4-甲氧基哒嗪 | 20733-11-3

• 物质功能分类: 医药中间体 - 哒嗪类化合物
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-甲氧基哒嗪
• 英文名称: 4-methoxypyridazine
• CAS: 20733-11-3
• 化学式: C₅H₆N₂O
• mdl: MFCD08236840
• 分子量: 110.115
• InChiKey: NSGNREBTEFKPIL-UHFFFAOYSA-N

物化性质

• 熔点：
  43-44℃
• 沸点：
  244℃
• 密度：
  1.102
• 闪点：
  89℃

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  8
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  35
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

制备方法与用途

4-甲氧基哒嗪是一种有用的科研化学品，广泛应用于有机合成及其他化学过程中。

反应信息

• 作为反应物：
  描述：

  4-甲氧基哒嗪 在 potassium hydrogencarbonate 、 hydroxylamine-O-sulfonic acid 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2E)-3-(dimethylamino)-1-(5-methoxypyrazolo[1,5-b]pyridazin-3-yl)prop-2-en-1-one
  参考文献：
  名称：

  N-Phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amines as Potent and Selective Inhibitors of Glycogen Synthase Kinase 3 with Good Cellular Efficacy

  摘要：

  Glycogen synthase kinase 3 regulates glycogen synthase, the rate-determining enzyme for glycogen synthesis. Liver and muscle glycogen synthesis is defective in type 2 diabetics, resulting in elevated plasma glucose levels. Inhibition of GSK-3 could potentially be an effective method to control plasma glucose levels in type 2 diabetics. Structure-activity studies on a N-phenyl-4-pyrazolo[1,5-b]pyridazin-3-ylpyrimidin-2-amine series have led to the identification of potent and selective compounds with good cellular efficacy. Molecular modeling studies have given insights into the mode of binding of these inhibitors. Since the initial leads were also potent inhibitors of CDK-2/CDK-4, an extensive SAR was performed at various positions of the pyrazolo[1,5-b]pyridazin core to afford potent GSK-3 inhibitors that were highly selective over CDK-2. In addition, these inhibitors also exhibited very good cell efficacy and functional response. A representative example was shown to have good oral exposure levels, extending their utility in an in vivo setting. These inhibitors provide a viable lead series in the discovery of new therapies for the treatment of type 2 diabetes.

  DOI：

  10.1021/jm040063i
• 作为产物：
  描述：

  3,6-二氯-4-甲氧基吡嗪 在 palladium on activated charcoal 、 乙醇 作用下， 生成 4-甲氧基哒嗪
  参考文献：
  名称：

  杂环研究中的化学研究。16. Mitteilung。哒嗪。3，4，6-三氯哒嗪取代

  摘要：

  3,4,6-三氯哒嗪被转化为许多新化合物，其结构由其化学和光谱性质确定。

  DOI：

  10.1002/hlca.19560390634

文献信息

• [EN] AMIDO-BENZYL SULFONE AND SULFONAMIDE DERIVATIVES<br/>[FR] DÉRIVÉS SULFONAMIDES ET SULFONES AMIDO-BENZYLIQUES
  申请人：GENENTECH INC

  公开号：WO2013127268A1

  公开（公告）日：2013-09-06

  Disclosed are certain amido-benzyl sulfone and sulfonamide compounds, pharmaceutical compositions comprising such compounds, land methods of treatment using such compounds.

  披露了某些氨基苯甲基砜和磺胺化合物，包括这些化合物的药物组合物，以及使用这些化合物的治疗方法。
• Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors
  作者：Scott H. Henderson、Fiona Sorrell、James Bennett、Oleg Fedorov、Marcus T. Hanley、Paulo H. Godoi、Roberta Ruela de Sousa、Sean Robinson、Alexander Ashall-Kelly、Iva Hopkins Navratilova、Daryl S. Walter、Jonathan M. Elkins、Simon E. Ward

  DOI：10.1021/acs.jmedchem.1c01115

  日期：2021.8.12

  pyrazolo[1,5-b]pyridazine inhibitors with excellent ligand efficiencies, good physicochemical properties, and a high degree of selectivity over the kinome. Compound 11 exhibited good permeability and cellular activity without P-glycoprotein liability, extending the utility of 11 in an in vivo setting. These pyrazolo[1,5-b]pyridazines are a viable lead series in the discovery of new therapies for the

