8-methoxy-1-methyl-5-phenyl-1,3-dihydrobenzo[e][1,4]diazepin-2-one | 132522-16-8

• 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: 8-methoxy-1-methyl-5-phenyl-1,3-dihydrobenzo[e][1,4]diazepin-2-one
• 英文别名: 8-methoxy-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one；8-Methoxy-1-methyl-5-phenyl-1,3-dihydro-benzo[e][1,4]diazepin-2-one；8-methoxy-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one
• CAS: 132522-16-8
• 化学式: C₁₇H₁₆N₂O₂
• 分子量: 280.326
• InChiKey: GVWCSZJBGUTVJA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  41.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-methoxy-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)-8-methoxy-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-氨基-4-甲氧基硝基苯 在 吡啶 、 sodium hydride 、 magnesium 作用下， 以 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 8-methoxy-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。
• 1,7-anellierte 1H-Indol-2-carbonsäure-N-(1,4-benzodiazepin-3-yl)amide
  申请人：Kali-Chemie Pharma GmbH

  公开号：EP0387618A1

  公开（公告）日：1990-09-19

  Es werden Verbindungen der allgemeinen Formel I beschrieben, worin R¹ Wasserstoff, niederes Alkyl oder Cycloalkylalkyl mit 4-7 Kohlenstoffatomen bedeutet, R² Wasserstoff, Halogen, niederes Alkyl, niederes Alkoxy oder Trifluormethyl bedeutet und R³ Wasserstoff, Halogen, niederes Alkyl oder niederes Alkoxy bedeutet oder R² und R³ gemeinsam eine Alkylendioxygruppe bedeuten, R⁴ Cycloalkyl mit 5 bis 6 Kohlenstoffatomen, Thiophen oder gegebenenfalls substituiertes Phenyl bedeutet, R⁵ Wasserstoff oder Halogen bedeutet, R⁶ Wasserstoff, Halogen, niederes Alkyl, niederes Alkoxy oder Trifluormethyl bedeutet und Z für eine Alkylenkette mit 2-4 Kohlenstoffatomen, welche gegebenenfalls durch niederes Alkyl mono-oder disubstituiert sein kann oder an welche gegebenenfalls ein 5-6-gliedriger carbocyclischer Ring anelliert sein kann, oder für eine -X-CH₂-CH₂-kette steht. Die Verbindungen besitzen pharmakologisch wertvolle Eigen­schaften.

  所述化合物的通式为 I 其中 R¹ 是氢、低级烷基或具有 4-7 个碳原子的环烷基烷基、 R² 是氢、卤素、低级烷基、低级烷氧基或三氟甲基，以及 R³ 表示氢、卤素、低级烷基或低级烷氧基，或 R² 和 R³ 共同表示烷二氧基、 R⁴ 表示具有 5-6 个碳原子的环烷基、噻吩或任选取代的苯基、 R⁵ 表示氢或卤素、 R⁶ 表示氢、卤素、低级烷基、低级烷氧基或三氟甲基，以及 Z 是含有 2-4 个碳原子的亚烷基链、 Z 是具有 2-4 个碳原子的亚烷基链，可选择由低级烷基单取代或二取代，或可选择与 5-6 元碳环融合，或代表-X-CH₂-CH₂链。 这些化合物具有宝贵的药理特性。
• Structure-activity relationship of BMS906024 derivatives for Cryptosporidium parvum growth inhibition
  作者：Seungheon Lee、Melissa S. Love、Ramkumar Modukuri、Arnab K. Chatterjee、Lauren Huerta、Ann P. Lawson、Case W. McNamara、Jan R. Mead、Lizbeth Hedstrom、Gregory D. Cuny

  DOI：10.1016/j.bmcl.2023.129328

  日期：2023.6
• 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