5-benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(2-bromo-ethoxy)-benzyl]-3-methyl-1H-indole | 198480-07-8

• 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
• 英文名称: 5-benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(2-bromo-ethoxy)-benzyl]-3-methyl-1H-indole
• 英文别名: 1-[[4-(2-Bromoethoxy)phenyl]methyl]-3-methyl-5-phenylmethoxy-2-(4-phenylmethoxyphenyl)indole
• CAS: 198480-07-8
• 化学式: C₃₈H₃₄BrNO₃
• 分子量: 632.597
• InChiKey: MOQFXTHUZBWNNP-UHFFFAOYSA-N

物化性质

• 沸点：
  769.5±60.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  43
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  32.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(2-bromo-ethoxy)-benzyl]-3-methyl-1H-indole 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 1-[[4-[2-(氮杂环庚烷-1-基)乙氧基]苯基]甲基]-2-(4-羟基苯基)-3-甲基-吲哚-5-醇
  参考文献：
  名称：

  Design, Synthesis, and Preclinical Characterization of Novel, Highly Selective Indole Estrogens

  摘要：

  DOI：

  10.1021/jm010086m
• 作为产物：
  描述：

  对羟基苯甲醇 在 lithium aluminium tetrahydride 、 氯化亚砜 、 四溴化碳 、 sodium hydride 、 potassium carbonate 、 N,N-二甲基甲酰胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 1.58h， 生成 5-benzyloxy-2-(4-benzyloxy-phenyl)-1-[4-(2-bromo-ethoxy)-benzyl]-3-methyl-1H-indole
  参考文献：
  名称：

  In vitro bioactivation of bazedoxifene and 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol in human liver microsomes

  摘要：

  Bazedoxifene is a selective estrogen receptor modulator (SERM) that has been developed for use in postmenopausal osteoporosis. However, it contains a potentially toxic 5-hydroxy-3-methylindole moiety. Previous studies on the 5-hydroxyindole and the 3-alkylindole-containing drugs indometacine, zafirlukast and MK-0524 structural analogs have shown that they are bioactivated by cytochrome P450s through a dehydrogenation process to form quinoneimine or 3-methyleneindolenine electrophilic species. In the present study, bazedoxifene was synthesized and then evaluated, together with raloxifene and 2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol (13), a 3-methyl-5-hydroxyindole-based structural fragment of bazedoxifene, for its ability to form reactive electrophilic species when incubated with human liver microsomes (HLMs) or recombinant CYP isozymes. We showed that bazedoxifene was bioactivated only in trace amounts with recombinant CYP isozymes. In contrast, the N-dealkylated fragment of bazedoxifene (2-(4-hydroxyphenyl)-3-methyl-1H-indol-5-ol) was bioactivated in considerable amounts to an electrophilic intermediate, which was trapped with glutathione and identified by LC-MS/MS. This suggests that bazedoxifene would require initial N-dealkylation, which could subsequently lead to the formation of the reactive intermediate. However, such an N-dealkylated metabolite of bazedoxifene was not detected after the incubation of bazedoxifene in HLM or recombinant CYP isozymes. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.cbi.2012.03.001

文献信息

• 2-phenyl-1-[4-(2-aminoethoxy)-benzyl]-indoles as estrogenic agents
  申请人：American Home Products Corporation

  公开号：US05998402A1

  公开（公告）日：1999-12-07

  The present invention relates to new 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds which are useful as estrogenic agents, as well as pharmaceutical compositions and methods of treatment utilizing these compounds, which have the general structures below: ##STR1##

  本发明涉及新的2-苯基-1-[4-(2-氨基乙氧基)苄基]-吲哚化合物，其可用作雌激素类药物，以及利用这些化合物的药物组合物和治疗方法，其具有以下一般结构：##STR1##
• [EN] PREPARATION OF BAZEDOXIFENE AND ITS SALTS<br/>[FR] PRÉPARATION DE BAZÉDOXIFÈNE ET DE SES SELS
  申请人：REDDYS LAB LTD DR

  公开号：WO2011022596A2

  公开（公告）日：2011-02-24

  Processes for preparing bazedoxifene and its pharmaceutically acceptable salts, substantially free from process related impurities and process intermediates.

  制备巴泽度芬及其药用可接受盐的过程，基本上不含有与过程相关的杂质和过程中间体。
• 2-PHENYL-1-[4-(2-AMINOETHOXY)-BENZYL]-INDOLES AS ESTROGENIC AGENTS
  申请人：Miller P. Chris

  公开号：US20060094711A1

  公开（公告）日：2006-05-04

  The present invention relates to new 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds having the general structures below: which are useful in treating uterine leiomyoma.

  本发明涉及具有下列一般结构的新型2-苯基-1-[4-(2-氨基乙氧基)苄基]-吲哚化合物，其可用于治疗子宫平滑肌瘤。
• 2-phenyl-1- [4- (2-aminoethoxy) - benzyl] - indoles as estrogenic agents
  申请人：——

  公开号：US20010021719A1

  公开（公告）日：2001-09-13

  The present invention relates to new 2-Phenyl-1-[(2-Aminoethoxy)-Benzyl]-Indole compounds which are usefuil as estrogenic agents, as well as pharmaceutical compositions and methods of treatment utiig these compounds, which have the general structures below: 1

  本发明涉及新的2-苯基-1-[(2-氨乙氧基)苄基]-吲哚化合物，其作为雌激素类药物有用，以及使用这些化合物的药物组合物和治疗方法，其通用结构如下：1
• 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indoles as estrogenic agents
  申请人：Wyeth

  公开号：US20040229932A1

  公开（公告）日：2004-11-18

  The present invention relates to new 2-Phenyl-1-[4-(2-Aminoethoxy)-Benzyl]-Indole compounds which are useful as estrogenic agents, as well as pharmaceutical compositions and methods of treatment utilizing these compounds, which have the general structures below: 1

  本发明涉及新的2-苯基-1-[4-(2-氨基乙氧基)苄基]-吲哚化合物，其作为雌激素类药物有用，以及利用这些化合物的制药组合物和治疗方法，其具有以下一般结构：1。