7-chloro-5-phenyl-2,3-dihydro-1,4-benzoxazepine | 29165-23-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 7-chloro-5-phenyl-2,3-dihydro-1,4-benzoxazepine
• 英文别名: 7-chloro-5-phenyl-2,3-dihydrobenzo[f][1,4]oxazepine；7-chloro-2,3-dihydro-5-phenyl-1,4-benzoxazepine
• CAS: 29165-23-9
• 化学式: C₁₅H₁₂ClNO
• 分子量: 257.719
• InChiKey: CSNZXRSYGRFNFS-UHFFFAOYSA-N

物化性质

• 沸点：
  377.1±42.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  21.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-chloro-5-phenyl-2,3-dihydro-1,4-benzoxazepine 在 palladium on activated charcoal 氢气 、 N,N-Bis<2-oxo-3-oxazolidinyl>phosphorodiamidic acid 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 20.0~60.0 ℃ 、709.27 kPa 条件下， 生成 (+/-)-(1S*,9bS*)-1-hydroxy-9b-phenyl-1,3,4,9b-tetrahydro-5-oxa-2a-aza-benzo[a]cyclobuta[c]cyclo-hepten-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
• 作为产物：
  描述：

  5-氯-2-羟基二苯甲酮 在 盐酸 、 lithium aluminium tetrahydride 、 potassium carbonate 、 对甲苯磺酸 、 potassium iodide 作用下， 以 吡啶 、 乙醚 、 苯 为溶剂， 反应 33.5h， 生成 7-chloro-5-phenyl-2,3-dihydro-1,4-benzoxazepine
  参考文献：
  名称：

  Bremner, John B.; Browne, Elaine J.; Gunawardana, Indrani W. K., Australian Journal of Chemistry, 1984, vol. 37, # 1, p. 129 - 141

  摘要：

  DOI：

文献信息

• 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。
• Substituted 5-phenyl-2,3,4,5-tetrahydro-1,4-benzoxazepines
  申请人：Bristol-Myers Company

  公开号：US04125538A1

  公开（公告）日：1978-11-14

  Substituted 5-phenyl-2,3,4,5-tetrahydro-1,4-benzoxazepines of the formula ##STR1## wherein R.sup.1 and R.sup.2 are each methyl or, when taken together with the nitrogen to which they are attached, represent pyrrolidino, R.sup.3 and R.sup.4 are the same or different and represent hydrogen, chloro, fluoro, bromo, iodo, nitro, (lower)alkyl, trifluoromethyl, (lower)alkoxy, trifluoromethoxy or (lower)alkylthio, and n is an integer from 1 to 4, and their nontoxic pharmaceutically acceptable acid addition salts, are valuable analgesic and/or antitussive agents.

  公式为##STR1##的5-苯基-2,3,4,5-四氢-1,4-苯并噁唑啉的替代物，其中R.sup.1和R.sup.2分别为甲基或与它们连接的氮一起表示吡咯烷基，R.sup.3和R.sup.4相同或不同，表示氢，氯，氟，溴，碘，硝基，(较低)烷基，三氟甲基，(较低)烷氧基，三氟甲氧基或(较低)烷基硫基，n为1到4的整数，以及它们的无毒药学上可接受的酸加盐，是有价值的镇痛和/或止咳药物。
• BREMNER, J. B.;BROWNE, E. J.;GUNAWARDANA, I. W. K., AUSTRAL. J. CHEM., 1984, 37, N 1, 129-141
  作者：BREMNER, J. B.、BROWNE, E. J.、GUNAWARDANA, I. W. K.

  DOI：——

  日期：——
• US4125538A
  申请人：——

  公开号：US4125538A

  公开（公告）日：1978-11-14
• US7238685B2
  申请人：——

  公开号：US7238685B2

  公开（公告）日：2007-07-03