1-(4-羟基苄基)-2-(4-羟基苯基)-3-甲基-1H-吲哚-5-醇 | 104599-10-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 1-(4-羟基苄基)-2-(4-羟基苯基)-3-甲基-1H-吲哚-5-醇
• 中文别名: 醋酸巴多西芬杂质3；巴多昔芬杂质9；巴多昔芬杂质
• 英文名称: des(1-azepanyl)ethyl bazedoxifene
• 英文别名: 1-(4-Hydroxybenzyl)-2-(4-hydroxyphenyl)-3-methyl-1h-indol-5-ol；2-(4-hydroxyphenyl)-1-[(4-hydroxyphenyl)methyl]-3-methylindol-5-ol
• CAS: 104599-10-2
• 化学式: C₂₂H₁₉NO₃
• 分子量: 345.398
• InChiKey: JPMOCTUKPAGCTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  65.6
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 1-(4-羟基苄基)-2-(4-羟基苯基)-3-甲基-1H-吲哚-5-醇 在 吡啶 作用下， 反应 2.0h， 生成 [4-[[5-acetyloxy-2-(4-acetyloxyphenyl)-3-methylindol-1-yl]methyl]phenyl] acetate
  参考文献：
  名称：

  2-Phenylindoles. Effect of N-benzylation on estrogen receptor affinity, estrogenic properties, and mammary tumor inhibiting activity

  摘要：

  Hydroxy-2-phenylindoles carrying substituted benzyl groups and similar substituents at the nitrogen were synthesized and tested for their ability to displace estradiol from its receptor. All of the derivatives tested exhibited high binding affinities for the calf uterine estrogen receptor, with RBA values ranging from 0.55 to 16 (estradiol 100). The mouse uterine weight tested revealed only low estrogenicity for this class of compounds. Several derivatives showed antiestrogenic activity with a maximum inhibition of estrone-stimulated uterine growth of 40%. Two of the compounds (6c, 21c) were tested for antitumor activity in dimethylbenanthracene- (DMBA-) induced estrogen-dependent rat mammary tumors. Only the 4-cyanobenzyl derivative 21c was active. After 4 weeks of treatment with 12 mg/kg (6 times/week), the average tumor area was decreased by 57% (control +204%). In vitro, an inhibitory effect of 21b was only observed with hormone-sensitive MCF-7 breast cancer cells but not with hormone-independent MDA-MB 231 cells. These results make a mode of action involving the estrogen receptor system likely.

  DOI：

  10.1021/jm00384a022
• 作为产物：
  描述：

  3-甲基-5-苄氧基-2-(4-苄氧基苯基)-1H-吲哚 在 20% palladium hydroxide-activated charcoal 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 3.67h， 生成 1-(4-羟基苄基)-2-(4-羟基苯基)-3-甲基-1H-吲哚-5-醇
  参考文献：
  名称：

  2-苯基吲哚的合成，抗增殖和促凋亡活性。

  摘要：

  乳腺癌是仅次于肺癌的全球第二大常见癌症，绝大多数早期乳腺癌是激素依赖性的。乳腺癌临床治疗中的主要治疗进展之一是选择性雌激素受体调节剂（SERM）的引入。我们描述了基于2-芳基吲哚支架的新型SERM型配体的设计和合成，以选择性靶向激素依赖性乳腺癌中的雌激素受体。这些新颖的化合物中有一些被设计为双吲哚型结构，而另一些则与基于康维他汀A4（CA4）的细胞毒剂结合，后者是微管蛋白聚合的有效抑制剂。在该项目中合成的吲哚化合物（例如31和86）在ER阳性MCF-7乳腺癌细胞系中表现出雌激素受体（ER）结合和强大的抗增殖活性，IC50值分别为2.71μM和1.86μM。这些活性化合物在MCF-7细胞中诱导凋亡活性，而对正常外周血细胞的影响最小。它们的强抗癌作用可能是由两个31的ER结合配体和一个与86的细胞毒性剂结合的ER结合配体介导的。

  DOI：

  10.1016/j.bmc.2016.06.050

文献信息

• SALTS OF BAZEDOXIFENE
  申请人：Jirman Josef

  公开号：US20100240888A1

  公开（公告）日：2010-09-23

  The invention deals with new crystalline salts of bazedoxifene, by means of which a high API quality can be achieved in a high yield.

