从第二溶剂中重新结晶通过浓缩第一母液产生的固体，或通过从第一母液中去除第一溶剂而产生的固体，以给出第二晶体固体和第二母液；(iii) 可选地将第二晶体固体从第二溶剂中重新结晶一到五次，以得到第三晶体固体；其中第三晶体固体中(Z)-恩多西芬(1)和(E)-恩多西芬(2)的比例大于20:1。
• [EN] 7-NITROINDOLINE DERIVATIVES AND THEIR USES<br/>[FR] DERIVES DE 7-NITROINDOLINE ET LEURS UTILISATIONS
  申请人：MEDICAL RES COUNCIL

  公开号：WO2004085394A1

  公开（公告）日：2004-10-07

  7-nitroindoline compounds are disclosed that comprise a triplet sensitising group such as substituted or unsubstituted benzophenone group and can be used to cage effector species. In particular, the inclusion of a triplet sensitising group linked to the 4 or 5 position of a 7-nitroindoline derivative provides compounds which can be photolysed to release the effector species with unexpectedly enhanced photolysis efficiency. The triplet sensitising group may be linked directly to the 7-nitroindoline or via a spacer group. In some examples, the triplet sensitising group and/or the spacer group can be selected to enhance other properties of the caged compound such as its solubility, spectroscopic properties or stability (e.g. stability of the linkage between the nitroindoline moiety and the triplet sensitiser). This can help to improve the performance of the caged compound, especially in aqueous environments containing dissolved oxygen.

  本文介绍了一种包含三重敏化基团的7-硝基吲哚化合物，例如取代或未取代的苯基酮基团，并可用于封闭效应物种。特别是，将三重敏化基团连接到7-硝基吲哚衍生物的4或5位上，可提供可光解化合物，其光解效率意外增强，从而释放效应物种。三重敏化基团可以直接连接到7-硝基吲哚或通过间隔基团连接。在某些示例中，可以选择三重敏化基团和/或间隔基团以增强封闭化合物的其他性质，例如其溶解性，光谱性质或稳定性（例如硝基吲哚基团和三重敏化剂之间的连接的稳定性）。这有助于提高封闭化合物的性能，特别是在含有溶解氧的水环境中。
• Triarylethylene carboxylic acids with estrogenic activity
  申请人：University of Georgia Research Foundation, Inc.

  公开号：US05189212A1

  公开（公告）日：1993-02-23

  Nonsteroidal estrogenic triarylethylene carboxylic acids of the formula ##STR1## wherein R is (CH.sub.2).sub.m O or (CH.sub.2).sub.n, where m is an integer from 1 to 4 and n is an integer from 0 to 4, X is hydrogen or hydroxyl, Y is methyl, ethyl, chlorine, or bromine, and wherein the RCOOH and X moieties are either meta or para to the phenyl ethylene linkage. Examples of active compounds include 4-hydroxytamoxifen acid, 3-hydroxytamoxifen acid, 4-[1-(p-hydroxyphenyl)-2-phenyl-1-butenyl]benzoic acid and 4-[1-(p-hydroxyphenyl)-2-phenyl-1-butenyl]phenylacetic acid. Compositions containing these triarylethylene carboxylic acids can be administered to patients to alleviate medical conditions associated with a deficiency of estrogen, including osteoporosis, premenstrual syndrome, vasomotor symptoms associated with menopause, atrophic vaginitis, Kraurosis vulvae, female hypogonadism, primary ovarian failure, excessive hair growth and pr The U.S. Government has certain rights in this invention by virtue of grants from the National Institutes of Health.

  非甾体雌激素三芳基乙烯羧酸的化学式为##STR1## 其中R为(CH.sub.2).sub.m O或(CH.sub.2).sub.n，其中m为1到4的整数，n为0到4的整数，X为氢或羟基，Y为甲基、乙基、氯或溴，且RCOOH和X基团均为与苯乙烯链连接的间位或对位。活性化合物的例子包括4-羟基他莫昔芬酸、3-羟基他莫昔芬酸、4-[1-(对羟基苯基)-2-苯基-1-丁烯基]苯甲酸和4-[1-(对羟基苯基)-2-苯基-1-丁烯基]苯乙酸。含有这些三芳基乙烯羧酸的组合物可用于治疗与雌激素缺乏相关的医疗状况，包括骨质疏松症、经前综合征、与绝经相关的血管运动症状、萎缩性阴道炎、白斑病、女性性腺功能减退症、原发性卵巢功能不全、过度毛发生长等。美国政府根据国家卫生研究院的拨款拥有本发明的某些权利。
• Process for preparing Z-endoxifen of high purity
  申请人：THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：US10464881B2

  公开（公告）日：2019-11-05

  Disclosed is a process for preparing (Z)-endoxifen, comprising (i) recrystallizing an input crystalline solid comprising a mixture of (Z)-endoxifen (1) and (E)-endoxifen (2) from a first solvent to provide a first crystalline solid and a first mother liquor, wherein the first mother liquor has a ratio of (1) to (2) at least 1.3 times greater than the ratio in the input crystalline solid (1) and (2); (ii) recrystallizing a solid produced by concentrating the first mother liquor, or by removal of the first solvent from the first mother liquor, from a second solvent to give a second crystalline solid and a second mother liquor; (iii) optionally recrystallizing the second crystalline solid from the second solvent one to five additional times to give a third crystalline solid; wherein the third crystalline solid has a ratio of (Z)-endoxifen (1) to (E)-endoxifen (2) greater than 20:1.

  本发明公开了一种制备(Z)-恩多昔芬的工艺，包括(i)从第一溶剂中重结晶由(Z)-恩多昔芬(1)和(E)-恩多昔芬(2)混合物组成的输入结晶固体，以提供第一结晶固体和第一母液，其中第一母液的(1)与(2)之比至少是输入结晶固体(1)和(2)之比1.3 倍；(ii) 从第二溶剂中重结晶通过浓缩第一母液或通过从第一母液中去除第一溶剂而产生的固体，以得到第二结晶固体和第二母液；(iii) 可选地将第二结晶固体从第二溶剂中再结晶一至五次，得到第三结晶固 体；其中第三结晶固体的(Z)-恩多昔芬(1)与(E)-恩多昔芬(2)之比大于 20：1.