2-[6-[[4-(4-Fluorophenyl)-1-methylpiperidin-4-yl]methoxymethyl]-4-(trifluoromethyl)pyridin-2-yl]-2-azabicyclo[3.1.0]hexane | 1416949-06-8

• 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: 2-[6-[[4-(4-Fluorophenyl)-1-methylpiperidin-4-yl]methoxymethyl]-4-(trifluoromethyl)pyridin-2-yl]-2-azabicyclo[3.1.0]hexane
• 英文别名: 2-[6-[[4-(4-fluorophenyl)-1-methylpiperidin-4-yl]methoxymethyl]-4-(trifluoromethyl)pyridin-2-yl]-2-azabicyclo[3.1.0]hexane
• CAS: 1416949-06-8
• 化学式: C₂₅H₂₉F₄N₃O
• 分子量: 463.518
• InChiKey: MZXMDLGAXKNSBN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  28.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 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 、 palladium diacetate 、 sodium cyanoborohydride 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三氟乙酸 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 生成 2-[6-[[4-(4-Fluorophenyl)-1-methylpiperidin-4-yl]methoxymethyl]-4-(trifluoromethyl)pyridin-2-yl]-2-azabicyclo[3.1.0]hexane
  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

• 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.