5-<3-Trifluormethyl-phenyl>-1,3-dihydro-2H-1,4-benzodiazepin-2-on | 3864-49-1

• 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: 5-<3-Trifluormethyl-phenyl>-1,3-dihydro-2H-1,4-benzodiazepin-2-on
• 英文别名: 5-<3-Trifluormethyl-phenyl>-2-oxo-1.2-dihydro-1.4-benzodiazepin；5-<3-(Trifluormethyl)-phenyl>-3H-1.4-benzodiazepin-2(1H)-on；5-(3-trifluoromethyl-phenyl)-1,3-dihydro-benzo[e][1,4]diazepin-2-one；1,3-dihydro-5-(α,α,α-trifluoro-m-tolyl)-2H-1,4-benzodiazepin-2-one；5-(3-Trifluoromethylphenyl)-1,3-dihydro-benzo[e][1,4]diazepin-2-one；5-[3-(trifluoromethyl)phenyl]-1,3-dihydro-1,4-benzodiazepin-2-one
• CAS: 3864-49-1
• 化学式: C₁₆H₁₁F₃N₂O
• 分子量: 304.271
• InChiKey: RMNQMFPFGLLSPE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  41.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-<3-Trifluormethyl-phenyl>-1,3-dihydro-2H-1,4-benzodiazepin-2-on 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 (+/-)-(1S*,9bS*)-1-hydroxy-5-(4-methoxy-benzyl)-9b-(3-trifluoromethyl-phenyl)-5,9b-dihydro-1H-2a,5diazabenzo[a]cyclobuta[c]cycloheptene-2,4-dione
  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：

  间溴三氟甲苯 在 吡啶 、 magnesium 作用下， 以 乙醚 为溶剂， 生成 5-<3-Trifluormethyl-phenyl>-1,3-dihydro-2H-1,4-benzodiazepin-2-on
  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

• Isoindole derivatives as appetite suppressants
  申请人：Hoffmann-La Roche Inc.

  公开号：US03996374A1

  公开（公告）日：1976-12-07

  Isoindole derivatives of the formula ##STR1## wherein R.sub.1 -R.sub.6, A and Z are as hereinafter described. The isoindole derivatives are useful as appetite suppressants.

  公式为##STR1##的异吲哚衍生物，其中R.sub.1 -R.sub.6，A和Z如下所述。这些异吲哚衍生物可用作食欲抑制剂。
• 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。
• Isoindole derivatives
  申请人：Hoffmann-La Roche Inc.

  公开号：US04090027A1

  公开（公告）日：1978-05-16

  Isoindole derivatives of the formula ##STR1## wherein R.sub.1 -R.sub.6, A and Z are as hereinafter described. The isoindole derivatives are useful as appetite suppressants.

  公式为##STR1##的异吲哚衍生物，其中R.sub.1 -R.sub.6、A和Z如下所述。这些异吲哚衍生物可用作食欲抑制剂。
• US3996374A
  申请人：——

  公开号：US3996374A

  公开（公告）日：1976-12-07
• US4077978A
  申请人：——

  公开号：US4077978A

  公开（公告）日：1978-03-07