tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate | 1004794-09-5

• 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: tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate
• 英文别名: Tert-butyl 4-[[6-chloro-4-(trifluoromethyl)pyridin-2-yl]methoxymethyl]-4-(4-fluorophenyl)piperidine-1-carboxylate
• CAS: 1004794-09-5
• 化学式: C₂₄H₂₇ClF₄N₂O₃
• 分子量: 502.937
• InChiKey: MBIZMHKZJHSSOI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  51.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate 在 sodium cyanoborohydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 2-氯-6-(((4-(4-氟苯基)-1-甲基哌啶-4-基)甲氧基)甲基)-4-(三氟甲基)吡啶
  参考文献：
  名称：

  Design, optimization, and in vivo evaluation of a series of pyridine derivatives with dual NK1 antagonism and SERT inhibition for the treatment of depression

  摘要：

  A series of substituted pyridines, ether linked to a phenylpiperidine core were optimized for dual NK1/SERT affinity. Optimization based on NK1/SERT binding affinities, and minimization of off-target ion channel activity lead to the discovery of compound 44. In vivo evaluation of 44 in the gerbil forced swim test (a depression model), and ex-vivo NK1/SERT receptor occupancy data support the potential of a dual acting compound for the treatment of depression. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.094
• 作为产物：
  描述：

  2-氯-6-甲基-4-(三氟甲基)吡啶 在 N-溴代丁二酰亚胺(NBS) 、 potassium tert-butylate 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 生成 tert-butyl 4-(((6-chloro-4-(trifluoromethyl)pyridine-2-yl)methoxy)methyl)-4-(4-fluorophenyl)piperidine-1-carboxylate
  参考文献：
  名称：

  Design, optimization, and in vivo evaluation of a series of pyridine derivatives with dual NK1 antagonism and SERT inhibition for the treatment of depression

  摘要：

  A series of substituted pyridines, ether linked to a phenylpiperidine core were optimized for dual NK1/SERT affinity. Optimization based on NK1/SERT binding affinities, and minimization of off-target ion channel activity lead to the discovery of compound 44. In vivo evaluation of 44 in the gerbil forced swim test (a depression model), and ex-vivo NK1/SERT receptor occupancy data support the potential of a dual acting compound for the treatment of depression. (c) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.11.094

文献信息

• [EN] SUBSTITUTED HETEROCYCLIC ETHERS AND THEIR USE IN CNS DISORDERS<br/>[FR] ÉTHERS HÉTÉROCYCLIQUES SUBSTITUÉS ET LEUR UTILISATION DANS DES TROUBLES DU SYSTÈME NERVEUX CENTRAL
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2009096941A1

  公开（公告）日：2009-08-06

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  这项发明涵盖了公式I的化合物，包括药用盐、它们的药物组合物以及它们在治疗中枢神经系统疾病中的用途。
• SUBSTITUTED HETEROCYCLIC ETHERS AND THEIR USE IN CNS DISORDERS
  申请人：Parker Michael F.

  公开号：US20080027056A1

  公开（公告）日：2008-01-31

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  该发明涵盖了I式化合物，包括药学上可接受的盐、它们的制药组合物以及它们在治疗中枢神经系统疾病方面的用途。
• Substituted Heterocyclic Ethers and Their Use in CNS Disorders
  申请人：Parker Michael F.

  公开号：US20090030040A1

  公开（公告）日：2009-01-29

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  该发明涵盖了I式化合物，包括药学上可接受的盐，它们的制药组合物以及它们在治疗中枢神经系统疾病方面的应用。
• US8071778B2
  申请人：——

  公开号：US8071778B2

  公开（公告）日：2011-12-06
• Design, optimization, and in vivo evaluation of a series of pyridine derivatives with dual NK1 antagonism and SERT inhibition for the treatment of depression
  作者：Kevin W. Gillman、Michael F. Parker、Mark Silva、Andrew P. Degnan、George O. Tora、Nicholas J. Lodge、Yu-Wen Li、Snjezana Lelas、Matthew Taber、Rudolf G. Krause、Robert L. Bertekap、Amy E. Newton、Rick L. Pieschl、Kelly D. Lengyel、Kim A. Johnson、Sarah J. Taylor、Joanne J. Bronson、John E. Macor

  DOI：10.1016/j.bmcl.2012.11.094

  日期：2013.1

  A series of substituted pyridines, ether linked to a phenylpiperidine core were optimized for dual NK1/SERT affinity. Optimization based on NK1/SERT binding affinities, and minimization of off-target ion channel activity lead to the discovery of compound 44. In vivo evaluation of 44 in the gerbil forced swim test (a depression model), and ex-vivo NK1/SERT receptor occupancy data support the potential of a dual acting compound for the treatment of depression. (c) 2012 Elsevier Ltd. All rights reserved.