4-(苄基氨基)-2-((3-氯-4-羟基苯乙基)氨基)嘧啶-5-羧酰胺 | 919486-40-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 4-(苄基氨基)-2-((3-氯-4-羟基苯乙基)氨基)嘧啶-5-羧酰胺
• 英文名称: AS 1517499
• 英文别名: 4-(Benzylamino)-2-((3-chloro-4-hydroxyphenethyl)amino)pyrimidine-5-carboxamide；4-(benzylamino)-2-[2-(3-chloro-4-hydroxyphenyl)ethylamino]pyrimidine-5-carboxamide
• CAS: 919486-40-1
• 化学式: C₂₀H₂₀ClN₅O₂
• 分子量: 397.864
• InChiKey: OZRMEKAUZBKTTC-UHFFFAOYSA-N

物化性质

• 溶解度：
  DMF：25mg/mL； DMF:PBS (pH 7.2) (1:6)：0.14mg/mL；二甲基亚砜：15mg/mL；乙醇：5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  113
• 氢给体数：
  4
• 氢受体数：
  6

安全信息

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

制备方法与用途

生物活性

AS1517499是一种新型有效的STAT6抑制剂，IC50为21 nM。

靶点

Target	Value
STAT6 (Cell-free assay)	21 nM

体外研究

AS1517499能有效抑制IL-4诱导的小鼠脾脏T细胞向Tb分化，但不对IL-12诱导的Tb分化产生影响。此外，该化合物还能阻止IL-4激活下由STAT6介导的原代PCa细胞形成克隆潜力的增加；在浓度为300 nM时，AS1517499亦能降低原代基底PCa细胞的形成克隆潜能。

体内研究

在小鼠体内的实验中，通过处理AS1517499，可以观察到其能够抑制气管平滑肌中RhoA的上调，从而减缓由抗原诱导的气管平滑肌高反应性现象。这可能是由于AS1517499降低了小鼠气管内IL-13的产生所致。此外，该化合物还能通过抑制PPARγ来减少bleomycin诱导的肺纤维化过程中凋亡细胞灌注的影响。

反应信息

• 作为产物：
  描述：

  4-氯-2-甲硫基嘧啶-5-羧酸乙酯 在 N-甲基吡咯烷酮 、 ammonium hydroxide 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 二异丙胺 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 30.0h， 生成 4-(苄基氨基)-2-((3-氯-4-羟基苯乙基)氨基)嘧啶-5-羧酰胺
  参考文献：
  名称：

  Synthesis and evaluation of 2-{[2-(4-hydroxyphenyl)-ethyl]amino}pyrimidine-5-carboxamide derivatives as novel STAT6 inhibitors

  摘要：

  The STAT6 (signal transducers and activators of transcription 6) protein is activated by interleukin (IL)-4 and IL-13, and plays an important role in T-helper cell 2 (Th2) differentiation. STAT6 might therefore be an excellent therapeutic target for various allergic conditions, including asthma and atopic diseases. We synthesized a series of 2-{[2-(4-hydroxyphenyl)ethyl]amino}pyrimidine-5-carboxamide derivatives and evaluated their STAT6 inhibitory activities. Among these compounds, 4-(benzylamino)-2-{[2-(3-chloro-4-hydroxyphenyl)ethyl]amino}pyrimidine-5-carboxamide (2t, AS1517499) showed potent STAT6 inhibition with an IC50 value of 21 nM, and also inhibited IL-4-induced Th2 differentiation of mouse spleen T cells with an IC50 value of 2.3 nM and without influencing T-helper cell 1 (Th1) differentiation induced by IL-12. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.015

文献信息

• Diaminopyrimidinecarboxa mide derivative
  申请人：Nagashima Shinya

  公开号：US20050272753A1

  公开（公告）日：2005-12-08

  A compound which may be used for the prevention or treatment of respiratory diseases in which STAT 6 is concerned, particularly asthma, chronic obstructive pulmonary disease and the like is provided. A pyrimidine derivative or a salt thereof, which has an arylamino or arylethylamino group which may be substituted with a specified substituent, at the 2-position, amino group substituted with benzyl group or the like, at the 4-position, and carbamoyl group which may be substituted, at the 5-position, is provided.

  提供了一种可用于预防或治疗呼吸道疾病，特别是哮喘、慢性阻塞性肺病等与STAT 6有关的化合物。该化合物是一种嘧啶衍生物或其盐，其在2位具有可以被指定取代基取代的芳基氨基或芳基乙基氨基，4位具有被苄基基团或类似基团取代的氨基，5位具有可以被取代的氨基甲酰基。
• Diaminopyrimidinecarboxamide Derivative
  申请人：Nagashima Shinya

  公开号：US20090281072A1

  公开（公告）日：2009-11-12

  A compound which may be used for the prevention or treatment of respiratory diseases in which STAT 6 is concerned, particularly asthma, chronic obstructive pulmonary disease and the like is provided. A pyrimidine derivative or a salt thereof, which has an arylamino or arylethylamino group which may be substituted with a specified substituent, at the 2-position, amino group substituted with benzyl group or the like, at the 4-position, and carbamoyl group which may be substituted, at the 5-position, is provided.

  提供了一种可用于预防或治疗呼吸系统疾病，特别是哮喘、慢性阻塞性肺疾病等与STAT 6有关的化合物。该化合物为嘧啶衍生物或其盐，其在2位具有可被取代的芳基氨基或芳基乙基氨基基团，4位具有氨基取代的苯甲基基团或类似基团，5位具有可被取代的氨基甲酰基团。
• DIAMINOPYRIMIDINECARBOXAMIDE DERIVATIVE
  申请人：Nagashima Shinya

  公开号：US20110294749A1

  公开（公告）日：2011-12-01

  A compound which may be used for the prevention or treatment of respiratory diseases in which STAT 6 is concerned, particularly asthma, chronic obstructive pulmonary disease and the like is provided. A pyrimidine derivative or a salt thereof, which has an arylamino or arylethylamino group which may be substituted with a specified substituent, at the 2-position, amino group substituted with benzyl group or the like, at the 4-position, and carbamoyl group which may be substituted, at the 5-position, is provided.

  提供了一种可用于预防或治疗涉及STAT 6的呼吸系统疾病，特别是哮喘、慢性阻塞性肺疾病等的化合物。该化合物为嘧啶衍生物或其盐，其在2位具有可以被指定取代基取代的芳基氨基或芳基乙基氨基基团，在4位具有可以被苄基或类似物取代的氨基基团，并在5位具有可以被取代的氨基甲酰基团。
• Diaminopyrimidinecarboxamide derivative
  申请人：Astellas Pharma Inc.

  公开号：US08012959B2

  公开（公告）日：2011-09-06

  A compound which may be used for the prevention or treatment of respiratory diseases in which STAT 6 is concerned, particularly asthma, chronic obstructive pulmonary disease and the like is provided. A pyrimidine derivative or a salt thereof, which has an arylamino or arylethylamino group which may be substituted with a specified substituent, at the 2-position, amino group substituted with benzyl group or the like, at the 4-position, and carbamoyl group which may be substituted, at the 5-position, is provided.

  提供一种可用于预防或治疗与STAT 6有关的呼吸道疾病，特别是哮喘、慢性阻塞性肺病等的化合物。提供一种嘧啶衍生物或其盐，其具有在2位上可以被取代的芳基氨基或芳基乙基氨基基团，4位上取代苯甲基或类似物的氨基基团，以及在5位上可以被取代的碳酰基团。
• DIAMINOPYRIMIDINECARBOXA MIDE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP1518855B1

  公开（公告）日：2011-10-26