methyl 6-({[(1R)-1-(4-fluorophenyl)ethyl]amino}methyl)pyridine-2-carboxylate | 1398583-88-4

• 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: methyl 6-({[(1R)-1-(4-fluorophenyl)ethyl]amino}methyl)pyridine-2-carboxylate
• 英文别名: methyl 6-[[[(1R)-1-(4-fluorophenyl)ethyl]amino]methyl]pyridine-2-carboxylate
• CAS: 1398583-88-4
• 化学式: C₁₆H₁₇FN₂O₂
• 分子量: 288.322
• InChiKey: WDORQMHDWIMOFC-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 6-({[(1R)-1-(4-fluorophenyl)ethyl]amino}methyl)pyridine-2-carboxylate 在 三乙胺 、 lithium hydroxide 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 6-({[(1R)-1-(4-fluorophenyl)ethyl](quinolin-3-ylcarbonyl)amino}methyl)pyridine-2-carboxylic acid
  参考文献：
  名称：

  Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain

  摘要：

  The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 degrees C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.

  DOI：

  10.1021/ml500479v
• 作为产物：
  描述：

  6-甲酰基-2-吡啶甲酸甲酯 、 (R)-1-(4-氟苯基)乙胺 在 三乙酰氧基硼氢化钠 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以94%的产率得到methyl 6-({[(1R)-1-(4-fluorophenyl)ethyl]amino}methyl)pyridine-2-carboxylate
  参考文献：
  名称：

  Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain

  摘要：

  The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 degrees C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.

  DOI：

  10.1021/ml500479v

文献信息

• [EN] ARYL SUBSTITUTED CARBOXAMIDE DERIVATIVES AS TRPM8 MODULATORS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE SUBSTITUÉS PAR ARYLE EN TANT QUE MODULATEURS DE TRPM8
  申请人：PFIZER LTD

  公开号：WO2012120398A1

  公开（公告）日：2012-09-13

  The invention provides a compound of the formula (I): wherein A, R1, R2 and R3 are as defined herein, or a pharmaceutically acceptable salt thereof. Such compounds are small molecule TRPM8 blockers and therefore useful in the propylaxis or treatment of a wide range of diseases, conditions or syndromes, including cold allodynia and Raynaulds syndrome.

  本发明提供了一种化合物，其化学式为（I）：其中A、R1、R2和R3如本文所定义，或其药学上可接受的盐。这些化合物是小分子TRPM8阻断剂，因此在预防或治疗包括寒冷痛觉异常和雷诺综合征在内的各种疾病、症状或综合征中有用。