ethyl 5-bromo-6-methoxypicolinate | 1214337-82-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: ethyl 5-bromo-6-methoxypicolinate
• 英文别名: ethyl 5-bromo-6-methoxypyridine-2-carboxylate
• CAS: 1214337-82-2
• 化学式: C₉H₁₀BrNO₃
• 分子量: 260.087
• InChiKey: KNVOTXUOFWTQNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2933399090

反应信息

• 作为反应物：
  描述：

  ethyl 5-bromo-6-methoxypicolinate 在 copper(I) oxide 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 ethyl 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)picolinate
  参考文献：
  名称：

  Design and synthesis of dihydrobenzofuran amides as orally bioavailable, centrally active γ-secretase modulators

  摘要：

  We report the discovery and optimization of a novel series of dihydrobenzofuran amides as gamma-secretase modulators (GSMs). Strategies for aligning in vitro potency with drug-like physicochemical properties and good microsomal stability while avoiding P-gp mediated efflux are discussed. Lead compounds such as 35 and 43 have moderate to good in vitro potency and excellent selectivity against Notch. Good oral bioavailability was achieved as well as robust brain A beta 42 lowering activity at 100 mg/kg po dose. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.059
• 作为产物：
  描述：

  3-溴-2-氯吡啶 在 盐酸 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 96.0h， 生成 ethyl 5-bromo-6-methoxypicolinate
  参考文献：
  名称：

  Design and synthesis of dihydrobenzofuran amides as orally bioavailable, centrally active γ-secretase modulators

  摘要：

  We report the discovery and optimization of a novel series of dihydrobenzofuran amides as gamma-secretase modulators (GSMs). Strategies for aligning in vitro potency with drug-like physicochemical properties and good microsomal stability while avoiding P-gp mediated efflux are discussed. Lead compounds such as 35 and 43 have moderate to good in vitro potency and excellent selectivity against Notch. Good oral bioavailability was achieved as well as robust brain A beta 42 lowering activity at 100 mg/kg po dose. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.059

文献信息

• Novel Bicyclic Pyridinones
  申请人：Pettersson Martin Youngjin

  公开号：US20120252758A1

  公开（公告）日：2012-10-04

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药用可接受的盐被披露，其中所述化合物具有如本文所定义的Formula I的结构。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
• [EN] NOVEL HETEROARYL IMIDAZOLES AND HETEROARYL TRIAZOLES AS GAMMA-SECRETASE MODULATORS<br/>[FR] NOUVEAUX HÉTÉROARYL-IMIDAZOLES ET HÉTÉROARYL-TRIAZOLES À TITRE DE MODULATEURS DE GAMMA-SÉCRÉTASE
  申请人：PFIZER

  公开号：WO2011048525A1

  公开（公告）日：2011-04-28

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I; (I) as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  所述化合物及其药学上可接受的盐被披露，其中所述化合物具有如下式的结构；（I）如规范中定义的那样。相应的药物组合物、治疗方法、合成方法和中间体也被披露。
• Novel Heteroaryl Imidazoles And Heteroaryl Triazoles As Gamma-Secretase Modulators
  申请人：am Ende Christopher William

  公开号：US20120202787A1

  公开（公告）日：2012-08-09

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I; as defined in the specification. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  本文披露了化合物及其药学上可接受的盐，其中化合物具有I式结构，如规范中定义。还披露了相应的制药组合物、治疗方法、合成方法和中间体。
• Bicyclic pyridinones
  申请人：Pfizer Inc.

  公开号：US09067934B2

  公开（公告）日：2015-06-30

  Compounds and pharmaceutically acceptable salts of the compounds are disclosed, wherein the compounds have the structure of Formula I as defined herein. Corresponding pharmaceutical compositions, methods of treatment, methods of synthesis, and intermediates are also disclosed.

  本文披露了化合物及其医药上可接受的盐，其中化合物的结构符合此处定义的公式I。同时还披露了相应的制药组合物、治疗方法、合成方法和中间体。
• Novel S1P1 receptor agonists – Part 5: From amino-to alkoxy-pyridines
  作者：Martin H. Bolli、Cyrille Lescop、Magdalena Birker、Ruben de Kanter、Patrick Hess、Christopher Kohl、Oliver Nayler、Markus Rey、Patrick Sieber、Jörg Velker、Thomas Weller、Beat Steiner

  DOI：10.1016/j.ejmech.2016.03.020

  日期：2016.6

  In a previous communication we reported on the discovery of aminopyridine 1 as a potent, selective and orally active S1P(1) receptor agonist. More detailed studies revealed that this compound is phototoxic in vitro. As a result of efforts aiming at eliminating this undesired property, a series of alkoxy substituted pyridine derivatives was discovered. The photo irritancy factor (PIF) of these alkoxy pyridines was significantly lower than the one of aminopyridine 1 and most compounds were not phototoxic. Focused SAR studies showed, that 2-, 3-, and 4-pyridine derivatives delivered highly potent S1P(1) receptor agonists. While the 2-pyridines were clearly more selective against S1PR(3), the corresponding 3- or 4 pyridine analogues showed significantly longer oral half-lives and as a consequence longer pharmacological duration of action after oral administration. One of the best compounds, cyclopentoxy-pyridine 45b lacked phototoxicity, showed EC50 values of 0.7 and 140 nM on S1PR(1) and S1PR(3), respectively, and maximally reduced the blood lymphocyte count for at least 24 h after oral administration of 10 mg/kg to Wistar rats. (C) 2016 Elsevier Masson SAS. All rights reserved.