N-(5-(2-(cyclohexyloxy)-6-methylpyrimidin-4-yl)thiazol-2-yl)-5-((4-methylpiperazin-1-yl)methyl)pyrazin-2-amine | 874473-15-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(5-(2-(cyclohexyloxy)-6-methylpyrimidin-4-yl)thiazol-2-yl)-5-((4-methylpiperazin-1-yl)methyl)pyrazin-2-amine
• 英文别名: 5-(2-cyclohexyloxy-6-methylpyrimidin-4-yl)-N-[5-[(4-methylpiperazin-1-yl)methyl]pyrazin-2-yl]-1,3-thiazol-2-amine
• CAS: 874473-15-1
• 化学式: C₂₄H₃₂N₈OS
• 分子量: 480.637
• InChiKey: DLIDUXYWQPLFEM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  (5-溴乙基吡嗪-2-基)氨基甲酸叔丁酯 在 咪唑 、 盐酸 、 sodium hydroxide 、 18-冠醚-6 、 四丁基氟化铵 、 sodium hydride 、 potassium carbonate 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 70.5h， 生成 N-(5-(2-(cyclohexyloxy)-6-methylpyrimidin-4-yl)thiazol-2-yl)-5-((4-methylpiperazin-1-yl)methyl)pyrazin-2-amine
  参考文献：
  名称：

  Identification of potent 5-pyrimidinyl-2-aminothiazole CDK4, 6 inhibitors with significant selectivity over CDK1, 2, 5, 7, and 9

  摘要：

  5-Pyrimidinyl-2-aminothiazole 1 was identified as an inhibitor of cyclin-dependent kinases (CDKs) by a screening of the Merck sample repository. The introduction of a methyl group at the C-5 or C-6 position on the pyrimidine ring, directed toward the gate keeper residue of CDK4 (Phe93), led to significant enhancement of selectivity for CDK4 over other CDKs. Compound 3 exhibited more than 300-fold selectivity for CDK4 over CDK1, 2, 5, 7, and 9. Subsequent improvements in aqueous solubility afforded compound 4, which is available for further in vivo studies and this compound inhibited pRb phosphorylation and BrdU incorporation in tumor models. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.04.048

文献信息

• [EN] HEMATOPOIETIC PROTECTION AGAINST CHEMOTHERAPEUTIC COMPOUNDS USING SELECTIVE CYCLIN-DEPENDENT KINASE 4/6 INHIBITORS<br/>[FR] PROTECTION HÉMATOPOÏÉTIQUE CONTRE LES COMPOSÉS CHIMIOTHÉRAPEUTIQUES AU MOYEN D'INHIBITEURS SÉLECTIFS DES KINASES DÉPENDANT DES CYCLINES 4/6
  申请人：UNIV NORTH CAROLINA

  公开号：WO2010039997A2

  公开（公告）日：2010-04-08

  Methods for reducing or preventing the effects of cytotoxic compounds in healthy cells are provided. The methods relate to the use of selective cyclin- dependent kinase (CDK) 4/6 inhibitors to induce transient quiescence in CDK4/6 dependent cells, such as hematopoietic stem cells and/or hematopoietic progenitor cells. Also described is a method of selecting compounds for reducing or preventing the effects of cytotoxic agents compounds in healthy cells.

  本文提供了减少或预防细胞毒性化合物对健康细胞影响的方法。该方法涉及使用选择性细胞周期蛋白依赖性激酶（CDK）4/6抑制剂，在CDK4/6依赖性细胞（如造血干细胞和/或造血祖细胞）中诱导短暂的静止状态。还描述了一种选择化合物以减少或预防细胞毒性化合物对健康细胞影响的方法。
• [EN] CYCLIN DEPENDENT KINASE INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS DE KINASES CYCLINE-DÉPENDANTES ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV NORTH CAROLINA

  公开号：WO2010132725A2

  公开（公告）日：2010-11-18

  The presently disclosed subject matter relates to methods and compositions for protecting healthy cells from damage due to DNA damaging agents. In particular, the presently disclosed subject matter relates to the protective action of selective cyclin dependent kinase 4/6 (CDK4/6) inhibitors administered to subjects that have been exposed to or that are at risk of exposure to DNA damage.

