4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one | 380227-28-1

• 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-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydro-2H-phthalazin-1-one
• CAS: 380227-28-1
• 化学式: C₁₆H₂₀N₂O₃
• 分子量: 288.346
• InChiKey: QKTDYBBFKUXEOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 20.0~120.0 ℃ 、2.76 MPa 条件下， 反应 7.67h， 生成 N-(5-(2-((2-(4-(3,4-dimethoxyphenyl)-1-oxo-4a,5,6,7,8,8a-hexahydrophthalazin-2(1H)-yl)hexyl)amino)-1-hydroxyethyl)-2-hydroxyphenyl)formamide
  参考文献：
  名称：

  Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD

  摘要：

  We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both beta 2-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC50 = 0.278 mu M, which was more potent than phthalazinone, IC50 = 0.520 mu M) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC(50) = 9.3). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.013
• 作为产物：
  描述：

  六氢苯酐 在 aluminum (III) chloride 、 一水合肼 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 27.0h， 生成 4-(3,4-dimethoxyphenyl)-4a,5,8,8a-tetrahydro-2H-phthalazin-1-one
  参考文献：
  名称：

  Dual β2-adrenoceptor agonists-PDE4 inhibitors for the treatment of asthma and COPD

  摘要：

  We designed and synthesized a novel class of dual pharmacology bronchodilators targeting both beta 2-adrenoceptor and PDE4 by applying a multivalent approach. The most potent dual pharmacology molecule, compound 29, possessed good inhibitory activity on PDE4B2 (IC50 = 0.278 mu M, which was more potent than phthalazinone, IC50 = 0.520 mu M) and possessed excellent relaxant effects on tracheal rings precontracted by histamine (pEC(50) = 9.3). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.013

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。
• PHTHALAZINONE DERIVATIVE AND PHARMACEUTICAL COMPRISING THE SAME
  申请人：Nippon Shinyaku Co., Ltd.

  公开号：EP1873147A1

  公开（公告）日：2008-01-02

  [Problem] The present invention is to provide a novel compound having an excellent PDE4 inhibitory activity and TNF-α production-suppressing activity, and also to provide a preventive and therapeutical agent for atopic dermatitis or the like. [Means for Solution] 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 following partial structure bridging the 6-position and the 7-position represents a single bond or a double bond: R1 and R2 are the same or different and each represents alkyl or the like, Y represents phenylene or the like, Z represents alkylene or the like, R3 represents a mono- to tri-cyclic saturated or unsaturated cyclic amino group or the like, R31 and R32 represent alkyl or the like.

  [问题]本发明旨在提供一种新型化合物，该化合物具有优异的PDE4抑制活性和TNF-α生成抑制活性，同时提供一种特应性皮炎或类似疾病的预防和治疗剂。 [解决方法]本发明包括以下通式结构式[1]的新型酞嗪酮衍生物或其药学上可接受的盐，以及以其为活性成分的药物组合物。 在结构式[1]中 以下连接 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，各自代表烷基或类似物，Y代表亚苯基或类似物，Z代表亚烷基或类似物，R3代表单环至三环饱和或不饱和环状氨基或类似物，R31和R32代表烷基或类似物。
• PHTHALAZINONES
  申请人：ALTANA Pharma AG

  公开号：EP0971901B1

  公开（公告）日：2003-02-26
• US6103718A
  申请人：——

  公开号：US6103718A

  公开（公告）日：2000-08-15