6-methoxyimidazo[1,2-b]pyridazin-3-carboxylic acid | 1339175-86-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 6-methoxyimidazo[1,2-b]pyridazin-3-carboxylic acid
• 英文别名: 6-methoxyimidazo[1,2-b]pyridazine-3-carboxylic acid；6-Methoxyimidazo[1,2-b]pyridazine-3-carboxylic acid
• CAS: 1339175-86-8
• 化学式: C₈H₇N₃O₃
• 分子量: 193.162
• InChiKey: DUMKIBBUGQQMHR-UHFFFAOYSA-N

物化性质

• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  76.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-(3-amino-2,2,4,4-tetramethylcyclobutoxy)-2-methylnicotinonitrile hydrochloride 、 6-methoxyimidazo[1,2-b]pyridazin-3-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 N-{trans-3-[(5-cyano-6-methylpyridin-2-yl)oxy]-2,2,4,4-tetramethylcyclobutyl}-6-methoxyimidazo[1,2-b]pyridazine-3-carboxamide
  参考文献：
  名称：

  Systematic Structure Modifications of Imidazo[1,2-a]pyrimidine to Reduce Metabolism Mediated by Aldehyde Oxidase (AO)

  摘要：

  N-{trans-3-[(5-Cyano-6-methylpyridin-2-yl)oxy] 2,2,4,4-tetramethylcyclobutyl}imidazo [1,2-a]pyrimidine-3-carboxamide (1) was recently identified as a full antagonist of the androgen receptor, demonstrating excellent in vivo tumor growth inhibition in castration-resistant prostate cancer (CRPC). However, the imidazo[1,2-a]pyrimidine moiety is rapidly metabolized by aldehyde oxidase (AO). The present paper describes a number of medicinal chemistry strategies taken to avoid the AO-mediated oxidation of this particular system. Guided by an AO protein structure-based model, our investigation revealed the most probable site of AO oxidation and the observation that altering the heterocycle or blocking the reactive site are two of the more effective strategies for reducing AO metabolism. These strategies may be useful for other drug discovery programs.

  DOI：

  10.1021/jm2010942
• 作为产物：
  描述：

  (E)-N'-(6-chloropyridazin-3-yl)-N,N-dimethylformimidamide 以 四氢呋喃 、 水 、 乙腈 为溶剂， 反应 11.0h， 生成 6-methoxyimidazo[1,2-b]pyridazin-3-carboxylic acid
  参考文献：
  名称：

  咪唑并哒嗪类IRAK4抑制剂及其制备方法和应用

  摘要：

  本发明属于药物领域，特别涉及一种咪唑并哒嗪类化合物或其药学上可接受的盐及其制备方法和其药用组合物在治疗肿瘤，炎症，免疫等疾病中的应用。本发明涉及的咪唑并哒嗪类化合物是一种新型蛋白激酶IRAK4抑制剂，能选择性抑制IRAK4及其下游信号通路。本发明所述化合物具有结构式I。

  公开号：

  CN107652293A

文献信息

• [EN] AMIDO-SUBSTITUTED CYCLOHEXANE DERIVATIVES<br/>[FR] DÉRIVÉS DE CYCLOHEXANE À SUBSTITUTION AMIDO
  申请人：BAYER PHARMA AG

  公开号：WO2016177658A1

  公开（公告）日：2016-11-10

  The present invention relates to amido-substituted cyclohexane compounds of general formula (I), in which A, R4, R6, R7, R8, R9, R10 and R11 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredient.

  本发明涉及一般式(I)的酰胺取代环己烷化合物，其中A、R4、R6、R7、R8、R9、R10和R11如本文所定义，涉及制备所述化合物的方法，涉及用于制备所述化合物的中间化合物，涉及包含所述化合物的药物组合物和药物组合物，以及用于制造用于治疗或预防疾病的药物组合物的所述化合物的用途，特别是肿瘤，作为唯一药剂或与其他活性成分结合使用。
• AMIDO-SUBSTITUTED CYCLOHEXANE DERIVATIVES
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP3292107A1

  公开（公告）日：2018-03-14
• 咪唑并哒嗪类IRAK4抑制剂及其制备方法和应用
  申请人：中国药科大学

  公开号：CN107652293A

  公开（公告）日：2018-02-02

  本发明属于药物领域，特别涉及一种咪唑并哒嗪类化合物或其药学上可接受的盐及其制备方法和其药用组合物在治疗肿瘤，炎症，免疫等疾病中的应用。本发明涉及的咪唑并哒嗪类化合物是一种新型蛋白激酶IRAK4抑制剂，能选择性抑制IRAK4及其下游信号通路。本发明所述化合物具有结构式I。
• Systematic Structure Modifications of Imidazo[1,2-<i>a</i>]pyrimidine to Reduce Metabolism Mediated by Aldehyde Oxidase (AO)
  作者：Angelica Linton、Ping Kang、Martha Ornelas、Susan Kephart、Qiyue Hu、Mason Pairish、Ying Jiang、Chuangxing Guo

  DOI：10.1021/jm2010942

  日期：2011.11.10

  N-trans-3-[(5-Cyano-6-methylpyridin-2-yl)oxy] 2,2,4,4-tetramethylcyclobutyl}imidazo [1,2-a]pyrimidine-3-carboxamide (1) was recently identified as a full antagonist of the androgen receptor, demonstrating excellent in vivo tumor growth inhibition in castration-resistant prostate cancer (CRPC). However, the imidazo[1,2-a]pyrimidine moiety is rapidly metabolized by aldehyde oxidase (AO). The present paper describes a number of medicinal chemistry strategies taken to avoid the AO-mediated oxidation of this particular system. Guided by an AO protein structure-based model, our investigation revealed the most probable site of AO oxidation and the observation that altering the heterocycle or blocking the reactive site are two of the more effective strategies for reducing AO metabolism. These strategies may be useful for other drug discovery programs.