4-[[3-(4-chlorophenoxy)phenyl]methyl]-N-(1,2-oxazol-3-yl)piperazine-1-carboxamide | 1093209-38-1

• 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: 4-[[3-(4-chlorophenoxy)phenyl]methyl]-N-(1,2-oxazol-3-yl)piperazine-1-carboxamide
• CAS: 1093209-38-1
• 化学式: C₂₁H₂₁ClN₄O₃
• 分子量: 412.876
• InChiKey: DSAYICXCSHNPSS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  70.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  tert-butyl 4-(3-(4-chlorophenoxy)benzyl)piperazine-1-carboxylate 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙腈 为溶剂， 反应 47.0h， 生成 4-[[3-(4-chlorophenoxy)phenyl]methyl]-N-(1,2-oxazol-3-yl)piperazine-1-carboxamide
  参考文献：
  名称：

  Heteroaryl urea inhibitors of fatty acid amide hydrolase: Structure–mutagenicity relationships for arylamine metabolites

  摘要：

  The structure-activity relationships for a series of heteroaryl urea inhibitors of fatty acid amide hydrolase (FAAH) are described. Members of this class of inhibitors have been shown to inactivate FAAH by covalent modification of an active site serine with subsequent release of an aromatic amine from the urea electrophile. Systematic Ames II testing guided the optimization of urea substituents by defining the structure-mutagenicity relationships for the released aromatic amine metabolites. Potent FAAH inhibitors were identified having heteroaryl amine leaving groups that were non-mutagenic in the Ames II assay. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.076

文献信息

• HETEROARYL-SUBSTITUTED UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE
  申请人：Apodaca Richard

  公开号：US20090062294A1

  公开（公告）日：2009-03-05

  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).

  本文描述了一些含有杂环芳基取代的哌啶基和哌嗪基脲类化合物，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和治疗由脂肪酸酰胺水解酶（FAAH）活性介导的疾病状态、障碍和症状的方法，例如焦虑、疼痛、炎症、睡眠障碍、进食障碍、胰岛素抵抗、糖尿病、骨质疏松和运动障碍（例如多发性硬化症）。
• Heteroaryl urea inhibitors of fatty acid amide hydrolase: Structure–mutagenicity relationships for arylamine metabolites
  作者：Mark S. Tichenor、John M. Keith、William M. Jones、Joan M. Pierce、Jeff Merit、Natalie Hawryluk、Mark Seierstad、James A. Palmer、Michael Webb、Mark J. Karbarz、Sandy J. Wilson、Michelle L. Wennerholm、Filip Woestenborghs、Dominiek Beerens、Lin Luo、Sean M. Brown、Marlies De Boeck、Sandra R. Chaplan、J. Guy Breitenbucher

  DOI：10.1016/j.bmcl.2012.10.076

  日期：2012.12

  The structure-activity relationships for a series of heteroaryl urea inhibitors of fatty acid amide hydrolase (FAAH) are described. Members of this class of inhibitors have been shown to inactivate FAAH by covalent modification of an active site serine with subsequent release of an aromatic amine from the urea electrophile. Systematic Ames II testing guided the optimization of urea substituents by defining the structure-mutagenicity relationships for the released aromatic amine metabolites. Potent FAAH inhibitors were identified having heteroaryl amine leaving groups that were non-mutagenic in the Ames II assay. (C) 2012 Elsevier Ltd. All rights reserved.
• [EN] HETEROARYL-SUBSTITUTED UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] MODULATEURS DE L'URÉE SUBSTITUÉS HÉTÉROARYLE DAMIDE 'HYDROLASE D'ACIDES GRAS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2008153752A2

  公开（公告）日：2008-12-18

  [EN] 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).
  [FR] L'invention concerne certains composés uréiques substitués hétéroaryle de pipéridinyle et pipérazinyle qui sont utiles en tant qu'inhibiteurs de la FAAH. De tels composés peuvent être utilisés dans des compositions pharmaceutiques et dans le cadre de méthodes de traitement de maladies, de troubles et de manifestations pathologiques induites par l'amide hydrolase d'acides gras, notamment l'anxiété, la douleur, l'inflammation, les troubles de sommeil, les troubles de l'alimentation, la résistance à l'insuline, le diabète, l'ostéoporose et les troubles moteurs (comme par exemple dans la sclérose en plaques).
• 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.