3-Methyl-4-[7-methyl-1-(1-propyl-butyl)-2,2a,3,4-tetrahydro-1H-1,5,6,8-tetraaza-acenaphthylen-5-yl]-benzonitrile | 476645-19-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-Methyl-4-[7-methyl-1-(1-propyl-butyl)-2,2a,3,4-tetrahydro-1H-1,5,6,8-tetraaza-acenaphthylen-5-yl]-benzonitrile
• 英文别名: 4-(2-Heptan-4-yl-10-methyl-2,7,9,11-tetrazatricyclo[6.3.1.04,12]dodeca-1(11),8(12),9-trien-7-yl)-3-methylbenzonitrile
• CAS: 476645-19-9
• 化学式: C₂₄H₃₁N₅
• 分子量: 389.544
• InChiKey: HSRQDPKHQTVGBX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-Methyl-4-[7-methyl-1-(1-propyl-butyl)-2,2a,3,4-tetrahydro-1H-1,5,6,8-tetraaza-acenaphthylen-5-yl]-benzonitrile 在 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 4-(2-Heptan-4-yl-10-methyl-2,7,9,11-tetrazatricyclo[6.3.1.04,12]dodeca-1(12),3,8,10-tetraen-7-yl)-3-methylbenzonitrile
  参考文献：
  名称：

  Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

  摘要：

  Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.040
• 作为产物：
  描述：

  2-(4,6-Dichloro-2-methyl-pyrimidin-5-yl)-pent-4-en-1-ol 在 咪唑 、 4-二甲氨基吡啶 、 sodium hydride 、 臭氧 、 triethylamine tris(hydrogen fluoride) 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 142.0h， 生成 3-Methyl-4-[7-methyl-1-(1-propyl-butyl)-2,2a,3,4-tetrahydro-1H-1,5,6,8-tetraaza-acenaphthylen-5-yl]-benzonitrile
  参考文献：
  名称：

  Substituted tetraazaacenaphthylenes as potent CRF1 receptor antagonists for the treatment of depression and anxiety

  摘要：

  Two isomers of the hexahydro-tetraazaacenaphthylene templates (1 and 2) are presented as novel, potent, and selective corticotropin releasing factor-1 (CRF1) receptor antagonists. In this paper, we report the affinity and SAR of a series of compounds, as well as pharmacokinetic characterization of a chosen set. The anxiolitic activity of a selected example (2ba) in the rat pup vocalization model is also presented. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.040

文献信息

• [EN] TRI-AND TETRAAZA-ACENAPHTHYLEN DERIVATIVES AS CRF RECEPTOR ANTAGONISTS<br/>[FR] DERIVES TRI- ET TETRAAZA-ACENAPHTHYLENE UTILISES COMME ANTAGONISTES DU RECEPTEUR CRF
  申请人：NEUROCRINE INC

  公开号：WO2002094826A1

  公开（公告）日：2002-11-28

  CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure of formula (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, R1, R2, R4, R5, R6, A, X, and Y are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same.

  本发明揭示了CRF受体拮抗剂，其在治疗多种疾病方面具有用途，包括治疗温血动物中CRF过度分泌表现的疾病，例如中风。本发明的CRF受体拮抗剂具有以下结构式（I），包括立体异构体、前药和其药学上可接受的盐，其中R1、R2、R4、R5、R6、A、X和Y如本文所定义。还揭示了含有CRF受体拮抗剂与药学上可接受的载体组合的组合物，以及使用它们的方法。
• Tri-and tetraaza-acenaphthylen derivatives as crf receptor antagonists
  申请人：——

  公开号：US20040198726A1

  公开（公告）日：2004-10-07

  CRF receptor antagonists are disclosed which have utility in the treatment of a variety of disorders, including the treatment of disorders manifesting hypersecretion of CRF in a warm-blooded animals, such as stroke. The CRF receptor antagonists of this invention have the following structure of formula (I): including stereoisomers, prodrugs and pharmaceutically acceptable salts thereof, R1, R2, R4, R5, R6, A, X, and Y are as defined herein. Compositions containing a CRF receptor antagonist in combination with a pharmaceutically acceptable carrier are also disclosed, as well as methods for use of the same. 1

  本发明公开了CRF受体拮抗剂，这些拮抗剂可用于治疗多种疾病，包括治疗温血动物CRF分泌过多的疾病，如中风。本发明的 CRF 受体拮抗剂具有如下式（I）结构：包括其立体异构体、原药和药学上可接受的盐，R1、R2、R4、R5、R6、A、X 和 Y 如本文所定义。还公开了含有 CRF 受体拮抗剂与药学上可接受的载体结合的组合物，以及使用这些组合物的方法。 1
• TRI- AND TETRAAZA-ACENAPHTHYLEN DERIVATIVES AS CRF RECEPTOR ANTAGONISTS
  申请人：Neurocrine Biosciences, Inc.

  公开号：EP1392689A1

  公开（公告）日：2004-03-03
• US7446108B2
  申请人：——

  公开号：US7446108B2

  公开（公告）日：2008-11-04