acetic acid 2-(2-oxo-5-phenyl-2,3-dihydrobenzo[e][1,4]diazepin-1-yl)ethyl ester | 159586-66-0

• 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: acetic acid 2-(2-oxo-5-phenyl-2,3-dihydrobenzo[e][1,4]diazepin-1-yl)ethyl ester
• 英文别名: Acetic acid 2-(2-oxo-5-phenyl-2,3-dihydro-benzo[e][1,4]diazepin-1-yl)-ethyl ester；2-(2-oxo-5-phenyl-3H-1,4-benzodiazepin-1-yl)ethyl acetate
• CAS: 159586-66-0
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: AJFVULAMBWIJFM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  59
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  acetic acid 2-(2-oxo-5-phenyl-2,3-dihydrobenzo[e][1,4]diazepin-1-yl)ethyl ester 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 60.0 ℃ 、709.27 kPa 条件下， 生成 rac-(SR)-(4,6-dimethylpyrimidin-2-yloxy)-[(5SR)-1-(2-hydroxyethyl)-2-oxo-5-phenyl-2,3,4,5-tetrahydro-1H-benzo[e][1,4]diazepin-5-yl]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-溴乙基乙酸酯 、 1,3-二氢-5-苯基-1,4-苯并二氮杂卓-2-酮 以to give acetic acid 2-(2-oxo-5-phenyl-2,3-dihydro-benzo[e][1,4]diazepin-1-yl)-ethyl ester (4.0 g) as a pale yellow oil的产率得到acetic acid 2-(2-oxo-5-phenyl-2,3-dihydrobenzo[e][1,4]diazepin-1-yl)ethyl ester
  参考文献：
  名称：

  Novel benzo-fused heterocycles as endothelin antagonisits

  摘要：

  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。

  公开号：

  US20050124605A1

文献信息

• US7238685B2
  申请人：——

  公开号：US7238685B2

  公开（公告）日：2007-07-03
• [EN] NOVEL BENZO-FUSED HETEROCYCLES AS ENDOTHELIN ANTAGONISITS<br/>[FR] HETEROCYCLES A FUSION BENZO UTILISES COMME ANTAGONISTES VIS-A-VIS DE L'ENDOTHELINE
  申请人：ACTELION PHARMACEUTICALS LTD

  公开号：WO2003013545A1

  公开（公告）日：2003-02-20

  The invention relates to novel benzo-fused heterocycles of structure (I) 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. Formula (I)