6-bromo-N-[4-[4-(2-methoxyphenyl)-1,4-diazepan-1-yl]butyl]nicotinamide | 1435685-96-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 6-bromo-N-[4-[4-(2-methoxyphenyl)-1,4-diazepan-1-yl]butyl]nicotinamide
• 英文别名: 6-bromo-N-[4-[4-(2-methoxyphenyl)-1,4-diazepan-1-yl]butyl]pyridine-3-carboxamide
• CAS: 1435685-96-3
• 化学式: C₂₂H₂₉BrN₄O₂
• 分子量: 461.402
• InChiKey: YEQXLZYCVNXKRF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  57.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  高哌嗪 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 potassium carbonate 、 1-羟基苯并三唑 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 一水合肼 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 86.0h， 生成 6-bromo-N-[4-[4-(2-methoxyphenyl)-1,4-diazepan-1-yl]butyl]nicotinamide
  参考文献：
  名称：

  Evaluation of N-phenyl homopiperazine analogs as potential dopamine D3 receptor selective ligands

  摘要：

  A series of N-(2-methoxyphenyl) homopiperazine analogs was prepared and their affinities for dopamine D-2, D-3, and D-4 receptors were measured using competitive radioligand binding assays. Several ligands exhibited high binding affinity and selectivity for the D-3 dopamine receptor compared to the D-2 receptor subtype. Compounds 11a, 11b, 11c, 11f, 11j and 11k had Ki values ranging from 0.7 to 3.9 nM for the D-3 receptor with 30- to 170-fold selectivity for the D-3 versus D-2 receptor. Calculated log P values (logP = 2.6-3.6) are within the desired range for passive transport across the blood-brain barrier. When the binding and the intrinsic efficacy of these phenylhomopiperazines was compared to those of previously published phenylpiperazine analogues, it was found that (a) affinity at D-2 and D-3 dopamine receptors generally decreased, (b) the D-3 receptor binding selectivity (D-2:D-3 K-i value ratio) decreased and, (c) the intrinsic efficacy, measured using a forskolin-dependent adenylyl cyclase inhibition assay, generally increased. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.074

文献信息

• Evaluation of N-phenyl homopiperazine analogs as potential dopamine D3 receptor selective ligands
  作者：Aixiao Li、Yogesh Mishra、Maninder Malik、Qi Wang、Shihong Li、Michelle Taylor、David E. Reichert、Robert R. Luedtke、Robert H. Mach

  DOI：10.1016/j.bmc.2013.03.074

  日期：2013.6

  A series of N-(2-methoxyphenyl) homopiperazine analogs was prepared and their affinities for dopamine D-2, D-3, and D-4 receptors were measured using competitive radioligand binding assays. Several ligands exhibited high binding affinity and selectivity for the D-3 dopamine receptor compared to the D-2 receptor subtype. Compounds 11a, 11b, 11c, 11f, 11j and 11k had Ki values ranging from 0.7 to 3.9 nM for the D-3 receptor with 30- to 170-fold selectivity for the D-3 versus D-2 receptor. Calculated log P values (logP = 2.6-3.6) are within the desired range for passive transport across the blood-brain barrier. When the binding and the intrinsic efficacy of these phenylhomopiperazines was compared to those of previously published phenylpiperazine analogues, it was found that (a) affinity at D-2 and D-3 dopamine receptors generally decreased, (b) the D-3 receptor binding selectivity (D-2:D-3 K-i value ratio) decreased and, (c) the intrinsic efficacy, measured using a forskolin-dependent adenylyl cyclase inhibition assay, generally increased. (C) 2013 Elsevier Ltd. All rights reserved.