methyl 6-bromobenzo[b]thiophene-3-carboxylate | 946428-00-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: methyl 6-bromobenzo[b]thiophene-3-carboxylate
• 英文别名: methyl 6-bromo-1-benzothiophene-3-carboxylate
• CAS: 946428-00-8
• 化学式: C₁₀H₇BrO₂S
• 分子量: 271.134
• InChiKey: VPDDVKPIOCFHRM-UHFFFAOYSA-N

物化性质

• 沸点：
  358.9±22.0 °C(Predicted)
• 密度：
  1.622±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  54.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 6-bromobenzo[b]thiophene-3-carboxylate 、 在 tris-(dibenzylideneacetone)dipalladium(0) 、 caesium carbonate 、 potassium hydroxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 16.0h， 生成 6-(4-(((5-cyclopropyl-3-(2-(trifluoromethyl)phenyl)isoxazol-4-yl)methoxy)-methyl)-4-fluoropiperidin-1-yl)benzo[b]thiophene-3-carboxylic acid
  参考文献：
  名称：

  Discovery and Optimization of Non-bile Acid FXR Agonists as Preclinical Candidates for the Treatment of Nonalcoholic Steatohepatitis

  摘要：

  Farnesoid X receptor (FXR) plays a key role in bile acid homeostasis, inflammation, fibrosis, and metabolism of lipid and glucose and becomes a promising therapeutic target for nonalcoholic steatohepatitis (NASH) or other FXR-dependent diseases. The phase III trial results of obeticholic acid demonstrate that the FXR agonists emerge as a promising intervention in patients with NASH and fibrosis, but this bile acid-derived FXR agonist brings severe pruritus and an elevated risk of cardiovascular disease for patients. Herein, we reported our efforts in the discovery of a series of non-bile acid FXR agonists, and 36 compounds were designed and synthesized based on the structure-based drug design and structural optimization strategies. Particularly, compound 42 is a highly potent and selective FXR agonist, along with good pharmacokinetic profiles, high liver distribution, and preferable in vivo efficacy, indicating that it is a potential candidate for the treatment of NASH or other FXR-dependent diseases.

  DOI：

  10.1021/acs.jmedchem.0c01065
• 作为产物：
  描述：

  3-acetyl-6-bromobenzothiophene 在 sodium hydroxide 、 硫酸 、 溴 作用下， 反应 2.25h， 生成 methyl 6-bromobenzo[b]thiophene-3-carboxylate
  参考文献：
  名称：

  WO2007/140174

  摘要：

  公开号：

文献信息

• Bromination of 3-substituted benzo[b]thiophenes: access to Raloxifen intermediate
  作者：François Liger、Stéphane Pellet-Rostaing、Florence Popowycz、Marc Lemaire

  DOI：10.1016/j.tetlet.2011.05.043

  日期：2011.7

  A practical route to prepare halogeno-derivatives is described, starting from easily available 3-cyano-benzo[b]thiophene. Main efforts have been devoted to the optimization of the experimental procedures (solvent, bromination) to promote selectivity. Synthetic studies investigate the potential access to an advanced intermediate of Raloxifen.

  描述了从容易获得的3-氰基-苯并[ b ]噻吩开始制备卤代衍生物的实用途径。为了优化选择性，主要致力于优化实验程序（溶剂，溴化）。合成研究调查了使用Raloxifen的高级中间体的潜在途径。
• FXR AGONISTS
  申请人：Bell Michael Gregory

  公开号：US20090270460A1

  公开（公告）日：2009-10-29

  Compounds of formula wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.

  本发明公开了化学式为所定义变量的化合物及其制药组合物和使用方法，用于治疗血脂异常及相关疾病。
• Compounds and Methods for Modulating Fx-Receptors
  申请人：Bell Michael Gregory

  公开号：US20080306125A1

  公开（公告）日：2008-12-11

  Compounds of formula. wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.

  本发明涉及化合物的公式，其中变量如本文所定义，以及它们的药物组合物和使用方法，可用于治疗血脂异常和相关疾病。
• COMPOUNDS AND METHODS FOR MODULATING FXR
  申请人：Bell Michael Gregory

  公开号：US20090093524A1

  公开（公告）日：2009-04-09

  Compounds of formula (I) wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.

  公式（I）的化合物在此定义的变量下披露，它们的制药组合物和使用方法被用于治疗血脂异常和相关疾病。
• FXR agonists
  申请人：Eli Lilly and Company

  公开号：US07846960B2

  公开（公告）日：2010-12-07

  Compounds of formula wherein variables are as defined herein and their pharmaceutical compositions and methods of use are disclosed as useful for treating dyslipidemia and related diseases.

  公式中变量的化合物及其药物组合物和使用方法被披露为治疗血脂异常和相关疾病的有用药物。