达沙替尼杂质 | 1184919-23-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 达沙替尼杂质
• 英文名称: N-(2-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl]-2-methyl-4-pyrimidinyl]amino]-5-thiazolecarboxamide
• 英文别名: 2-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-N-(o-tolyl)thiazole-5-carboxamide；Deschloro Dasatinib；2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-methylphenyl)-1,3-thiazole-5-carboxamide
• CAS: 1184919-23-0
• 化学式: C₂₂H₂₇N₇O₂S
• 分子量: 453.568
• InChiKey: AMOFUFYOLNJZBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  32
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  135
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (E)-3-ethoxy-N-(2-methylphenyl)acrylamide 在 N-溴代丁二酰亚胺(NBS) 、 水 、 三乙胺 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 达沙替尼杂质
  参考文献：
  名称：

  2-氨基恶唑和 2-氨基噻唑达沙替尼衍生物作为慢性粒细胞白血病 K562 细胞的强效抑制剂

  摘要：

  达沙替尼是治疗慢性粒细胞白血病（CML）的重要药物。在本文中，我们描述了 2-氨基恶唑和 2-氨基噻唑达沙替尼衍生物的制备和抗 CML 活性。通过抑制人 CML K562 细胞的增殖来测量生物活性。2-氨基恶唑衍生物与2-氨基噻唑衍生物具有相似的活性。所有新合成的化合物都表现出比伊马替尼更有效的抗增殖活性。一些化合物（8b、8c、9b）显示出纳摩尔抑制活性，与达沙替尼相似。

  DOI：

  10.1002/ardp.201600010

文献信息

• INTRACELLULAR KINASE SIK3 ASSOCIATED WITH RESISTANCE AGAINST ANTI-TUMOUR IMMUNE RESPONSES, AND USES THEREOF
  申请人：iOmx Therapeutics AG

  公开号：EP3391907A1

  公开（公告）日：2018-10-24

  The invention is based on the surprising finding that SIK3 is associated with resistance against anti-tumour immune responses. In particular, the invention provides methods for treating proliferative diseases using inhibitors of SIK3, especially nucleic acid or small molecule inhibitors of SIK3. Also provided are methods of sensitising cells involved with a proliferative disorder against the cytotoxic effect of certain pro-inflammatory signalling pathways, and/or to kill such cells and/or methods for treating proliferative diseases, using a SIK3 inhibitor together with ligands or agonists of such signalling pathways. Other methods provided by the invention include those involving SIK3 inhibitors to enhance or overcome certain side effects associated with treatments that utilise such signalling pathways, as well as diagnostic, prognostic and monitoring methods and kits based on the detection of SIK3 in a sample obtained from a subject, and screening methods useful for identifying or characterising inhibitors of SIK3.

  本发明基于一个惊人的发现，即 SIK3 与抗肿瘤免疫反应的抵抗力有关。特别是，本发明提供了使用 SIK3 抑制剂，尤其是 SIK3 的核酸或小分子抑制剂治疗增殖性疾病的方法。本发明还提供了利用 SIK3 抑制剂和此类信号通路的配体或激动剂，使增殖性疾病相关细胞对某些促炎信号通路的细胞毒性作用敏感和/或杀死此类细胞和/或治疗增殖性疾病的方法。本发明提供的其他方法包括那些涉及 SIK3 抑制剂的方法，以增强或克服与利用此类信号通路的治疗相关的某些副作用，以及基于从受试者获得的样本中检测 SIK3 的诊断、预后和监测方法及试剂盒，以及用于识别或鉴定 SIK3 抑制剂的筛选方法。
• INTRACELLULAR KINASE ASSOCIATED WITH RESISTANCE AGAINST ANTI-TUMOUR IMMUNE RESPONSES, AND USES THEREOF
  申请人：iOmx Therapeutics AG

  公开号：US20210040486A1

  公开（公告）日：2021-02-11

  The invention is based on the surprising finding that SIK3 is associated with resistance against anti-tumour immune responses. In particular, the invention provides methods for treating proliferative diseases using inhibitors of SIK3, especially nucleic acid or small molecule inhibitors of SIK3. Also provided are methods of sensitising cells involved with a proliferative disorder against the cytotoxic effect of certain pro-inflammatory signalling pathways, and/or to kill such cells and/or methods for treating proliferative diseases, using a SIK3 inhibitor together with ligands or agonists of such signalling pathways. Other methods provided by the invention include those involving SIK3 inhibitors to enhance or overcome certain side effects associated with treatments that utilise such signalling pathways, as well as diagnostic, prognostic and monitoring methods and kits based on the detection of SIK3 in a sample obtained from a subject, and screening methods useful for identifying or characterising inhibitors of SIK3.
• 2-Aminoxazole and 2-Aminothiazole Dasatinib Derivatives as Potent Inhibitors of Chronic Myeloid Leukemia K562 Cells
  作者：Xing-Xing Chai、Zhi-Ping Cai、Mian-Tian Yang、Ying Zhou、Ying-Jun Fu、Yuan-Zhen Xiong

  DOI：10.1002/ardp.201600010

  日期：2016.7

  paper, we describe the preparation and anti‐CML activity of 2‐aminoxazole and 2‐aminothiazole dasatinib derivatives. Biological activity was measured by the inhibition of proliferation of human CML K562 cells. The 2‐aminoxazole derivatives had similar activities as the 2‐aminothiazole derivatives. All newly synthesized compounds demonstrated more potent antiproliferative activity than imatinib. A few

  达沙替尼是治疗慢性粒细胞白血病（CML）的重要药物。在本文中，我们描述了 2-氨基恶唑和 2-氨基噻唑达沙替尼衍生物的制备和抗 CML 活性。通过抑制人 CML K562 细胞的增殖来测量生物活性。2-氨基恶唑衍生物与2-氨基噻唑衍生物具有相似的活性。所有新合成的化合物都表现出比伊马替尼更有效的抗增殖活性。一些化合物（8b、8c、9b）显示出纳摩尔抑制活性，与达沙替尼相似。