3-((7aS,8S,11aS,11bR)-9,11b-Dimethyl-3,11-dioxo-2,3,4,6,7,7a,8,11,11a,11b-decahydro-1H-naphtho[2,1-c]azepin-8-yl)propanenitrile | 1422160-57-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: 3-((7aS,8S,11aS,11bR)-9,11b-Dimethyl-3,11-dioxo-2,3,4,6,7,7a,8,11,11a,11b-decahydro-1H-naphtho[2,1-c]azepin-8-yl)propanenitrile
• 英文别名: 3-[(7aS,8S,11aS,11bR)-9,11b-dimethyl-3,11-dioxo-1,2,4,6,7,7a,8,11a-octahydrobenzo[g][2]benzazepin-8-yl]propanenitrile
• CAS: 1422160-57-3
• 化学式: C₁₉H₂₄N₂O₂
• 分子量: 312.412
• InChiKey: VSOPSMFWKLBEDW-OHQAAIJDSA-N

物化性质

• 沸点：
  580.1±50.0 °C(predicted)
• 密度：
  1.16±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  70
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-((7aS,8S,11aS,11bR)-9,11b-Dimethyl-3,11-dioxo-2,3,4,6,7,7a,8,11,11a,11b-decahydro-1H-naphtho[2,1-c]azepin-8-yl)propanenitrile 、 2-氯苄溴 在 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 16.5h， 以5%的产率得到3-((7aS,8S,11aS,11bR)-4-(2-Chlorobenzyl)-9,11b-dimethyl-3,11-dioxo-2,3,4,6,7,7a,8,11,11a,11b-decahydro-1H-naphtho[2,1-c]azepin-8-yl)propanenitrile
  参考文献：
  名称：

  COMPLEX AND STRUCTURALLY DIVERSE COMPOUNDS

  摘要：

  这项发明提供了一种新颖、通用且简便的策略，用于创造具有高结构和立体化学复杂性的小分子。该方法的方面包括系统地应用于快速将易得的天然产物转化为具有多样分子结构的结构复杂化合物的环系统失真反应。通过评估化学性质，包括sp3碳的分数、ClogP和立体中心的数量，这些化合物被证明比标准筛选集合中的化合物显着更复杂和多样化。这种方法是通过来自三个不同结构类别的天然产物（赤霉酸、肾上腺酮和奎宁）来展示的，并描述了将该策略应用于任何合适的天然产物的方法。

  公开号：

  US20150274638A1
• 作为产物：
  描述：

  肾上腺甾酮 在 sodium azide 、 硫酸 作用下， 反应 1.0h， 以28%的产率得到3-((7aS,8S,11aS,11bR)-9,11b-Dimethyl-4,11-dioxo-2,3,4,6,7,7a,8,11,11a,11b-decahydro-1H-naphtho[1,2-d]azepin-8-yl)propanenitrile
  参考文献：
  名称：

  A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products

  摘要：

  高通量筛选是药物发现过程中确定先导化合物的主要方法。因此，筛选库的组成在很大程度上决定了可调节的生物靶点和可开发的治疗方法。遗憾的是，大多数化合物筛选库主要由结构或立体化学复杂性较低的平面分子组成，这些化合物无法提供调节许多药物靶点所需的化学功能排列。在这里，我们介绍了一种新颖、通用和简便的策略，即利用现成的天然产物作为合成起点，创造出具有高结构和立体化学复杂性的多种化合物。我们通过对化学性质（包括 sp3 碳的比例、ClogP 和立体中心的数量）的评估表明，这些化合物的复杂性和多样性明显高于标准筛选集合中的化合物。本文介绍了一种构建复杂多样化合物库的方法，即通过一系列环系统畸变反应改变天然产物。生成的化合物与标准筛选库中的化合物具有明显不同的理化性质，因此在寻找可开发成候选药物的先导分子方面具有优势。

  DOI：

  10.1038/nchem.1549

文献信息

• Complex and structurally diverse compounds
  申请人：The Board of Trustees of the University of Illinois

  公开号：US10800730B2

  公开（公告）日：2020-10-13

  The invention provides a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.

