[5-[[5-(6-Methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]amino]pyrazin-2-yl]methanol | 874476-62-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: [5-[[5-(6-Methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]amino]pyrazin-2-yl]methanol
• CAS: 874476-62-7
• 化学式: C₁₄H₁₄N₆OS₂
• 分子量: 346.437
• InChiKey: VGQOUAHNFNXOIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  150
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [5-[[5-(6-Methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]amino]pyrazin-2-yl]methanol 在 咪唑 、 四丁基氟化铵 、 sodium hydride 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成
  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
• 作为产物：
  描述：

  (5-溴乙基吡嗪-2-基)氨基甲酸叔丁酯 在 咪唑 、 sodium hydroxide 、 18-冠醚-6 、 potassium carbonate 、 对甲苯磺酸 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 氯仿 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 49.5h， 生成 [5-[[5-(6-Methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-yl]amino]pyrazin-2-yl]methanol
  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

• 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。
• EP1754706
  申请人：——

  公开号：——

  公开（公告）日：——
• US7709475B2
  申请人：——

  公开号：US7709475B2

  公开（公告）日：2010-05-04
• Identification of potent 5-pyrimidinyl-2-aminothiazole CDK4, 6 inhibitors with significant selectivity over CDK1, 2, 5, 7, and 9
  作者：Tadashi Shimamura、Jun Shibata、Hideki Kurihara、Takashi Mita、Sachie Otsuki、Takeshi Sagara、Hiroshi Hirai、Yoshikazu Iwasawa

  DOI：10.1016/j.bmcl.2006.04.048

  日期：2006.7

  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.