ethyl 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)picolinate | 1227082-74-7

• 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 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)picolinate
• 英文别名: 6-Methoxy-5-(4-methyl-1h-imidazol-1-yl)-2-pyridinecarboxylic acid ethyl ester；ethyl 6-methoxy-5-(4-methylimidazol-1-yl)pyridine-2-carboxylate
• CAS: 1227082-74-7
• 化学式: C₁₃H₁₅N₃O₃
• 分子量: 261.28
• InChiKey: VTEGTKLZIXCPBK-UHFFFAOYSA-N

物化性质

• 沸点：
  446.2±45.0 °C(Predicted)
• 密度：
  1.22±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  66.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 6-methoxy-5-(4-methyl-1H-imidazol-1-yl)picolinate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 以100%的产率得到6-methoxy-5-(4-methyl-1H-imidazol-1-yl).pyridine-2-carboxylic acid
  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：

  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

文献信息

• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE GAMMA SÉCRÉTASE
  申请人：SCHERING CORP

  公开号：WO2010056722A1

  公开（公告）日：2010-05-20

  In its many embodiments, the present invention provides a novel class of heterocyclic compounds of the formula: as modulators of gamma secretase, methods of preparing such compounds, pharmaceutical compositions containing one or more such compounds, methods of preparing pharmaceutical formulations comprising one or more such compounds, and methods of treatment, prevention, inhibition, or amelioration of one or more diseases associated with the central nervous system using such compounds or pharmaceutical compositions.

  在其多种实施方式中，本发明提供了一类新颖的杂环化合物，其化学式为：作为γ-分泌酶调节剂，制备这类化合物的方法，含有一种或多种这类化合物的药物组合物，制备包含一种或多种这类化合物的药物配方的方法，以及使用这类化合物或药物组合物治疗、预防、抑制或改善与中枢神经系统相关的一种或多种疾病的方法。
• GAMMA SECRETASE MODULATORS
  申请人：Schering Corporation

  公开号：EP2365973A1

  公开（公告）日：2011-09-21
• US8809318B2
  申请人：——

  公开号：US8809318B2

  公开（公告）日：2014-08-19