4-[[[4-[(2.6-二甲基-3-吡啶基)氧基]-2-吡啶基]氨基]苯磺酰胺 | 1117684-36-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 4-[[[4-[(2.6-二甲基-3-吡啶基)氧基]-2-吡啶基]氨基]苯磺酰胺
• 英文名称: 4-({4-[(2,6-dimethyl-3-pyridinyl)oxy]-2-pyridinyl}amino)benzenesulfonamide
• 英文别名: 4-({4-[(2,6-dimethylpyridin-3-yl)oxy]pyridin-2-yl}amino)benzenesulfonamide；AZ12799734；4-({4-[(2,6-dimethylpyridin-3-yl)oxy]pyridin-2-yl}amino)-benzenesulfonamide；4-[[4-(2,6-dimethylpyridin-3-yl)oxypyridin-2-yl]amino]benzenesulfonamide
• CAS: 1117684-36-2
• 化学式: C₁₈H₁₈N₄O₃S
• 分子量: 370.432
• InChiKey: UEOZXMAOIHDDQE-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

制备方法与用途

AZ-12799734（AZ12799734）是一种泛BMP/TGFβ抑制剂，能够有效抑制配体激活下的SMAD3/4转录，其IC50为47 nM。该化合物还能抑制ALK1、BMPR1A和BMPR1B对SMAD1的受体介导磷酸化以及ALK4对SMAD2的磷酸化作用，并且能够抑制TGFβ诱导的HaCaT细胞迁移。

反应信息

• 作为产物：
  描述：

  3-((2-chloropyridin-4-yl)oxy)-2,6-dimethylpyridine 、 磺胺 在 palladium diacetate caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 异丁酰胺 为溶剂， 反应 0.17h， 以54%的产率得到4-[[[4-[(2.6-二甲基-3-吡啶基)氧基]-2-吡啶基]氨基]苯磺酰胺
  参考文献：
  名称：

  CHEMICAL COMPOUNDS-821

  摘要：

  该发明涉及化学式(I)的化合物，或其药学上可接受的盐，具有ALK5（TGFβR1）抑制活性，因此在抗癌活性方面有用，从而在治疗人体或动物体的方法中有用。该发明还涉及制造上述化学化合物的方法，含有它们的药物组合物，以及它们在制造用于在温血动物（如人）中产生抗癌效果的药物中的使用。

  公开号：

  US20090048269A1

文献信息

• ANTIBODY-ALK5 INHIBITOR CONJUGATES AND THEIR USES
  申请人：Synthis, LLC

  公开号：US20200147234A1

  公开（公告）日：2020-05-14

  The present disclosure relates to antibody-drug conjugates comprising ALK5 inhibitors and their uses.

  本公开涉及包含ALK5抑制剂的抗体药物偶联物及其用途。
• Compounds and methods for selectively targeting tumor-associated mucins
  申请人：B & G Partners, LLC

  公开号：EP2409708A1

  公开（公告）日：2012-01-25

  The present invention relates to pharmaceutical compositions containing tumor-selective targeted inhibitor glycoconjugates. These bioconjugates are ALK5 inhibitors covalently bound to biocompatible carrier molecules which selectively target and specifically bind to Muc4 that is overexpressed on a variety of tumor cell types. The ALK5 inhibitors are conjugated to tumor targetable glycans through a covalent linker. Preferably the acid-labile linker is designed to be stable in plasma and releases pharmacologically active inhibitors through acid-catalyzed hydrolysis in the acidic environment of the target tumor where the inhibitor activity is restored. Because the glycoconjugates are stable at physiological pH and in plasma, they advantageously reduce undesirable systemic ALK5 inhibitor activity; however, the preferable glycoconjugates are acid-labile conjugates that can be hydrolyzed upon reaching the more acid environment of the tumor.

