N-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrazin-2-yl]-5-(6-methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-amine | 874476-63-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrazin-2-yl]-5-(6-methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-amine
• CAS: 874476-63-8
• 化学式: C₂₀H₂₈N₆OS₂Si
• 分子量: 460.699
• InChiKey: OBUINQXRJQAUGE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.69
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  139
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  N-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrazin-2-yl]-5-(6-methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-2-amine 在 四丁基氟化铵 、 sodium hydride 、 potassium carbonate 、 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 6.0h， 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 52.5h， 生成 N-[5-[[tert-butyl(dimethyl)silyl]oxymethyl]pyrazin-2-yl]-5-(6-methyl-2-methylsulfanylpyrimidin-4-yl)-1,3-thiazol-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

• EP1754706
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.