ethyl 4-ethyloxoacetate-5-methylisoxazole-3-carboxylate | 502135-04-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: ethyl 4-ethyloxoacetate-5-methylisoxazole-3-carboxylate
• 英文别名: ethyl 4-(ethoxy(oxo)acetyl)-5-methylisoxazole-3-carboxylate；ethyl 4-[ethoxy(oxo)acetyl]-5-methylisoxazole-3-carboxylate；ethyl 4-(2-ethoxy-2-oxoacetyl)-5-methyl-1,2-oxazole-3-carboxylate
• CAS: 502135-04-8
• 化学式: C₁₁H₁₃NO₆
• 分子量: 255.227
• InChiKey: WLVRERDAOZUYKQ-UHFFFAOYSA-N

物化性质

• 沸点：
  405.1±45.0 °C(Predicted)
• 密度：
  1.250±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  95.7
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 4-ethyloxoacetate-5-methylisoxazole-3-carboxylate 在 palladium 10% on activated carbon 氢溴酸 、 氢气 、 potassium carbonate 、 肼 作用下， 以 DMF (N,N-dimethyl-formamide) 、 乙醇 、 水 为溶剂， 20.0~130.0 ℃ 、206.85 kPa 条件下， 反应 33.0h， 生成 4-methoxybenzyl 5-amino-1-ethyl-6-oxo-1,6-dihydropyridazine-3-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
• 作为产物：
  描述：

  氯代肟基乙酸乙酯 、 丙酮 在 sodium methylate 作用下， 以 乙醇 为溶剂， 反应 72.0h， 以90%的产率得到ethyl 4-ethyloxoacetate-5-methylisoxazole-3-carboxylate
  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

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。
• Pyridazin-3(2H)-one derivatives
  申请人：Laboratorios Almirall S.A.

  公开号：US07491722B2

  公开（公告）日：2009-02-17

  Pyridazin-3(2H)-one derivatives of formula (I) are found to inhibit PDE-4. R1, R2 and R4 are organic radicals, R3 is a cyclic group, and R5 is an ester or an aryl or heteroaryl group.

  公式（I）的吡啶并嗪-3（2H）-酮衍生物被发现能抑制PDE-4。其中，R1、R2和R4是有机基团，R3是一个环状基团，R5是一个酯基或芳基或杂环基团。
• [(3-Chlorophenyl)piperazinylpropyl]pyridazinones and Analogues as Potent Antinociceptive Agents
  作者：Maria Paola Giovannoni、Claudia Vergelli、Carla Ghelardini、Nicoletta Galeotti、Alessandro Bartolini、Vittorio Dal Piaz

  DOI：10.1021/jm021057u

  日期：2003.3.1

  A number of [(3-chlorophenyl)piperazinylpropyl]pyridazinones and the corresponding isoxazolo-pyridazinones, showing the arylpiperazinyl substructure present in very potent antinociceptive agents reported in the literature, were synthesized and tested for their analgesic activity. The investigated compounds showed antinociceptive properties in the mouse hot-plate test (thermal nociceptive stimulus) after systemic administration with an efficacy similar to that exerted by morphine. The increase of the pain threshold induced by the compounds labeled 5a, 7, 8, and 11 was prevented by reserpine, suggesting the involvement of the noradrenergic and/or serotoninergic system in their mechanism of action. Among them, 7 and 11 showed the highest analgesic potency and efficacy together with a good ratio (133 and 200, respectively) of the minimal nontoxic dose (MNTD) to the minimal analgesic dose (MAD). Furthermore, they were also active after icv administration and in the presence of a chemical, painful stimulus (abdominal constriction test).