  本发明涉及含有肿瘤选择性靶向抑制剂糖共轭物的药物组合物。这些生物共轭物是与生物相容性载体分子共价结合的 ALK5 抑制剂，可选择性地靶向和特异性地结合多种肿瘤细胞类型上过度表达的 Muc4。ALK5 抑制剂通过共价连接体与肿瘤靶向性聚糖共轭。最好设计成在血浆中稳定，并在靶向肿瘤的酸性环境中通过酸催化水解释放出具有药理活性的抑制剂，从而恢复抑制剂的活性。由于糖轭合物在生理pH值和血浆中稳定，因此它们能减少不希望出现的全身性ALK5抑制剂活性；然而，优选的糖轭合物是耐酸轭合物，在到达肿瘤的酸性环境时可被水解。
• CELL CULTURE MEDIUM, CULTURE METHOD, AND ORGANOID
  申请人：Keio University

  公开号：EP3418376A1

  公开（公告）日：2018-12-26

  The present invention provides a cell culture medium with which serum-free long-term culture of an epithelial stem cell, an epithelial cancer cell, or a tissue containing at least one thereof can be achieved. The cell culture medium of the present invention includes: a Wnt agonist composed of a complex of Wnt protein and afamin, which is a substance capable of stabilizing the Wnt protein, and R-spondin; and at least one selected from the group consisting of a mitogenic growth factor, a bone morphogenetic protein (BMP) inhibitor, a transforming growth factor-β (TGF-β) inhibitor, and a p38 inhibitor.

  本发明提供了一种细胞培养基，用它可以实现上皮干细胞、上皮癌细胞或含有其中至少一种细胞的组织的无血清长期培养。本发明的细胞培养基包括：Wnt 激动剂，由 Wnt 蛋白和阿法明（一种能够稳定 Wnt 蛋白的物质）的复合物以及 R-spondin 组成；以及至少一种选自有丝分裂生长因子、骨形态发生蛋白（BMP）抑制剂、转化生长因子-β（TGF-β）抑制剂和 p38 抑制剂组的物质。
• CELL CULTURE MEDIUM FOR CULTURING ORGANOID, CULTURE METHOD, AND ORGANOID
  申请人：Keio University

  公开号：EP3460042A1

  公开（公告）日：2019-03-27

  A cell culture medium for culturing organoid containing at least two types of components selected from the group consisting of insulin-like growth factor 1 (IGF1), fibroblast growth factor 2 (FGF2) and epiregulin (EREG), and at least one type of component among the following components i) to iii): i) Wnt agonist, ii) bone morphogenetic protein (BMP) inhibitor, and iii) transforming growth factor-β (TGF-β) inhibitor.

  一种用于培养类器官的细胞培养基，含有至少两种从胰岛素样生长因子 1 (IGF1)、成纤维细胞生长因子 2 (FGF2)和表皮生长因子 (EREG) 组成的组中选出的成分，以及以下成分 i) 至 iii) 中的至少一种成分：i) Wnt 激动剂；ii) 骨形态发生蛋白 (BMP) 抑制剂；iii) 转化生长因子-β (TGF-β) 抑制剂。
• 2D ORGANOID FOR INFECTION AND CULTURE OF HUMAN DIARRHEA VIRUS, AND USE OF SAID 2D ORGANOID
  申请人：Keio University

  公开号：EP3505620A1

  公开（公告）日：2019-07-03

  A 2D organoid for infection and growth culture of human diarrhea virus is obtained by: a step 1 in which a human intestinal epithelial stem cell, a human intestinal epithelial cell, or a tissue containing at least any of these cells is three-dimensionally cultured on an extracellular matrix to obtain a 3D organoid; and a step 2 in which the 3D organoid obtained in the step 1 is dispersed to prepare a single cell, and the single cell is monolayer-cultured on an extracellular matrix to obtain a 2D organoid in which epithelial cells containing differentiated trophoblastic cells and goblet cells and configuring human intestinal lumen have a monolayer structure.

  一种用于人类腹泻病毒感染和生长培养的二维类器官是通过以下方法获得的：步骤1：将人肠上皮干细胞、人肠上皮细胞或至少含有上述任一细胞的组织在细胞外基质上进行三维培养，得到三维类器官；步骤 2：将步骤 1 中获得的三维类器官分散制备单细胞，并将单细胞在细胞外基质上进行单层培养，以获得二维类器官，其中的上皮细胞包含已分化的滋养层细胞和鹅口疮细胞，并配置人体肠腔的单层结构。