N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichlorobenzamide | 1416984-93-4

• 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: N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichlorobenzamide
• 英文别名: Cav 3.2 inhibitor 4；N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)piperidin-4-yl]methyl]-3,5-dichlorobenzamide
• CAS: 1416984-93-4
• 化学式: C₂₁H₃₂Cl₂N₄O₃
• 分子量: 459.416
• InChiKey: RAZOFRCGTLUGNK-UHFFFAOYSA-N

物化性质

• 沸点：
  637.6±55.0 °C(Predicted)
• 密度：
  1.211±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  93.7
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-叔丁基4-乙基4-氰基哌啶-1,4-二羧酸 在 吡啶 、 盐酸 、 sodium tetrahydroborate 、 氨 、 氢气 、 potassium carbonate 、 乙酰氯 、 sodium iodide 、 sodium hydroxide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichlorobenzamide
  参考文献：
  名称：

  Discovery of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide as a selective T-type calcium channel (Cav3.2) inhibitor

  摘要：

  The T-type calcium channel inhibitor Mibefradil was reported to protect the heart from atrial remodeling, a key process involved in the development of atrial fibrillation and arrhythmias. Mibefradil is not a selective T-type calcium channel inhibitor and also affects the function of different ion channels. Our aim was to develop a selective T-type calcium channel inhibitor to validate the importance of T-type-related pharmacology in atrial fibrillation. Structural optimisation of a previously disclosed hit series focussed on minimising exposure to the central nervous system and improving pharmacokinetic properties, while maintain adequate potency and selectivity. This resulted in the design of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide, a novel, selective, peripherally restricted chemical probe to verify the role of T-type calcium channel inhibition on atrial fibrillation protection. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.140

文献信息

• Discovery of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide as a selective T-type calcium channel (Cav3.2) inhibitor
  作者：Fabrizio Giordanetto、Andreas Wållberg、Laurent Knerr、Nidhal Selmi、Victoria Ullah、Fredrik Thorstensson、Åsa Lindelöf、Staffan Karlsson、Grigorios Nikitidis、Antonio Llinas、Qing-Dong Wang、Anders Lindqvist、Ågot Högberg、Emma Lindhardt、Annika Åstrand、Göran Duker

  DOI：10.1016/j.bmcl.2012.10.140

  日期：2013.1

  The T-type calcium channel inhibitor Mibefradil was reported to protect the heart from atrial remodeling, a key process involved in the development of atrial fibrillation and arrhythmias. Mibefradil is not a selective T-type calcium channel inhibitor and also affects the function of different ion channels. Our aim was to develop a selective T-type calcium channel inhibitor to validate the importance of T-type-related pharmacology in atrial fibrillation. Structural optimisation of a previously disclosed hit series focussed on minimising exposure to the central nervous system and improving pharmacokinetic properties, while maintain adequate potency and selectivity. This resulted in the design of N-[[1-[2-(tert-butylcarbamoylamino)ethyl]-4-(hydroxymethyl)-4-piperidyl]methyl]-3,5-dichloro-benzamide, a novel, selective, peripherally restricted chemical probe to verify the role of T-type calcium channel inhibition on atrial fibrillation protection. (C) 2012 Elsevier Ltd. All rights reserved.