  目前披露的主题涉及保护健康细胞免受DNA损伤剂的损害的方法和组合物。具体而言，目前披露的主题涉及选择性环素依赖性激酶4/6（CDK4/6）抑制剂的保护作用，该抑制剂被施用于已经接触或有接触DNA损伤风险的对象身上。
• Selective Inhibitors Against Cdk4 and Cdk6 Having Aminothiazole Skeleton
  申请人：Iwasawa Yoshikazu

  公开号：US20080081811A1

  公开（公告）日：2008-04-03

  The present invention relates to a compound represented by Formula [I]: wherein X is O, S, NH or CH 2 ; Y 1 , Y 2 , Y 3 , Y 4 and Y 5 , which may be identical or different, are each CH or N; however, at least one of Y 1 , Y 2 , Y 3 , Y 4 and Y 5 is N; Z 1 and Z 2 , which may be identical or different, are each CH or N; n is an integer from 1 to 3; R 1 is a C 3 -C 8 cycloalkyl group, a C 6 -C 10 aryl group, an aliphatic heterocyclic ring or an aromatic heterocyclic ring, or a bicyclic aliphatic saturated hydrocarbon group; R 2 and R 3 , which may be identical or different, are each a hydrogen atom, a lower alkyl group, a lower alkenyl group, a C 3 -C 8 cycloalkyl group, a C 6 -C 10 aryl group, an aromatic heterocyclic ring, or the like; and R 4 is a hydrogen atom, a lower alkyl group, a C 3 -C 6 cycloalkyl group or the like, or a pharmaceutically acceptable salt or ester thereof, and a selective inhibitor against Cdk4 and/or Cdk6 or an anticancer agent containing the compound or a pharmaceutically acceptable salt or ester thereof.

  本发明涉及一种由公式[I]表示的化合物：其中X为O、S、NH或CH2；Y1、Y2、Y3、Y4和Y5可以相同也可以不同，每个为CH或N；但是，至少有一个Y1、Y2、Y3、Y4和Y5为N；Z1和Z2可以相同也可以不同，每个为CH或N；n为1至3的整数；R1为C3-C8环烷基、C6-C10芳基、脂肪族杂环环或芳香族杂环环，或双环脂肪饱和碳氢基；R2和R3可以相同也可以不同，每个为氢原子、低碳基、低烯基、C3-C8环烷基、C6-C10芳基、芳香族杂环环等；R4为氢原子、低碳基、C3-C6环烷基或类似物的药学上可接受的盐或酯，以及一种针对Cdk4和/或Cdk6的选择性抑制剂或含有该化合物或其药学上可接受的盐或酯的抗癌剂。
• SELECTIVE INHIBITORS AGAINST Cdk4 AND Cdk6 HAVING AMINOTHIAZOLE SKELETON
  申请人：BANYU PHARMACEUTICAL CO., LTD.

  公开号：EP1754706A1

  公开（公告）日：2007-02-21

  The present invention relates to a compound represented by Formula [I]: wherein X is O, S, NH or CH2; Y1, Y2, Y3, Y4 and Y5, which may be identical or different, are each CH or N; however, at least one of Y1, Y2, Y3, Y4 and Y5 is N; Z1 and Z2, which may be identical or different, are each CH or N; n is an integer from 1 to 3; R1 is a C3-C8 cycloalkyl group, a C6-C10 aryl group, an aliphatic heterocyclic ring or an aromatic heterocyclic ring, or a bicyclic aliphatic saturated hydrocarbon group; R2 and R3, which may be identical or different, are each a hydrogen atom, a lower alkyl group, a lower alkenyl group, a C3-C8 cycloalkyl group, a C6-C10 aryl group, an aromatic heterocyclic ring, or the like; and R4 is a hydrogen atom, a lower alkyl group, a C3-C6 cycloalkyl group or the like, or a pharmaceutically acceptable salt or ester thereof, and a selective inhibitor against Cdk4 and/or Cdk6 or an anticancer agent containing the compound or a pharmaceutically acceptable salt or ester thereof.

  本发明涉及一种由式 [I] 表示的化合物： 其中 X是O、S、NH或CH2； Y1、Y2、Y3、Y4 和 Y5（可以相同或不同）各自是 CH 或 N；但是，Y1、Y2、Y3、Y4 和 Y5 中至少有一个是 N； Z1 和 Z2（可以相同或不同）各自是 CH 或 N； n 是 1 至 3 的整数； R1 是 C3-C8 环烷基、C6-C10 芳基、脂肪杂环或芳香杂环或双环脂肪饱和烃基； R2 和 R3 可以相同或不同，各自是氢原子、低级烷基、低级烯基、C3-C8 环烷基、C6-C10 芳基、芳香杂环或类似基团；以及 R4 是氢原子、低级烷基、C3-C6 环烷基或类似基团、 或其药学上可接受的盐或酯，以及针对 Cdk4 和/或 Cdk6 的选择性抑制剂或含有该化合物或其药学上可接受的盐或酯的抗癌剂。
• CYCLIN DEPENDENT KINASE INHIBITORS AND METHODS OF USE
  申请人：The University of North Carolina at Chapel Hill

  公开号：EP2429566B1

  公开（公告）日：2016-01-06