(2-amino-5-chloropyridin-3-yl)(2'-ethoxyphenyl)methanol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (2-amino-5-chloropyridin-3-yl)(2'-ethoxyphenyl)methanol
• 英文别名: (2-Amino-5-chloropyridin-3-yl)-(2-ethoxyphenyl)methanol
• 化学式: C₁₄H₁₅ClN₂O₂
• 分子量: 278.738
• InChiKey: BTBFHPMYUBZOPO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  68.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2-amino-5-chloropyridin-3-yl)(2'-ethoxyphenyl)methanol 在 三氟乙酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 48.0h， 生成 7-chloro-5-(2'-ethoxyphenyl)-3,5-dihydropyrido[2,3-e][1,4]thiazepin-2(1H)-one
  参考文献：
  名称：

  Neuroprotective profile of pyridothiazepines with blocking activity of the mitochondrial Na+/Ca2+ exchanger

  摘要：

  The mitochondrial Na+/Ca2+ exchanger plays an important role in the control of cytosolic Ca2+ cycling in excitable cells, essential for the regulation of a plethora of Ca2+-dependent physio-pathological events, such as apoptosis in the presence of a Ca2+ overload. There are very few pharmacological tools available to study both physiological and pathological implications of the mitochondrial Na+/Ca2+ exchanger, where the benzothiazepine CGP37157 is the best-known ligand, used since the 1980s. However, it is not an efficient blocker and lacks of selectivity, as also blocks several other cellular Ca2+ transporters. Moreover, CGP37157 is a very lipophilic drug, showing very poor water solubility, what has hindered its therapeutic use. Attempting to improve its pharmacokinetic profile as well as its potency and selectivity, we herein describe the synthesis of new CGP37157 analogs, where the benzene-fused ring has been replaced by a pyridine. On top of a better water solubility and lower log P value, some of these new pyridothiazepine derivatives also presented a higher capacity to regulate the mitochondrial Ca2+ clearance, while keeping the neuroprotective properties presented in the head compound CGP37157. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.043
• 作为产物：
  描述：

  2-乙氧基苯甲醛 在 叔丁基锂 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 28.25h， 生成 (2-amino-5-chloropyridin-3-yl)(2'-ethoxyphenyl)methanol
  参考文献：
  名称：

  Neuroprotective profile of pyridothiazepines with blocking activity of the mitochondrial Na+/Ca2+ exchanger

  摘要：

  The mitochondrial Na+/Ca2+ exchanger plays an important role in the control of cytosolic Ca2+ cycling in excitable cells, essential for the regulation of a plethora of Ca2+-dependent physio-pathological events, such as apoptosis in the presence of a Ca2+ overload. There are very few pharmacological tools available to study both physiological and pathological implications of the mitochondrial Na+/Ca2+ exchanger, where the benzothiazepine CGP37157 is the best-known ligand, used since the 1980s. However, it is not an efficient blocker and lacks of selectivity, as also blocks several other cellular Ca2+ transporters. Moreover, CGP37157 is a very lipophilic drug, showing very poor water solubility, what has hindered its therapeutic use. Attempting to improve its pharmacokinetic profile as well as its potency and selectivity, we herein describe the synthesis of new CGP37157 analogs, where the benzene-fused ring has been replaced by a pyridine. On top of a better water solubility and lower log P value, some of these new pyridothiazepine derivatives also presented a higher capacity to regulate the mitochondrial Ca2+ clearance, while keeping the neuroprotective properties presented in the head compound CGP37157. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.12.043

文献信息

• Neuroprotective profile of pyridothiazepines with blocking activity of the mitochondrial Na+/Ca2+ exchanger
  作者：Francisco J. Martínez-Sanz、Rocío Lajarín-Cuesta、Laura González-Lafuente、Ana J. Moreno-Ortega、Eva Punzón、María F. Cano-Abad、Cristóbal de los Ríos

  DOI：10.1016/j.ejmech.2015.12.043

  日期：2016.2

  The mitochondrial Na+/Ca2+ exchanger plays an important role in the control of cytosolic Ca2+ cycling in excitable cells, essential for the regulation of a plethora of Ca2+-dependent physio-pathological events, such as apoptosis in the presence of a Ca2+ overload. There are very few pharmacological tools available to study both physiological and pathological implications of the mitochondrial Na+/Ca2+ exchanger, where the benzothiazepine CGP37157 is the best-known ligand, used since the 1980s. However, it is not an efficient blocker and lacks of selectivity, as also blocks several other cellular Ca2+ transporters. Moreover, CGP37157 is a very lipophilic drug, showing very poor water solubility, what has hindered its therapeutic use. Attempting to improve its pharmacokinetic profile as well as its potency and selectivity, we herein describe the synthesis of new CGP37157 analogs, where the benzene-fused ring has been replaced by a pyridine. On top of a better water solubility and lower log P value, some of these new pyridothiazepine derivatives also presented a higher capacity to regulate the mitochondrial Ca2+ clearance, while keeping the neuroprotective properties presented in the head compound CGP37157. (C) 2015 Elsevier Masson SAS. All rights reserved.