7,8-dimethoxy-1-methyl-5-phenyl-1,3-dihydrobenzo[e][1,4]diazepin-2-one | 477742-19-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 7,8-dimethoxy-1-methyl-5-phenyl-1,3-dihydrobenzo[e][1,4]diazepin-2-one
• 英文别名: 7,8-dimethoxy-1-methyl-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one；7,8-dimethoxy-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one
• CAS: 477742-19-1
• 化学式: C₁₈H₁₈N₂O₃
• 分子量: 310.353
• InChiKey: UHYVPWDNMXWRNH-UHFFFAOYSA-N

物化性质

• 沸点：
  535.9±50.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  7,8-dimethoxy-1-methyl-5-phenyl-1,3-dihydrobenzo[e][1,4]diazepin-2-one 在 lithium hydroxide 、 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 生成 rac-(SR)-{(5SR)-7,8-dimethoxy-1-methyl-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-5-yl}-(3,5-dimethoxyphenoxy)acetic acid
  参考文献：
  名称：

  Novel Benzo[1,4]diazepin-2-one Derivatives as Endothelin Receptor Antagonists

  摘要：

  Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiology of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan 2, are in late clinical trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan 2, we designed a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e] [1,4]diazepin-2-one scaffold. Here, we report on the preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives. Potent dual ETA/ETB receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt sensitive rats. In this animal model, the efficacy of the benzo [e] [1,4] diazepin-2-one derivative rac-39au was superior to that of racemic ambrisentan, rac-2.

  DOI：

  10.1021/jm031115r
• 作为产物：
  描述：

  (2-amino-4,5-dimethoxyphenyl)(phenyl)methanone 在 吡啶 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 7,8-dimethoxy-1-methyl-5-phenyl-1,3-dihydrobenzo[e][1,4]diazepin-2-one
  参考文献：
  名称：

  Novel Benzo[1,4]diazepin-2-one Derivatives as Endothelin Receptor Antagonists

  摘要：

  Since its discovery in 1988 by Yanagisawa et al., endothelin (ET), a potent vasoconstrictor, has been widely implicated in the pathophysiology of cardiovascular, cerebrovascular, and renal diseases. Many research groups have embarked on the discovery and development of ET receptor antagonists for the treatment of such diseases. While several compounds, e.g., ambrisentan 2, are in late clinical trials for various indications, one compound (bosentan, Tracleer) is being marketed to treat pulmonary arterial hypertension. Inspired by the structure of ambrisentan 2, we designed a novel class of ET receptor antagonists based on a 1,3,4,5-tetrahydro-1H-benzo[e] [1,4]diazepin-2-one scaffold. Here, we report on the preparation as well as the in vitro and in vivo structure-activity relationships of these derivatives. Potent dual ETA/ETB receptor antagonists with affinities in the low nanomolar range have been identified. In addition, several compounds efficiently reduced arterial blood pressure after oral administration to Dahl salt sensitive rats. In this animal model, the efficacy of the benzo [e] [1,4] diazepin-2-one derivative rac-39au was superior to that of racemic ambrisentan, rac-2.

  DOI：

  10.1021/jm031115r

文献信息

• Cyclic nucleotide phosphodiesterase inhibitors, preparation and uses thereof
  申请人：——

  公开号：US20040152888A1

  公开（公告）日：2004-08-05

  The invention concerns novel benzodiazepine derivatives and their uses in the field of therapeutics particularly for treating pathologies involving the activity of a cyclic nucleotide phosphodiesterase. It also concerns methods for preparing them and novel synthesis intermediates. The inventive compounds more particularly correspond to general formula (I): 1

  这项发明涉及新型苯二氮卓类衍生物及其在治疗领域中的用途，特别用于治疗涉及环核苷酸磷酸二酯酶活性的病理。它还涉及制备它们的方法和新型合成中间体。这些创新化合物更特别地对应于一般式(I)：1
• Novel benzo-fused heterocycles as endothelin antagonisits
  申请人：Bolli Martin

  公开号：US20050124605A1

  公开（公告）日：2005-06-09

  The invention relates to novel benzo-fused heterocycles and their use as active ingredients in the preparation of pharmaceutical compositions. The invention also concerns related aspects including processes for the preparation of the compounds, pharmaceutical compositions containing one or more of those compounds and especially their use as endothelin receptor antagonists.

  本发明涉及新型苯并杂环化合物及其用作制备药物组成物的活性成分。本发明还涉及相关方面，包括制备化合物的过程，含有其中一种或多种化合物的药物组成物，特别是它们作为内皮素受体拮抗剂的用途。
• New PDE4 inhibitors based on pharmacophoric similarity between papaverine and tofisopam
  作者：Frédéric J.J. Bihel、Hélène Justiniano、Martine Schmitt、Malik Hellal、Mohamed A. Ibrahim、Claire Lugnier、Jean-Jacques Bourguignon

  DOI：10.1016/j.bmcl.2011.08.036

  日期：2011.11

  Pharmacophoric comparison between papaverine and tofisopam led to identify three new series of micro- to sub-micromolar inhibitors of phosphodiesterase-4, including 7,8-dialkoxy-2,3-benzodiazepin-4-one derivatives, 7,8-dialkoxy-1,4-benzodiazepin-2-one derivatives, and dialkoxybenzophenone derivatives. (C) 2011 Elsevier Ltd. All rights reserved.
• INHIBITEURS DES PHOSPHODIESTERASES DES NUCLEOTIDES CYCLIQUES, PREPARATION ET UTILISATIONS DE CES INHIBITEURS
  申请人：NEURO3D

  公开号：EP1392663A2

  公开（公告）日：2004-03-03
• US7238685B2
  申请人：——

  公开号：US7238685B2

  公开（公告）日：2007-07-03