methyl 6-bromo-4-(ethyloxy)-2-quinolinecarboxylate | 1276656-45-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: methyl 6-bromo-4-(ethyloxy)-2-quinolinecarboxylate
• 英文别名: Methyl 6-bromo-4-ethoxy-2-quinolinecarboxylate；methyl 6-bromo-4-ethoxyquinoline-2-carboxylate
• CAS: 1276656-45-1
• 化学式: C₁₃H₁₂BrNO₃
• 分子量: 310.147
• InChiKey: ANUOLSUYNCMOIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 6-bromo-4-(ethyloxy)-2-quinolinecarboxylate 在 potassium phosphate 、 palladium diacetate 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 19.17h， 生成 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-4-(ethyloxy)-2-quinolinecarboxylic acid
  参考文献：
  名称：

  Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene

  摘要：

  To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.089
• 作为产物：
  描述：

  6-溴-4-羟基喹啉-2-甲酸甲酯 、 碘乙烷 在 silver carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 66.25h， 以57%的产率得到methyl 6-bromo-4-(ethyloxy)-2-quinolinecarboxylate
  参考文献：
  名称：

  Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene

  摘要：

  To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.089

文献信息

• SPIROCYCLIC COMPOUNDS AS FARNESOID X RECEPTOR MODULATORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20190127362A1

  公开（公告）日：2019-05-02

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of famesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式（I）的化合物或其立体异构体、互变异构体或药学上可接受的盐或溶剂，其中所有变量均如本说明中所定义。这些化合物调节法尼索德X受体（FXR）的活性，例如作为激动剂。本发明还涉及包含这些化合物的药物组合物以及使用这些化合物和药物组合物治疗与FXR失调相关的疾病、紊乱或情况的方法，例如病理纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• Spirocyclic compounds as farnesoid X receptor modulators
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US11078198B2

  公开（公告）日：2021-08-03

  The present invention provides compounds of Formula (I): or stereoisomers, tautomers, or pharmaceutically acceptable salts or solvates thereof, wherein all the variables are as defined herein. These compounds modulate the activity of famesoid X receptor (FXR), for example, as agonists. This invention also relates to pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

  本发明提供了式 (I) 的化合物： 或其立体异构体、同系物或药学上可接受的盐或溶液，其中所有变量如本文所定义。这些化合物可调节类法莫司 X 受体（FXR）的活性，例如作为激动剂。本发明还涉及包含这些化合物的药物组合物，以及通过使用这些化合物和药物组合物治疗与 FXR 失调相关的疾病、紊乱或病症的方法，例如病理性纤维化、移植排斥、癌症、骨质疏松症和炎症性疾病。
• Conformationally constrained farnesoid X receptor (FXR) agonists: Heteroaryl replacements of the naphthalene
  作者：Jonathan Y. Bass、Justin A. Caravella、Lihong Chen、Katrina L. Creech、David N. Deaton、Kevin P. Madauss、Harry B. Marr、Robert B. McFadyen、Aaron B. Miller、Wendy Y. Mills、Frank Navas、Derek J. Parks、Terrence L. Smalley、Paul K. Spearing、Dan Todd、Shawn P. Williams、G. Bruce Wisely

  DOI：10.1016/j.bmcl.2010.12.089

  日期：2011.2

  To improve on the drug properties of GSK8062 1b, a series of heteroaryl bicyclic naphthalene replacements were prepared. The quinoline 1c was an equipotent FXR agonist with improved drug developability parameters relative to 1b. In addition, analog 1c lowered body weight gain and serum glucose in a DIO mouse model of diabetes. (C) 2010 Elsevier Ltd. All rights reserved.