  本发明提供了一种新颖、通用和简便的策略，用于制造具有高结构和立体化学复杂性的小分子。该方法的各个方面包括系统地应用环系畸变反应，将容易获得的天然产物快速转化为具有不同分子结构的结构复杂的化合物。通过对化学特性（包括 sp3 碳的比例、ClogP 和立体中心的数量）进行评估，这些化合物的复杂性和多样性明显高于标准筛选集合中的化合物。该方法通过三种不同结构类别的天然产物（赤霉素、肾上腺甾酮和奎宁）进行了演示，并介绍了将该策略应用于任何合适的天然产物的方法。
• Target-Agnostic P-Glycoprotein Assessment Yields Strategies to Evade Efflux, Leading to a BRAF Inhibitor with Intracranial Efficacy
  作者：Aya M. Kelly、Matthew R. Berry、Sarah Z. Tasker、Sydney A. McKee、Timothy M. Fan、Paul J. Hergenrother

  DOI：10.1021/jacs.2c03944

  日期：2022.7.13
• [EN] COMPLEX AND STRUCTURALLY DIVERSE COMPOUNDS<br/>[FR] COMPOSÉS COMPLEXES ET DE STRUCTURES DIVERSES
  申请人：HERGENROTHER PAUL J

  公开号：WO2013142873A2

  公开（公告）日：2013-09-26

  The invention provides a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.
• COMPLEX AND STRUCTURALLY DIVERSE COMPOUNDS
  申请人：The Board of Trustees of the University of Illinois

  公开号：US20150274638A1

  公开（公告）日：2015-10-01

  The invention provides a novel, general, and facile strategy for the creation of small molecules with high structural and stereochemical complexity. Aspects of the methods include ring system distortion reactions that are systematically applied to rapidly convert readily available natural products to structurally complex compounds with diverse molecular architectures. Through evaluation of chemical properties including fraction of sp 3 carbons, ClogP, and the number of stereogenic centers, these compounds are shown to be significantly more complex and diverse than those in standard screening collections. This approach is demonstrated with natural products (gibberellic acid, adrenosterone, and quinine) from three different structural classes, and methods are described for the application of this strategy to any suitable natural product.

  这项发明提供了一种新颖、通用且简便的策略，用于创造具有高结构和立体化学复杂性的小分子。该方法的方面包括系统地应用于快速将易得的天然产物转化为具有多样分子结构的结构复杂化合物的环系统失真反应。通过评估化学性质，包括sp3碳的分数、ClogP和立体中心的数量，这些化合物被证明比标准筛选集合中的化合物显着更复杂和多样化。这种方法是通过来自三个不同结构类别的天然产物（赤霉酸、肾上腺酮和奎宁）来展示的，并描述了将该策略应用于任何合适的天然产物的方法。
• A ring-distortion strategy to construct stereochemically complex and structurally diverse compounds from natural products
  作者：Robert W. Huigens III、Karen C. Morrison、Robert W. Hicklin、Timothy A. Flood Jr、Michelle F. Richter、Paul J. Hergenrother

  DOI：10.1038/nchem.1549

  日期：2013.3

  High-throughput screening is the dominant method used to identify lead compounds in drug discovery. As such, the makeup of screening libraries largely dictates the biological targets that can be modulated and the therapeutics that can be developed. Unfortunately, most compound-screening collections consist principally of planar molecules with little structural or stereochemical complexity, compounds that do not offer the arrangement of chemical functionality necessary for the modulation of many drug targets. Here we describe a novel, general and facile strategy for the creation of diverse compounds with high structural and stereochemical complexity using readily available natural products as synthetic starting points. We show through the evaluation of chemical properties (which include fraction of sp3 carbons, ClogP and the number of stereogenic centres) that these compounds are significantly more complex and diverse than those in standard screening collections, and we give guidelines for the application of this strategy to any suitable natural product. An approach for the construction of complex and diverse compound libraries is described, whereby natural products are altered through a series of ring system distortion reactions. The compounds produced have markedly different physiochemical properties from those in standard screening collections and thus could offer advantages in the search for lead molecules that can be developed into drug candidates.

  高通量筛选是药物发现过程中确定先导化合物的主要方法。因此，筛选库的组成在很大程度上决定了可调节的生物靶点和可开发的治疗方法。遗憾的是，大多数化合物筛选库主要由结构或立体化学复杂性较低的平面分子组成，这些化合物无法提供调节许多药物靶点所需的化学功能排列。在这里，我们介绍了一种新颖、通用和简便的策略，即利用现成的天然产物作为合成起点，创造出具有高结构和立体化学复杂性的多种化合物。我们通过对化学性质（包括 sp3 碳的比例、ClogP 和立体中心的数量）的评估表明，这些化合物的复杂性和多样性明显高于标准筛选集合中的化合物。本文介绍了一种构建复杂多样化合物库的方法，即通过一系列环系统畸变反应改变天然产物。生成的化合物与标准筛选库中的化合物具有明显不同的理化性质，因此在寻找可开发成候选药物的先导分子方面具有优势。