  双特异性酪氨酸调节激酶​​ 1A (DYRK1A) 调节大脑发育过程中神经元祖细胞的增殖和分化。因此，DYRK1A 作为治疗神经退行性疾病（包括阿尔茨海默病（AD）和唐氏综合症）的靶标引起了人们的兴趣。最近，DYRK1A 的抑制已被研究为糖尿病的潜在治疗方法，而 DYRK1A 作为细胞周期介质的作用引起了人们对肿瘤适应症的兴趣。构效关系（SAR）分析与高分辨率X射线晶体学相结合，产生了一系列吡唑并[1,5- b ]哒嗪抑制剂，具有优异的配体效率、良好的理化性质以及对其他药物的高度选择性。激酶。化合物11表现出良好的渗透性和细胞活性，且无需 P-糖蛋白，从而扩展了11在体内环境中的效用。这些吡唑并[1,5- b ]哒嗪是发现治疗与 DYRK1A 功能相关疾病的新疗法的可行的先导系列。
• A Short and Efficient Synthesis of 3,4-Dialkoxypyrroles
  作者：Andreas Merz、Thomas Meyer

  DOI：10.1055/s-1999-3687

  日期：——

  3,4-Dialkoxypyrroles are obtained in four steps from commercially available 2,5-dimethoxy-2,5-dihydrofuran (1). The dihydrofuran 1 is first oxidized by KMnO4 to the diol 2 which is bisalkylated to 3a-d. Reaction of the in situ generated dialdehydes with a primary amine affords the N-substituted dialkoxypyrroles 4a-m. N-Benzyl-3,4-dialkoxypyrroles and N-allyl-dialkoxypyrroles are cleaved by sodium in liquid ammonia affording N-unsubstituted dialkoxypyrroles 5a-c in good overall yield.

  3,4-二烷氧基吡咯通过四个步骤从商业可得的2,5-二甲氧基-2,5-二氢呋喃（1）获得。首先，二氢呋喃1被KMnO4氧化成二醇2，然后对其进行双烷基化反应生成3a-d。通过与原位生成的双醛与一级胺反应，得到了N取代的双烷氧基吡咯4a-m。N-苄基-3,4-二烷氧基吡咯和N-烯丙基-双烷氧基吡咯在液氨中被钠裂解，获得了N-未取代的双烷氧基吡咯5a-c，整体产率良好。
• Studies on seven-membered heterocycles. XXXIII. Synthesis of fully unsaturated 1,2,5-triazepines by photochemical ring expansion of 4-azidopyridazines.
  作者：Hiroyuki SAWANISHI、Shuichi SAITO、Takashi TSUCHIYA

  DOI：10.1248/cpb.38.2992

  日期：——

  Photolysis of the 3-methoxy-4-azidopyridazines (11) in the presence of a base such as methoxide ion and diethylamine resulted in ring-expansion to produce the 1H-1, 2, 5-triazepines (12 and 27), which were too unstable to be isolated, but tautomerized to the stable 4H-isomers (13 and 28) on further treatment with sodium methoxide and were converted to the stable 1-acetyl-1H-1, 2, 5-triazepines (14 and 29) by acetylation with acetyl chloride. The products 12-14 and 27-29 are the first examples of fully unsaturated 1, 2, 5-triazepines and were characterized by means of spectral analyses and some chemical reactions.

  在甲氧基离子和二乙胺等碱存在下，3-甲氧基-4-叠氮哒嗪（11）发生光解，产生环状膨胀，生成 1H-1，2，5-三氮杂卓（12 和 27）、但在用甲醇钠进一步处理时，它们会同构化为稳定的 4H 异构体（13 和 28），并通过乙酰氯乙酰化转化为稳定的 1-乙酰基-1H-1，2，5-三氮杂卓（14 和 29）。产物 12-14 和 27-29 是完全不饱和的 1、2、5-三氮杂卓的第一个例子，并通过光谱分析和一些化学反应进行了表征。
• AMIDO SPIROCYCLIC AMIDE AND SULFONAMIDE DERIVATIVES
  申请人：GENENTECH, INC.

  公开号：US20160002266A1

  公开（公告）日：2016-01-07

  Provided are amido spirocyclic amide and sulfonamide compounds, pharmaceutical compositions comprising such compounds, and methods of treatment using such compounds.

  本发明提供了含有螺环酰胺和磺酰胺化合物的药物组合物，以及使用这些化合物的治疗方法。