[2'-(2,4-difluorobenzylcarbamoyl)biphenyl-2-ylmethyl]carbamic acid tert-butyl ester | 498577-62-1

• 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: [2'-(2,4-difluorobenzylcarbamoyl)biphenyl-2-ylmethyl]carbamic acid tert-butyl ester
• 英文别名: 2'-(tert-butoxycarbonylaminomethyl)biphenyl-2-carboxylic acid (2,4-difluorobenzyl)amide；tert-butyl N-[[2-[2-[(2,4-difluorophenyl)methylcarbamoyl]phenyl]phenyl]methyl]carbamate
• CAS: 498577-62-1
• 化学式: C₂₆H₂₆F₂N₂O₃
• 分子量: 452.501
• InChiKey: LZMFNRJBIRFTSN-UHFFFAOYSA-N

物化性质

• 沸点：
  637.5±55.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  [2'-(2,4-difluorobenzylcarbamoyl)biphenyl-2-ylmethyl]carbamic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 2'-Aminomethylbiphenyl-2-carboxylic acid (2,4-di-fluorobenzyl)amide
  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：

  2'-(tert-butoxycarbonylaminomethyl)biphenyl-2-carboxylic acid 生成 [2'-(2,4-difluorobenzylcarbamoyl)biphenyl-2-ylmethyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  2′-Substituted 1,1′-biphenyl-2-carboxamides, processes for their preparation, their use as medicaments, and pharmaceutical preparations comprising them

  摘要：

  公式I中的化合物，其中R（1），R（2），R（3），R（4），R（5），R（6），R（7），R（8），R（30）和R（31）具有声明中指定的含义，非常适合作为新的抗心律失常活性化合物，特别是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。

  公开号：

  US06531495B1

文献信息

• 2'-Substituted 1,1'-Biphenyl-2-Carboxamides, Processes For Their Preparation, Their Use As Medicaments, And Pharmaceutical Preparations Comprising Them
  申请人：BRENDEL Joachim

  公开号：US20090192096A1

  公开（公告）日：2009-07-30

  Compounds of the formula I, in which R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30) and R(31) have the meanings indicated in the claims, are very particularly suitable as novel and antiarrythmic active compounds, in particular for the treatment and prophylaxis of atrial arrythmias, e.g. atrial fibrillation (AF), or atrial flutter.

  公式I的化合物中，R（1）、R（2）、R（3）、R（4）、R（5）、R（6）、R（7）、R（8）、R（30）和R（31）具有所述要求中所示的含义，特别适用于作为新型和抗心律失常活性化合物，特别是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。
• US7514582B2
  申请人：——

  公开号：US7514582B2

  公开（公告）日：2009-04-07
• US7982045B2
  申请人：——

  公开号：US7982045B2

  公开（公告）日：2011-07-19
• 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.
• 2′-Substituted 1,1′-biphenyl-2-carboxamides, processes for their preparation, their use as medicaments, and pharmaceutical preparations comprising them
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US06531495B1

  公开（公告）日：2003-03-11

  Compounds of the formula I, in which R(1), R(2), R(3), R(4), R(5), R(6), R(7), R(8), R(30) and R(31) have the meanings indicated in the claims, are very particularly suitable as novel and antiarrythmic active compounds, in particular for the treatment and prophylaxis of atrial arrythmias, e.g. atrial fibrillation (AF), or atrial flutter.

  公式I中的化合物，其中R（1），R（2），R（3），R（4），R（5），R（6），R（7），R（8），R（30）和R（31）具有声明中指定的含义，非常适合作为新的抗心律失常活性化合物，特别是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。