[[2-(acetylamino)-5-thiazolyl]thio]Acetic Acid 1,1-dimethylethyl Ester | 224441-67-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: [[2-(acetylamino)-5-thiazolyl]thio]Acetic Acid 1,1-dimethylethyl Ester
• 英文别名: Tert-butyl 2-[(2-acetamido-1,3-thiazol-5-yl)sulfanyl]acetate
• CAS: 224441-67-2
• 化学式: C₁₁H₁₆N₂O₃S₂
• 分子量: 288.392
• InChiKey: HOEMOEJHHVVLJW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  122
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [[2-(acetylamino)-5-thiazolyl]thio]Acetic Acid 1,1-dimethylethyl Ester 在 乙醚 作用下， 以 二氯甲烷 、 三氟乙酸 为溶剂， 反应 16.0h， 以to afford the desired product (3.38 g, 97%) as a solid, mp 210° C.的产率得到(2-acetylamino-thiazol-5-ylmercapto)-acetic acid
  参考文献：
  名称：

  Aminothiazole inhibitors of cyclin dependent kinases

  摘要：

  本发明描述了I式化合物及其药学上可接受的盐，其中R1、R2、R3、R4、R5、m和n如规范中所定义。I式化合物是蛋白激酶抑制剂，可用于治疗增殖性疾病，例如癌症、炎症和关节炎。它们也可能对治疗阿尔茨海默病、化疗引起的脱发和心血管疾病有用。

  公开号：

  US06521759B2
• 作为产物：
  描述：

  2-acetylamino-5-acetylthiothiazole 、 溴乙酸叔丁酯 在 potassium tert-butylate 作用下， 生成 [[2-(acetylamino)-5-thiazolyl]thio]Acetic Acid 1,1-dimethylethyl Ester
  参考文献：
  名称：

  Discovery of Aminothiazole Inhibitors of Cyclin-Dependent Kinase 2:  Synthesis, X-ray Crystallographic Analysis, and Biological Activities

  摘要：

  High throughput screening identified 2-acetamido-thiazolylthio acetic ester 1 as an inhibitor of cyclin-dependent kinase 2 (CDK2). Because this compound is inactive in cells and unstable in plasma, we have stabilized it to metabolic hydrolysis by replacing the ester moiety with a 5-ethyl-substituted oxazole as in compound 14. Combinatorial and parallel synthesis provided a rapid analysis of the structure-activity relationship (SAR) for these inhibitors of CDK2, and over 100 analogues with IC50 values in the 1-10 nM range were rapidly prepared. The X-ray crystallographic data of the inhibitors bound to the active site of CDK2 protein provided insight into the binding modes of these inhibitors, and the SAR of this series of analogues was rationalized. Many of these analogues displayed potent and broad spectrum antiproliferative activity across a panel of tumor cell lines in vitro. In addition, A2780 ovarian carcinoma cells undergo rapid apoptosis following exposure to CDK2 inhibitors of this class. Mechanism of action studies have confirmed that the phosphorylation of CDK2 substrates such as RB, histone H1, and DNA polymerase alpha (p70 subunit) is reduced in the presence of compound 14. Further optimization led to compounds such as water soluble 45, which possesses a favorable pharmacokinetic profile in mice and demonstrates significant antitumor activity in vivo in several murine and human models, including an engineered murine mammary tumor that overexpresses cyclin E, the coactivator of CDK2.

  DOI：

  10.1021/jm0201520

文献信息

• AMINOTHIAZOLE INHIBITORS OF CYCLIN DEPENDENT KINASES
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：EP1042307A1

  公开（公告）日：2000-10-11
• EP1042307A4
  申请人：——

  公开号：EP1042307A4

  公开（公告）日：2003-01-29
• US6040321A
  申请人：——

  公开号：US6040321A

  公开（公告）日：2000-03-21
• US6262096B1
  申请人：——

  公开号：US6262096B1

  公开（公告）日：2001-07-17
• US6521759B2
  申请人：——

  公开号：US6521759B2

  公开（公告）日：2003-02-18