S 9947

• 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: S 9947
• 英文别名: N-(2-(2-pyridyl)ethyl)-2'-(benzyloxycarbonylaminomethyl)bi-phenyl-2-carboxamide；2'-(benzyloxycarbonylaminomethyl)biphenyl-2-carboxylic acid 2-(2-pyridyl)-ethylamide；2'-(benzyloxycarbonylaminomethyl)biphenyl-2-carboxylic acid 2-(pyridin-2-yl)-ethylamide；2'-(Benzyloxycarbonylaminomethyl)biphenyl-2-carboxylic acid 2-(2-pyridyl)ethylamide；benzyl N-[[2-[2-(2-pyridin-2-ylethylcarbamoyl)phenyl]phenyl]methyl]carbamate
• 化学式: C₂₉H₂₇N₃O₃
• 分子量: 465.552
• InChiKey: FLOLVFLAXFXKBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  80.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2'-(phthalimidomethyl)biphenyl-2-carboxylic acid 在 碳酸氢钠 、 1-羟基苯并三唑 、 一水合肼 、 N,N'-二异丙基碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 17.5h， 生成 S 9947
  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
• 作为试剂：
  描述：

  2-(2-氨乙基)吡啶 、 2'-(benzyloxycarbonylaminomethyl)biphenyl-2-carboxylic acid 在 S 9947 作用下， 以 ethyl acetate heptane 为溶剂， 生成 S 9947
  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：

  公式为I,1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)的含义如权利要求所示，非常适用于作为新型和抗心律失常活性化合物，特别适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：

  US20040102513A1

文献信息

• Combination of phenylcarboxylic acid amides with beta-adrenoreceptor blockers and their use for the treatment of atrial arrhythmias
  申请人：Wirth Klaus

  公开号：US20050054673A1

  公开（公告）日：2005-03-10

  The invention relates to the combination of one or more beta-blockers and of one or more Kv1.5 blockers, in particular phenylcarboxamides of the formula la and/or lb and/or physiologically tolerable salts thereof, and the use of the combination for the treatment or prophylaxis of atrial arrhythmias.

  该发明涉及一种或多种β受体阻滞剂与一种或多种Kv1.5通道阻滞剂的组合，特别是公式la和/或lb和/或其生理耐受盐，以及利用该组合物治疗或预防心房心律失常。
• Kv1.5-BLOCKER FOR THE SELECTIVE INCREASE OF ATRIAL CONTRACTILITY AND TREATMENT OF CARDIAC INSUFFICIENCY
  申请人：WIRTH Klaus

  公开号：US20070043091A1

  公开（公告）日：2007-02-22

  The invention relates to the atrial contractility-increasing effect of Kv1.5 blockers, especially phenylcarboxamides of the formulae Ia or Ib or pharmaceutically acceptable salts thereof, for treating reduced atrial contractility and heart failure, especially heart failure caused by diastolic dysfunction.

  该发明涉及Kv1.5阻滞剂，特别是式Ia或Ib的苯基羧酰胺类药物可接受的盐，用于治疗降低心房收缩力和心力衰竭，特别是由舒张功能障碍引起的心力衰竭的心房收缩力增加作用。
• 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。
• [DE] KOMBINATION VON PHENYLCARBONSÄUREAMIDEN MIT BLOCKERN DES IKr-KANALS UND DEREN VERWENDUNG ZUR BEHANDLUNG VON VORHOFARRHYTHMIEN<br/>[EN] PHENYLCARBOXYL ACID AMIDES AND IKr CHANNEL INHIBITORS COMBINATION AND THE USE THEREOF FOR TREATING ATRIAL ARRHYTHMIA<br/>[FR] ASSOCIATION D'AMIDES DE L'ACIDE PHENYLCARBOXYLIQUE ET D'INHIBITEURS DU CANAL IKR ET UTILISATION DE CETTE ASSOCIATION POUR TRAITER DES ARYTHMIES ATRIALES
  申请人：AVENTIS PHARMA GMBH

  公开号：WO2004082716A1

  公开（公告）日：2004-09-30

  Die Erfindung betrifft die Kombination aus einem oder mehreren IKr-Kanal-Blockern und aus einem oder mehreren Kv1.5-Blockern, insbesondere Phenylcarbonsäureamiden der Formel (Ia) und/oder (Ib) und/oder pharmazeutisch verträglichen Salzen davon, und die Verwendung der Kombination zur Behandlung von Vorhofarrhythmien.

  这项发明涉及一种将一个或多个IKr通道阻滞剂与一个或多个Kv1.5通道阻滞剂结合的组合物，特别是公式（Ia）和/或（Ib）的苯基羧酸酰胺及/或其药学上可接受的盐，以及该组合物在房颤治疗中的应用。
• 2'-substituted 1,1'-biphenyl-2-carboxamides, process for their preparation, their use as medicaments, and pharmaceutical preparations comprising them
  申请人：Aventis Pharma Deutschland GmbH

  公开号：US20030171351A1

  公开（公告）日：2003-09-11

  Compounds of the formula I, 1 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.

  化学式为I,1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)的含义如权利要求中所示，非常适用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。