5-(羟基甲基)吡嗪-2-氨基甲酸叔丁酯 | 874476-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5-(羟基甲基)吡嗪-2-氨基甲酸叔丁酯
• 英文名称: tert-Butyl (5-(hydroxymethyl)pyrazin-2-yl)carbamate
• 英文别名: tert-butyl N-[5-(hydroxymethyl)pyrazin-2-yl]carbamate
• CAS: 874476-55-8
• 化学式: C₁₀H₁₅N₃O₃
• mdl: MFCD09952117
• 分子量: 225.247
• InChiKey: VLZKMTFRXYTMGF-UHFFFAOYSA-N

物化性质

• 沸点：
  326.9±42.0 °C(Predicted)
• 密度：
  1.260±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.3
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-(羟基甲基)吡嗪-2-氨基甲酸叔丁酯 在 咪唑 、 三氟乙酸 作用下， 以 四氢呋喃 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.0h， 生成 N-[[5-[[tert-butyl(diphenyl)silyl]oxymethyl]pyrazin-2-yl]carbamothioyl]benzamide
  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 sodium hydroxide 、 18-冠醚-6 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 13.0h， 生成 5-(羟基甲基)吡嗪-2-氨基甲酸叔丁酯
  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。
• 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.