5-(3-Fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one | 713517-44-3

• 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: 5-(3-Fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 713517-44-3
• 化学式: C₁₅H₁₁FN₂O
• 分子量: 254.264
• InChiKey: ZNGUINVPFNQZKG-UHFFFAOYSA-N

物化性质

• 沸点：
  427.8±45.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(3-Fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-2-one 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 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， 反应 16.0h， 生成
  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：

  间溴氟苯 在 氨 、 水 、 magnesium 作用下， 以 甲醇 、 乙醚 、 二氯甲烷 为溶剂， 生成 5-(3-Fluorophenyl)-1,3-dihydro-1,4-benzodiazepin-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

• COMPOUNDS FOR INHIBITING BETA-AMYLOID PEPTIDE RELEASE AND/OR ITS SYNTHESIS
  申请人：Elan Pharmaceuticals, Inc.

  公开号：EP1089977A1

  公开（公告）日：2001-04-11
• [EN] COMPOUNDS FOR INHIBITING BETA-AMYLOID PEPTIDE RELEASE AND/OR ITS SYNTHESIS<br/>[FR] COMPOSES DESTINES A INHIBER LA LIBERATION ET/OU LA SYNTHESE DU PEPTIDE BETA-AMYLOIDE
  申请人：ELAN PHARMACEUTICALS, INC.

  公开号：WO1999067219A1

  公开（公告）日：1999-12-29

  (EN) Compounds of formula (I), wherein $i(W) is a cyclic group of the type (2); (3); $i(Y) is represented by the formula (II); these compounds inhibit $g(b)-amyloid peptide release and/or its synthesis, and, accordingly, have utility in treating Alzheimer's disease. Also disclosed are pharmaceutical compositions comprising a compound which inhibits $g(b)-amyloid peptide release and/or its synthesis as well as methods for treating Alzheimer's disease both prophylactically and therapeutically with such pharmaceutical compositions.(FR) L'invention concerne des composés représentés par la formule (I): dans laquelle $i(W) représente un groupe cyclique du type (2); (3); et $i(Y) est représenté par la formule (II). Ces composés inhibent la libération et/ou la synthèse du peptide bêta-amyloïde, et sont donc utiles dans le traitement de la maladie d'Alzheimer. L'invention concerne également des compositions pharmaceutiques comprenant un composé qui inhibe la libération et/ou la synthèse du peptide bêta-amyloïde, ainsi que des méthodes de traitement de la maladie d'Alzheimer, de manière thérapeutique et prophylactique, à l'aide desdites compositions pharmaceutiques.