  这项发明涉及巴泽度西酚的新结晶盐，通过这种方式可以在高产率下实现高API质量。
• PROCESSES FOR THE SYNTHESIS OF BAZEDOXIFENE ACETATE AND INTERMEDIATES THEREOF
  申请人：Joshi Shreerang

  公开号：US20120253038A1

  公开（公告）日：2012-10-04

  Efficient processes for the synthesis of pharmaceutically useful compounds such as (1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol acetic acid commonly known as bazedoxifene acetate (Formula IX) using cyanomethoxybenzyl halides of Formula III, where X=Halogens e.g., Cl, F, Br, I; G=Any electron donating or electron withdrawing substituent.

  高效合成药用化合物的过程，如(1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1H-indol-5-ol 醋酸，通常称为bazedoxifene 醋酸盐（化学式 IX），使用公式 III 中的氰甲氧基苄卤代物，其中 X=卤素，如 Cl、F、Br、I；G=任何电子给体或电子受体取代基。
• [EN] PROCESSES FOR THE SYNTHESIS OF BAZEDOXIFENE ACETATE AND INTERMEDIATES THEREOF<br/>[FR] PROCÉDÉS POUR LA SYNTHÈSE D'ACÉTATE DE BAZÉDOXIFÈNE ET INTERMÉDIAIRES CORRESPONDANTS
  申请人：SANDOZ AG

  公开号：WO2010118997A1

  公开（公告）日：2010-10-21

  Efficient processes for the synthesis of pharmaceutically useful compounds such as (1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1 H-indol-5-ol acetic acid commonly known as bazedoxifene acetate (Formula IX) using cyanomethoxybenzyl halides of Formula III, where X = Halogens e.g., Cl, F, Br, I; G = Any electron donating or electron withdrawing substituent.

  使用氰甲氧基苯甲基卤代物（公式III，其中X=卤素，如Cl，F，Br，I; G = 任何电子供体或电子吸引基团）进行合成，可以高效地合成对药物有用的化合物，例如（1-[4-(2-azepan-1-yl-ethoxy)-benzyl]-2-(4-hydroxy-phenyl)-3-methyl-1 H-indol-5-ol乙酸盐，通常称为bazedoxifene乙酸盐（公式IX）。
• New polymorphic form of bazedoxifene acetate
  申请人：Zentiva, K.S.

  公开号：EP2311805A1

  公开（公告）日：2011-04-20

  New acetate salt of bazedoxifene, which is preferably characterized by the following reflections in the X-Ray diffraction pattern: 13.17; 15.97; 17.95; 19.62; 20.54; 22.08; 25.27.

  巴达昔芬的新型醋酸盐，其 X 射线衍射图谱中的反射率如下：13.17；15.97；17.95；19.62；20.54；22.08；25.27。
• Tethered indoles as functionalizable ligands for the estrogen receptor
  作者：Bridget G. Trogden、Sung Hoon Kim、Shuyi Lee、John A. Katzenellenbogen

  DOI：10.1016/j.bmcl.2008.11.043

  日期：2009.1

  To create ligands for the estrogen receptor that contain pendant groups for tethering to a poly(amido)amine (PAMAM) dendrimer, we have explored a class of N-substituted 2-phenyl indoles. Attachment of tethers of different length and chemical nature to this non-steroidal indole scaffold gave high affinity ligand-tether conjugates that can be easily functionalized. To further explore the utility of this system, an indole-conjugated dendrimer was prepared and evaluated as an estrogen receptor ligand. (C) 2008 Elsevier Ltd. All rights reserved.