3-[3-(4-fluorophenoxy)benzyl]-N-pyridin-3-ylpiperidine-1-carboxamide | 1229384-05-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 3-[3-(4-fluorophenoxy)benzyl]-N-pyridin-3-ylpiperidine-1-carboxamide
• 英文别名: 3-[[3-(4-fluorophenoxy)phenyl]methyl]-N-pyridin-3-ylpiperidine-1-carboxamide
• CAS: 1229384-05-7
• 化学式: C₂₄H₂₄FN₃O₂
• 分子量: 405.472
• InChiKey: ABYPVBAACIVXPR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-Boc-4-亚甲基哌啶 在 盐酸 、 三乙胺 、 9-硼双环[3.3.1]壬烷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 66.0h， 生成 3-[3-(4-fluorophenoxy)benzyl]-N-pyridin-3-ylpiperidine-1-carboxamide
  参考文献：
  名称：

  The SAR of brain penetration for a series of heteroaryl urea FAAH inhibitors

  摘要：

  The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4: 1 to as low as 0.02: 1 were obtained through relatively simple structural changes to various regions of the heteroaryl urea scaffold. It was not possible to predict the degree of central nervous system (CNS) penetration from the volumes of distribution (V-d) obtained from pharmacokinetic (PK) experiments as very high V(d)s did not correlate with high B/P ratios. Similarly, calculated topological polar surface areas (TPSAs) did not consistently correlate with the degree of brain penetration. The lowest B/P ratios were observed for those compounds that were significantly ionized at physiological pH. However, as this class of compounds inhibits the FAAH enzyme through covalent modification, low B/P ratios did not preclude effective central target engagement. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.05.001

文献信息

• [EN] HETEROARYL-SUBSTITUTED UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] MODULATEURS À BASE D'URÉE À SUBSTITUTION HÉTÉROARYLE D'AMIDE D'ACIDE GRAS HYDROLASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010068452A1

  公开（公告）日：2010-06-17

  Certain heteroaryl-substituted piperidinyl and piperazinyl urea compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, insulin resistance, diabetes, osteoporosis, and movement disorders (e.g., multiple sclerosis).

  描述了某些杂环取代的哌啶基和哌嗪基脲化合物，这些化合物可用作FAAH抑制剂。这些化合物可用于制备药物组合物，并用于治疗由脂肪酸酰胺水解酶（FAAH）活性介导的疾病状态、紊乱和症状，如焦虑、疼痛、炎症、睡眠障碍、进食障碍、胰岛素抵抗、糖尿病、骨质疏松症和运动障碍（例如多发性硬化）。
• HETEROARYL-SUBSTITUTED UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE
  申请人：Breitenbucher J. Guy

  公开号：US20110230490A1

  公开（公告）日：2011-09-22

  Certain heteroaryl-substituted piperidinyl and piperazinyl urea compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, insulin resistance, diabetes, osteoporosis, and movement disorders (e.g., multiple sclerosis).

  本文描述了某些杂环取代的哌啶基和哌嗪基脲类化合物，可用作FAAH抑制剂。这些化合物可用于制备药物组合物和治疗疾病、紊乱和由脂肪酰胺水解酶（FAAH）活性介导的病状，例如焦虑、疼痛、炎症、睡眠障碍、进食障碍、胰岛素抵抗、糖尿病、骨质疏松症和运动障碍（例如多发性硬化症）的方法。
• HETEROARYL SUBSTITUTED UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20140066412A1

  公开（公告）日：2014-03-06

  Certain heteroaryl-substituted piperidinyl and piperazinyl urea compounds are described, which are useful as FAAH inhibitors. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by fatty acid amide hydrolase (FAAH) activity, such as anxiety, pain, inflammation, sleep disorders, eating disorders, insulin resistance, diabetes, osteoporosis, and movement disorders (e.g., multiple sclerosis).

  本文描述了某些杂环取代的哌啶基和哌嗪基脲化合物，它们可用作FAAH抑制剂。这些化合物可用于药物组合物和治疗由脂肪酰胺水解酶（FAAH）活性介导的疾病状态、紊乱和病况的方法，例如焦虑、疼痛、炎症、睡眠障碍、进食障碍、胰岛素抵抗、糖尿病、骨质疏松症和运动障碍（例如多发性硬化症）。
• US8598356B2
  申请人：——

  公开号：US8598356B2

  公开（公告）日：2013-12-03
• The SAR of brain penetration for a series of heteroaryl urea FAAH inhibitors
  作者：John M. Keith、Mark S. Tichenor、Richard L. Apodaca、Wei Xiao、William M. Jones、Mark Seierstad、Joan M. Pierce、James A. Palmer、Michael Webb、Mark J. Karbarz、Brian P. Scott、Sandy J. Wilson、Michelle L. Wennerholm、Michele Rizzolio、Raymond Rynberg、Sandra R. Chaplan、J. Guy Breitenbucher

  DOI：10.1016/j.bmcl.2016.05.001

  日期：2016.7

  The SAR of brain penetration for a series of heteroaryl piperazinyl- and piperadinyl-urea fatty acid amide hydrolase (FAAH) inhibitors is described. Brain/plasma (B/P) ratios ranging from >4: 1 to as low as 0.02: 1 were obtained through relatively simple structural changes to various regions of the heteroaryl urea scaffold. It was not possible to predict the degree of central nervous system (CNS) penetration from the volumes of distribution (V-d) obtained from pharmacokinetic (PK) experiments as very high V(d)s did not correlate with high B/P ratios. Similarly, calculated topological polar surface areas (TPSAs) did not consistently correlate with the degree of brain penetration. The lowest B/P ratios were observed for those compounds that were significantly ionized at physiological pH. However, as this class of compounds inhibits the FAAH enzyme through covalent modification, low B/P ratios did not preclude effective central target engagement. (C) 2016 Elsevier Ltd. All rights reserved.