4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one | 357980-82-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• 英文别名: 4-(3,4-Dimethoxy-phenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
• CAS: 357980-82-6
• 化学式: C₁₆H₁₈N₂O₃
• 分子量: 286.331
• InChiKey: MRBFFQVXMIGKST-UHFFFAOYSA-N

物化性质

• 密度：
  1.28±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  59.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 14.67h， 生成 N-(5-(2-(benzyl(1-(4-(4-(4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,6,7,8,8a-hexahydrophthalazin-2(1H)-yl)butoxy)phenyl)propan-2-yl)amino)-1-hydroxyethyl)-2-(benzyloxy)phenyl)formamide
  参考文献：
  名称：

  Design, synthesis and evaluation of dual pharmacology β2-adrenoceptor agonists and PDE4 inhibitors

  摘要：

  A novel series of formoterol-phthalazinone hybrids were synthesised and evaluated as dual pharmacology beta(2)-adrenoceptor agonists and PDE4 inhibitors. Most of the hybrids displayed high beta(2)-adrenoceptor agonist and moderate PDE4 inhibitory activities. The most potent compound, (R, R)-11c, exhibited agonist (EC50 = 1.05 nM, pEC(50) = 9.0) and potent PDE4B2 inhibitory activities (IC50 = 0.092 mu M). (C) 2013 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2013.11.028
• 作为产物：
  描述：

  cis-1,2,3,6-tetrahydrophthalic anhydride 在 一水合肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
  参考文献：
  名称：

  Stereoselective inhibition of serotonin re-uptake and phosphodiesterase by dual inhibitors as potential agents for depression

  摘要：

  Multi-target compounds where more than one functional activity is incorporated into the same molecule may have advantages in treating disease states. Selective serotonin re-uptake inhibitors (SSRIs)(a) (i.e., (R)- and (S)-norfluoxetine) were chemically linked to a PDE4 inhibitor via a five carbon bridge. The new dual PDE4 inhibitor/SSRIs (i.e., (R)-8 and (S)-8) showed moderately potent but highly selective serotonin re-uptake inhibition (IC50 values of 173 and 42 nM, respectively) in vitro. The dual PDE4 inhibitor/SSRIs (R)-8 and (S)-8 also inhibited PDE4D2 (i.e., K-i values of 106 and 253 nM, respectively). Due to the synergistic functional activity, PDE4 inhibitor/SSRIs may be effective in treating diseases such as depression. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2008.10.065

文献信息

• Compounds effective as beta-2 adrenoreceptor agonists as well pde4-inhibitors
  申请人：——

  公开号：US20030195215A1

  公开（公告）日：2003-10-16

  The compounds of formula I in which Ar 1 , A, R6, R7, R8 and Ar 2 have the meanings as given in the description are novel effective bronchial therapeutics. 1

  式I的化合物中，其中Ar1、A、R6、R7、R8和Ar2的含义如描述所示，是一种新型有效的支气管治疗剂。
• PHTHALAZINONE DERIVATIVES AND PHARMACEUTICAL COMPOSITIONS COMPRISING THE SAME
  申请人：Kagayama Kohei

  公开号：US20090042879A1

  公开（公告）日：2009-02-12

  The present invention provides a novel compound having an excellent PDE4 inhibitory activity and TNF-α production-suppressing activity, and also provides a preventive and therapeutic agent for atopic dermatitis or the like. The present invention includes a novel phthalazinone derivative of the following general structural formula [1] or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising it as an active ingredient. In the structural formula [1], the partial structure bridging the 6-position and the 7-position represents a single bond or a double bond; R 1 and R 2 are the same or different and each represents alkyl or the like; Y represents phenylene or the like; Z represents alkylene or the like; and R 3 represents a mono- to tri-cyclic saturated or unsaturated cyclic amino group or the like optionally substituted with R 31 and R 32 , wherein R 31 and R 32 represent alkyl or the like.

  本发明提供了一种具有优异的PDE4抑制活性和TNF-α产生抑制活性的新型化合物，同时还提供了预防和治疗特应性皮炎或类似疾病的药物。本发明包括以下一般结构式[1]的新型邻苯二酮衍生物或其药学上可接受的盐，以及包含其作为活性成分的制药组合物。在结构式[1]中，连接6位和7位的部分结构代表单键或双键；R1和R2相同或不同，分别代表烷基或类似物；Y代表苯撑基或类似物；Z代表烷基或类似物；R3代表单环至三环饱和或不饱和环状氨基或类似物，可选地被R31和R32取代，其中R31和R32代表烷基或类似物。
• Modulators of Central Nervous System Neurotransmitters
  申请人：Cashman John

  公开号：US20080261967A1

  公开（公告）日：2008-10-23

  Disclosed are agents having pharmacological activity against cellular receptors and intracellular signaling, particularly receptors and signaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.

  本发明涉及具有药理活性的药物，特别是针对细胞受体和细胞内信号传导的药物，尤其是中枢神经系统（CNS）神经递质的受体和信号通路。本发明还涉及使用这些药物的相关方法和组合物，用于治疗或预防疾病或障碍。
• Modulators of central nervous system neurotransmitters
  申请人：Human BioMolecular Research Institute

  公开号：US08168635B2

  公开（公告）日：2012-05-01

  Disclosed are agents having pharmacological activity against cellular receptors and intracellular signaling, particularly receptors and signaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.

  本发明涉及一种具有药理活性的制剂，可用于靶向细胞受体和细胞内信号通路，特别是中枢神经系统（CNS）神经递质的受体和信号通路。同时，本发明还涉及使用该制剂进行疾病或障碍的治疗或预防的相关方法和组合物。
• MODULATORS OF CENTRAL NERVOUS SYSTEM NEUROTRANSMITTERS
  申请人：CASHMAN John

  公开号：US20130123253A1

  公开（公告）日：2013-05-16

  Disclosed are agents having pharmacological activity against cellular receptors and intracellular signaling, particularly receptors and signaling pathways of central nervous system (CNS) neurotransmitters. Also disclosed are related methods and compositions for the treatment or prevention of diseases or disorders using the agents.

  本发明涉及一种对细胞受体和细胞内信号传导具有药理活性的药剂，特别是针对中枢神经系统（CNS）神经递质的受体和信号通路。本发明还涉及使用这些药剂的相关方法和组合物，用于治疗或预防疾病或障碍。