phenyl (4-chloropyridin-3-yl)carbamate | 1257857-58-1

• 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: phenyl (4-chloropyridin-3-yl)carbamate
• 英文别名: (4-chloro-pyridin-3-yl)carbamic acid phenyl ester；phenyl N-(4-chloropyridin-3-yl)carbamate
• CAS: 1257857-58-1
• 化学式: C₁₂H₉ClN₂O₂
• mdl: MFCD25578642
• 分子量: 248.669
• InChiKey: FBDKDXXMMSSUBM-UHFFFAOYSA-N

物化性质

• 沸点：
  353.5±42.0 °C(Predicted)
• 密度：
  1.384±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  51.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  phenyl (4-chloropyridin-3-yl)carbamate 在 盐酸 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 1.0h， 生成 piperazine-1-carboxylic acid (4-chloro-pyridin-3-yl)amide
  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
• 作为产物：
  描述：

  3-氨基-4-氯吡啶 生成 phenyl (4-chloropyridin-3-yl)carbamate
  参考文献：
  名称：

  ACS Medicinal Chemistry Letters 2015, 6, 1204-1208

  摘要：

  DOI：

文献信息

• [EN] HETEROARYL-SUBSTITUTED SPIROCYCLIC DIAMINE UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] MODULATEURS D'AMIDE D'ACIDE GRAS HYDROLASE DE TYPE DIAMINE URÉE SPIROCYCLIQUE SUBSTITUÉE PAR UN GROUPE HÉTÉROARYLE
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010141817A1

  公开（公告）日：2010-12-09

  Certain heteroaryl-substituted spirocyclic diamine 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, energy metabolism disorders, and movement disorders (e.g., multiple sclerosis).

  描述了某些杂环取代的螺环二胺脲化合物，这些化合物可用作FAAH抑制剂。这些化合物可用于制药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、紊乱和条件的方法，如焦虑、疼痛、炎症、睡眠紊乱、进食紊乱、能量代谢紊乱和运动紊乱（例如多发性硬化）。
• [EN] ARYL-SUBSTITUTED HETEROCYCLIC UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] MODULATEURS HETEROCYCLIQUES A BASE D'UREE A SUBSTITUTION ARYLE DE L'HYDROLASE DES AMIDES D'ACIDES GRAS (FAAH)
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2010141809A1

  公开（公告）日：2010-12-09

  Certain aryl-substituted heterocyclic 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, energy metabolism disorders, and movement disorders (e.g., multiple sclerosis).

  描述了某些含芳基取代的杂环脲化合物，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、能量代谢障碍和运动障碍(例如多发性硬化)。
• Heteroarylureas with fused bicyclic diamine cores as inhibitors of fatty acid amide hydrolase
  作者：John M. Keith、William Jones、Joan M. Pierce、Mark Seierstad、James A. Palmer、Michael Webb、Mark Karbarz、Brian P. Scott、Sandy J. Wilson、Lin Luo、Michelle Wennerholm、Leon Chang、Michele Rizzolio、Raymond Rynberg、Sandra Chaplan、J. Guy Breitenbucher

  DOI：10.1016/j.bmcl.2020.127463

  日期：2020.10

  A series of mechanism-based heteroaryl urea fatty acid amide hydrolase (FAAH) inhibitors with fused bicyclic diamine cores is described. In contrast to compounds built around a piperazine core, most of the fused bicyclic diamine bearing analogs prepared exhibited greater potency against rFAAH than the human enzyme. Several compounds equipotent against both species were identified and profiled in vivo

  描述了一系列基于机制的具有稠合双环二胺核的杂芳基脲脂肪酸酰胺水解酶（FAAH）抑制剂。与围绕哌嗪核心构建的化合物形成对比，大多数制备的带有稠合双环二胺的类似物对rFAAH的抑制作用均比人类酶高。在体内鉴定并鉴定了对两种物种均等的几种化合物。
• [EN] MODULATORS OF FATTY ACID AMIDE HYDROLASE<br/>[FR] MODULATEURS DE L'AMIDE HYDROLASE D'ACIDE GRAS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2011139951A1

  公开（公告）日：2011-11-10

  4-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperazine-1 -carboxylic acid (4-chloro-pyridin-3-yl)-amide is described, which is useful as a FAAH modulator. 4-(2,2-Difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperazine-1 -carboxylic acid (4-chloro-pyridin-3-yl)-amide 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, energy metabolism disorders, and movement disorders (e.g., multiple sclerosis). A method of synthesizing 4- (2,2-difluoro-benzo[1,3]dioxol-5-ylmethyl)-piperazine-1 -carboxylic acid (4- chloro-pyridin-3-yl)-amide is also disclosed.

  描述了4-(2,2-二氟苯并[1,3]二噁英-5-基甲基)-哌嗪-1-羧酸(4-氯吡啶-3-基)-酰胺，该化合物可用作FAAH调节剂。4-(2,2-二氟苯并[1,3]二噁英-5-基甲基)-哌嗪-1-羧酸(4-氯吡啶-3-基)-酰胺可用于制备药物组合物，并用于治疗由脂肪酰胺水解酶(FAAH)活性介导的疾病状态、紊乱和情况，如焦虑、疼痛、炎症、睡眠障碍、进食障碍、能量代谢紊乱和运动障碍(例如多发性硬化)。还公开了合成4-(2,2-二氟苯并[1,3]二噁英-5-基甲基)-哌嗪-1-羧酸(4-氯吡啶-3-基)-酰胺的方法。
• HETEROARYL-SUBSTITUTED SPIROCYCLIC DIAMINE UREA MODULATORS OF FATTY ACID AMIDE HYDROLASE
  申请人：Breitenbucher J. Guy

  公开号：US20120083476A1

  公开（公告）日：2012-04-05

  Certain heteroaryl-substituted spirocyclic diamine 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, energy metabolism disorders, and movement disorders (e.g., multiple sclerosis).

  本文描述了某些杂环取代的螺环二胺尿素化合物，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酸酰胺水解酶（FAAH）活性介导的疾病状态，失调和情况的方法，例如焦虑，疼痛，炎症，睡眠障碍，进食障碍，能量代谢障碍和运动障碍（例如多发性硬化）。