6-(4-{[3-(trifluoromethyl)benzyl]oxy}phenoxy)nicotinic acid | 639091-51-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(4-{[3-(trifluoromethyl)benzyl]oxy}phenoxy)nicotinic acid
• 英文别名: 6-[4-(3-Trifluoromethyl-benzyloxy)-phenoxy]-nicotinic acid；6-[4-[[3-(trifluoromethyl)phenyl]methoxy]phenoxy]pyridine-3-carboxylic acid
• CAS: 639091-51-3
• 化学式: C₂₀H₁₄F₃NO₄
• 分子量: 389.331
• InChiKey: HZQHMGXGXGECGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.17
• 重原子数：
  28.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  68.65
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  4-(aminomethyl)pyridin-2-amine dihydrochloride 、 6-(4-{[3-(trifluoromethyl)benzyl]oxy}phenoxy)nicotinic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以65%的产率得到N-[(2-aminopyridin-4-yl)methyl]-6-[4-[[3-(trifluoromethyl)phenyl]methoxy]phenoxy]pyridine-3-carboxamide
  参考文献：
  名称：

  Discovery of an N-(2-aminopyridin-4-ylmethyl)nicotinamide derivative: a potent and orally bioavailable NCX inhibitor

  摘要：

  Ca2+ overload in myocardial cells is responsible for arrhythmia. Sodium-calcium exchanger (NCX) inhibitors are more effective than sodium hydrogen exchanger (NHE) inhibitors with regard to modulation of Ca2+ overload, because NCX inhibitors can directly inhibit the influx of Ca2+ into cells. NCX is an attractive target for the treatment of heart failure and ischemia-reper-fusion. We have designed and synthesized a series of N-(2-aminopyridin-4-ylmethyl)nicotinamide derivatives, based on compound 5. We have discovered a novel NCX inhibitor (23h) with an IC50 value of 0.12 mu M against reverse NCX. The inhibitory activities of our NCX inhibitors against cytochrome P450 were also evaluated. The effects on heart failure and the pharmacokinetic profile of compound 23h are discussed. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.052
• 作为产物：
  描述：

  methyl 6-(4-hydroxyphenoxy)nicotinate 在 sodium hydroxide 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 5.0h， 生成 6-(4-{[3-(trifluoromethyl)benzyl]oxy}phenoxy)nicotinic acid
  参考文献：
  名称：

  Discovery of an N-(2-aminopyridin-4-ylmethyl)nicotinamide derivative: a potent and orally bioavailable NCX inhibitor

  摘要：

  Ca2+ overload in myocardial cells is responsible for arrhythmia. Sodium-calcium exchanger (NCX) inhibitors are more effective than sodium hydrogen exchanger (NHE) inhibitors with regard to modulation of Ca2+ overload, because NCX inhibitors can directly inhibit the influx of Ca2+ into cells. NCX is an attractive target for the treatment of heart failure and ischemia-reper-fusion. We have designed and synthesized a series of N-(2-aminopyridin-4-ylmethyl)nicotinamide derivatives, based on compound 5. We have discovered a novel NCX inhibitor (23h) with an IC50 value of 0.12 mu M against reverse NCX. The inhibitory activities of our NCX inhibitors against cytochrome P450 were also evaluated. The effects on heart failure and the pharmacokinetic profile of compound 23h are discussed. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.052