N⁴-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-N¹,N¹-dimethyl-2-nitro-benzene-1,4-diamine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N⁴-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-N¹,N¹-dimethyl-2-nitro-benzene-1,4-diamine
• 英文别名: N~4~-[4-(2,4-Dimethyl-1,3-Thiazol-5-Yl)pyrimidin-2-Yl]-N~1~,N~1~-Dimethyl-2-Nitrobenzene-1,4-Diamine；4-N-[4-(2,4-dimethyl-1,3-thiazol-5-yl)pyrimidin-2-yl]-1-N,1-N-dimethyl-2-nitrobenzene-1,4-diamine
• 化学式: C₁₇H₁₈N₆O₂S
• 分子量: 370.435
• InChiKey: MYHBMTAGTIOCHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  128
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  N,N-二甲基-对苯二胺 在 sodium hydroxide 、 硝酸 、 乙酸酐 作用下， 以 乙醇 、 乙二醇甲醚 为溶剂， 反应 25.0h， 生成 N⁴-[4-(2,4-Dimethyl-thiazol-5-yl)-pyrimidin-2-yl]-N¹,N¹-dimethyl-2-nitro-benzene-1,4-diamine
  参考文献：
  名称：

  2-Anilino-4-(thiazol-5-yl)pyrimidine CDK Inhibitors:  Synthesis, SAR Analysis, X-ray Crystallography, and Biological Activity

  摘要：

  Following the identification through virtual screening of 4-(2,4-dimethyl-thiazol-5-yl)pyrimidin-2-ylamines as moderately potent inhibitors of cyclin-dependent kinase-2 (CDK2), a CDK inhibitor analogue program was initiated. The first aims were to optimize potency and to evaluate the cellular mode of action of lead candidate molecules. Here the synthetic chemistry, the structure-guided design approach, and the structure-activity relationships (SARs) that led to the discovery of 2-anilino-4-(thiazol-5-yl)pyrimidine ATP-antagonistic CDK2 inhibitors, many with very low nM K(i)s against CDK2, are reported. Furthermore, X-ray crystal structures of four representative analogues from our chemical series in complex with CDK2 are presented, and these structures are used to rationalize the observed biochemical SARs. Finally results are reported that show, using the most potent CDK2 inhibitor compound from the current series, that the observed antiproliferative and proapoptotic effects are consistent with cellular CDK2 and CDK9 inhibition.

  DOI：

  10.1021/jm0309957

文献信息

• [EN] N-(4-(4-METHYLTHIAZOL-5-YL) PYRIMIDIN-2-YL) -N-PHENYLAMINES AS ANTIPROLIFERATIVE COMPOUNDS<br/>[FR] N-(4-(4-METHYLTHIAZOL-5-YL) PYRIMIDINE-2-YL) -N-PHENYLAMINES COMME COMPOSES A ACTION ANTIPROLIFERANTE
  申请人：CYCLACEL LTD

  公开号：WO2003029248A1

  公开（公告）日：2003-04-10

  The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

  本发明涉及2-取代的4-杂环芳基嘧啶，它们的制备，包含它们的药物组合物以及它们作为细胞周期依赖性激酶（CDKs）的抑制剂的用途，因此可用于治疗增生性疾病，如癌症、白血病、牛皮癣等。
• N-(4-(4-methylthiazol-5-yl)pyrimidin-2-yl)-N-phenylamines as antiproliferative compounds
  申请人：——

  公开号：US20040259894A1

  公开（公告）日：2004-12-23

  The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukemia, psoriasis and the like.

  本发明涉及2-取代的4-杂环芳基嘧啶、它们的制备、含有它们的药物组合物以及它们作为细胞周期蛋白依赖性激酶（CDKs）的抑制剂的用途，因此可用于治疗增殖性疾病，如癌症、白血病、牛皮癣等。
• Anti-viral compounds
  申请人：Wang Shudong

  公开号：US20050288307A1

  公开（公告）日：2005-12-29

  The present invention relates to the use of 2-substituted 4-heteroaryl-pyrimidines and related compounds in the treatment of viral disorders.

  本发明涉及使用2-取代的4-杂环基嘧啶和相关化合物治疗病毒性疾病。
• N-(4-(4-methylthiazol-5-yl) pyrimidin-2-yl)-N-phenylamines as antiproliferative compounds
  申请人：Wang Shudong

  公开号：US20060199830A1

  公开（公告）日：2006-09-07

  The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

  本发明涉及2-取代的4-杂环芳基嘧啶，它们的制备，含有它们的药物组合物以及它们作为细胞周期蛋白依赖性激酶（CDKs）抑制剂的用途，因此可用于治疗增殖性疾病，如癌症、白血病、银屑病等。
• N-(4-(4-methylthiazol-5-yl) pyrimidin-2-yl)-N-phenylamines as anti-proliferative compounds
  申请人：Cyclacel Limited

  公开号：EP1760082A1

  公开（公告）日：2007-03-07

  The present invention relates to 2-substituted 4-heteroaryl-pyrimidines, their preparation, pharmaceutical compositions containing them and their use as inhibitors of cyclin-dependent kinases (CDKs) and hence their use in the treatment of proliferative disorders such as cancer, leukaemia, psoriasis and the like.

  本发明涉及 2-取代的 4-杂芳基嘧啶、其制备方法、含有它们的药物组合物以及它们作为细胞周期蛋白依赖性激酶（CDK）抑制剂的用途，因此它们可用于治疗增殖性疾病，如癌症、白血病、牛皮癣等。