ethyl 6-ethyl-3-methyl-7-oxo-6,7-dihydroisoxazolo[3,4-d]pyridazine-4-carboxylate | 720718-57-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: ethyl 6-ethyl-3-methyl-7-oxo-6,7-dihydroisoxazolo[3,4-d]pyridazine-4-carboxylate
• 英文别名: Ethyl 6-ethyl-3-methyl-7-oxo-[1,2]oxazolo[3,4-d]pyridazine-4-carboxylate
• CAS: 720718-57-0
• 化学式: C₁₁H₁₃N₃O₄
• 分子量: 251.242
• InChiKey: KRLTWDYNFMBHGX-UHFFFAOYSA-N

物化性质

• 沸点：
  410.1±47.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  85
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 6-ethyl-3-methyl-7-oxo-6,7-dihydroisoxazolo[3,4-d]pyridazine-4-carboxylate 在 lithium hydroxide 、 盐酸 、 水 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 5.0h， 以89%的产率得到6-乙基-3-甲基-7-氧代-6,7-二氢[1,2]恶唑并[3,4-d]哒嗪-4-羧酸
  参考文献：
  名称：

  [EN] NEW PYRIDAZIN-3(2H)-ONE DERIVATIVES
  [FR] NOUVEAUX DERIVES DE PYRIDAZIN-3(2H)-ONE

  摘要：

  式(I)的吡啶嗪-3(2H)-酮衍生物被发现能抑制PDE-4：其中R1、R2和R4为有机基团，R3为环状基团，R5为酯基或芳基或杂芳基。

  公开号：

  WO2004058729A1
• 作为产物：
  描述：

  乙酰丙酮酸乙酯 在 sodium ethanolate 、 potassium carbonate 、 肼 作用下， 以 DMF (N,N-dimethyl-formamide) 、 乙醇 为溶剂， 反应 20.0h， 生成 ethyl 6-ethyl-3-methyl-7-oxo-6,7-dihydroisoxazolo[3,4-d]pyridazine-4-carboxylate
  参考文献：
  名称：

  [EN] PYRIDAZIN-3(2H)-ONE DERIVATIVES AND THEIR USE AS PDE4 INHIBITORS
  [FR] DERIVES DE PYRIDAZIN-3(2H)-ONE ET LEUR UTILISATION EN TANT QU'INHIBITEURS DE LA PDE4

  摘要：

  该发明涉及公式（I）的新治疗上有用的吡啶嗪-3(2H)-酮衍生物，以及含有它们的药物组合物。这些化合物是磷酸二酯酶4（PDE4）的有效和选择性抑制剂，因此在治疗、预防或抑制病理状况、已知可通过PDE4抑制改善的疾病和疾病，如哮喘、慢性阻塞性肺病、类风湿性关节炎、特应性皮炎、牛皮癣或肠易激综合症方面是有用的。

  公开号：

  WO2005123692A1

文献信息

• New pyridazin-3(2h)-one derivatives
  申请人：Dal Piaz Vittorio

  公开号：US20060173008A1

  公开（公告）日：2006-08-03

  Pyridazin-3(2H)-one derivatives of formula (I) are found to inhibit PDE-4. R 1 , R 2 and R 4 are organic radicals, R 3 is a cyclic group, and R 5 is an ester or an aryl or heteroaryl group.

  公式（I）的吡啶并嗪-3（2H）-酮衍生物被发现可以抑制PDE-4。R1，R2和R4是有机基团，R3是一个环状基团，R5是酯基或芳基或杂环基团。
• Pyridazin-3(2H)-One Derivatives and Their Use as Pde4 Inhibitors
  申请人：Buil Albero Antonia Maria

  公开号：US20080280918A1

  公开（公告）日：2008-11-13

  The invention relates to new therapeutically useful pyridazin-3(2H)-one derivatives of Formula (I) and to pharmaceutical compositions containing them. These compounds are potent and selective inhibitors of phosphodiesterase 4 (PDE4) and are thus useful in the treatment, prevention or suppression of pathological conditions, diseases and disorders known to be susceptible of being improved by inhibition of PDE4 such as asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatilis, psoriasis or irritable bowel disease.

  本发明涉及公式（I）的新型治疗有用的吡啶并嗪-3（2H）-酮衍生物以及含有它们的药物组合物。这些化合物是磷酸二酯酶4（PDE4）的有效选择性抑制剂，因此在治疗、预防或抑制病理状态、疾病和疾病中具有用处，这些疾病已知通过抑制PDE4可被改善，例如哮喘、慢性阻塞性肺疾病、类风湿性关节炎、特应性皮炎、牛皮癣或肠易激综合征。
• NEW PYRIDAZIN-3(2H)-ONE DERIVATIVES
  申请人：Dal Piaz Vittorio

  公开号：US20090111819A1

  公开（公告）日：2009-04-30

  Pyridazin-3(2H)-one derivatives of formula (I) are found to inhibit PDE-4: wherein R 1 , R 2 and R 4 are organic radicals, R 3 is a cyclic group, and R 5 is an ester or an aryl or heteroaryl group.

  式(I)的吡啶并嗪-3(2H)-酮衍生物被发现能够抑制PDE-4，其中R1、R2和R4是有机基团，R3是环状基团，R5是酯基或芳基或杂环芳基基团。
• Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity
  作者：Pierfrancesco Biagini、Claudio Biancalani、Alessia Graziano、Nicoletta Cesari、Maria Paola Giovannoni、Agostino Cilibrizzi、Vittorio Dal Piaz、Claudia Vergelli、Letizia Crocetti、Maurizio Delcanale、Elisabetta Armani、Andrea Rizzi、Paola Puccini、Paola Maria Gallo、Daniele Spinabelli、Paola Caruso

  DOI：10.1016/j.bmc.2010.03.066

  日期：2010.5

  A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC50 in the nanomolar range. The ability to inhibit TNF-alpha release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform. (C) 2010 Elsevier Ltd. All rights reserved.
• PYRIDAZIN-3(2H)-ONE DERIVATIVES AND THEIR USE AS PDE4 INHIBITORS
  申请人：Almirall Prodesfarma, S.A.

  公开号：EP1758869A1

  公开（公告）日：2007-03-07