3-[2-(aminomethyl)phenyl]-N-(cyclopropylmethyl)pyridine-2-carboxamide | 434320-03-3

• 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: 3-[2-(aminomethyl)phenyl]-N-(cyclopropylmethyl)pyridine-2-carboxamide
• CAS: 434320-03-3
• 化学式: C₁₇H₁₉N₃O
• 分子量: 281.357
• InChiKey: YPZIELZILRQKEL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-α-methylbenzyl N-succinimidocarbonate 、 3-[2-(aminomethyl)phenyl]-N-(cyclopropylmethyl)pyridine-2-carboxamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 {2-[2-(Cyclopropylmethyl-carbamoyl)-pyridin-3-yl]-benzyl}-carbamic acid 1-phenyl-ethyl ester
  参考文献：
  名称：

  Identification, Synthesis, and Activity of Novel Blockers of the Voltage-Gated Potassium Channel Kv1.5

  摘要：

  The voltage-gated potassium channel Kv1.5 is regarded as a promising target for the development of new atrial selective drugs with fewer side effects. In the present study the discovery of ortho,ortho-disubstituted bisaryl compounds as blockers of the Kv1.5 channel is presented. Several compounds of this new class were synthesized and screened for their ability to block Kv1.5 channels expressed in Xenopus oocytes. The observed structure-activity relationship (SAR) is described by a pharmacophore model that consists of three hydrophobic centers in a triangular arrangement. The hydrophobic centers are matched by a phenyl or pyridyl ring of the bisaryl core and both ends of the side chains. The most potent compounds (e.g., 17c and 17o) inhibited the Kv1.5 channel with sub-micromolar half-blocking concentrations and displayed 3-fold selectivity over Kv1.3 and no significant effect on the HERG channel and sodium currents. In addition, compounds 17c and 17m have already shown antiarrhythmic effects in a pig model.

  DOI：

  10.1021/jm0210461
• 作为产物：
  描述：

  N-(叔丁氧羰基)-2-溴苄胺 在 四(三苯基膦)钯 、 sodium carbonate 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 二氯甲烷 为溶剂， 反应 21.0h， 生成 3-[2-(aminomethyl)phenyl]-N-(cyclopropylmethyl)pyridine-2-carboxamide
  参考文献：
  名称：

  Identification, Synthesis, and Activity of Novel Blockers of the Voltage-Gated Potassium Channel Kv1.5

  摘要：

  The voltage-gated potassium channel Kv1.5 is regarded as a promising target for the development of new atrial selective drugs with fewer side effects. In the present study the discovery of ortho,ortho-disubstituted bisaryl compounds as blockers of the Kv1.5 channel is presented. Several compounds of this new class were synthesized and screened for their ability to block Kv1.5 channels expressed in Xenopus oocytes. The observed structure-activity relationship (SAR) is described by a pharmacophore model that consists of three hydrophobic centers in a triangular arrangement. The hydrophobic centers are matched by a phenyl or pyridyl ring of the bisaryl core and both ends of the side chains. The most potent compounds (e.g., 17c and 17o) inhibited the Kv1.5 channel with sub-micromolar half-blocking concentrations and displayed 3-fold selectivity over Kv1.3 and no significant effect on the HERG channel and sodium currents. In addition, compounds 17c and 17m have already shown antiarrhythmic effects in a pig model.

  DOI：

  10.1021/jm0210461

文献信息

• Ortho, ortho-substituted nitrogen-containing bisaryl compounds, processes for their preparation, their use as medicaments, and pharmaceutical preparation comprising them
  申请人：——

  公开号：US20030060470A1

  公开（公告）日：2003-03-27

  Ortho, ortho-substituted nitrogen-containing bisaryl compounds, processes for their preparation, their use as medicaments, and pharmaceutical preparations including their use as antiarrhythmic active compounds, for example, for the treatment and prophylaxis of atrial arrhythmias, e.g. atrial fibrillation (AF) or atrial flutters. Compounds of the invention include compounds of the formula I 1

  本发明涉及一种Ortho，ortho-取代含氮双芳基化合物，其制备过程，其用作药物以及包括其用作抗心律失常活性化合物的制药制剂，例如，用于治疗和预防心房心律失常，例如心房颤动（AF）或心房扑动。本发明的化合物包括式I1的化合物。
• US6794377B2
  申请人：——

  公开号：US6794377B2

  公开（公告）日：2004-09-21
• Identification, Synthesis, and Activity of Novel Blockers of the Voltage-Gated Potassium Channel Kv1.5
  作者：Stefan Peukert、Joachim Brendel、Bernard Pirard、Andrea Brüggemann、Peter Below、Heinz-Werner Kleemann、Horst Hemmerle、Wolfgang Schmidt

  DOI：10.1021/jm0210461

  日期：2003.2.1

  The voltage-gated potassium channel Kv1.5 is regarded as a promising target for the development of new atrial selective drugs with fewer side effects. In the present study the discovery of ortho,ortho-disubstituted bisaryl compounds as blockers of the Kv1.5 channel is presented. Several compounds of this new class were synthesized and screened for their ability to block Kv1.5 channels expressed in Xenopus oocytes. The observed structure-activity relationship (SAR) is described by a pharmacophore model that consists of three hydrophobic centers in a triangular arrangement. The hydrophobic centers are matched by a phenyl or pyridyl ring of the bisaryl core and both ends of the side chains. The most potent compounds (e.g., 17c and 17o) inhibited the Kv1.5 channel with sub-micromolar half-blocking concentrations and displayed 3-fold selectivity over Kv1.3 and no significant effect on the HERG channel and sodium currents. In addition, compounds 17c and 17m have already shown antiarrhythmic effects in a pig model.