3-(dimethylamino)-2-methyl-1-(4-methyl-2-(methylamino)thiazol-5-yl)prop-2-en-1-one | 1421693-15-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(dimethylamino)-2-methyl-1-(4-methyl-2-(methylamino)thiazol-5-yl)prop-2-en-1-one
• CAS: 1421693-15-3
• 化学式: C₁₁H₁₇N₃OS
• 分子量: 239.341
• InChiKey: OTYQJFKNXOQJKK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.14
• 重原子数：
  16.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  45.23
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-(dimethylamino)-2-methyl-1-(4-methyl-2-(methylamino)thiazol-5-yl)prop-2-en-1-one 、 1-(3-(4-(methylsulfonyl)piperazin-1-yl)phenyl)guanidine 以 乙二醇甲醚 为溶剂， 以12%的产率得到N,4-dimethyl-5-(5-methyl-2-((3-(4-(methylsulfonyl)piperazin-1-yl)phenyl)amino) pyrimidin-4-yl)thiazol-2-amine
  参考文献：
  名称：

  Structure-based design of highly selective 2,4,5-trisubstituted pyrimidine CDK9 inhibitors as anti-cancer agents

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113244

文献信息

• Substituted 4-(Thiazol-5-yl)-2-(phenylamino)pyrimidines Are Highly Active CDK9 Inhibitors: Synthesis, X-ray Crystal Structures, Structure–Activity Relationship, and Anticancer Activities
  作者：Hao Shao、Shenhua Shi、Shiliang Huang、Alison J. Hole、Abdullahi Y. Abbas、Sonja Baumli、Xiangrui Liu、Frankie Lam、David W. Foley、Peter M. Fischer、Martin Noble、Jane A. Endicott、Chris Pepper、Shudong Wang

  DOI：10.1021/jm301475f

  日期：2013.2.14

  Cancer cells often have a high demand for antiapoptotic proteins in order to resist programmed cell death. CDK9 inhibition selectively targets survival proteins and reinstates apoptosis in cancer cells. We designed a series of 4-thiazol-2-anilinopyrimidine derivatives with functional groups attached to the CS-position of the pyrimidine or to the C4-thiazol moiety and investigated their effects on CDK9 potency and selectivity. One of the most selective compounds, 12u inhibits CDK9 with IC50 = 7 nM and shows over 80-fold selectivity for CDK9 versus CDK2. X-ray crystal structures of 12u bound to CDK9 and CDK2 provide insights into the binding modes. This work, together with crystal structures of selected inhibitors in complex with both enzymes described in a companion paper,(34) provides a rationale for the observed SAR. 12u demonstrates potent anticancer activity against primary chronic lymphocytic leukemia cells with a therapeutic window 31- and 107-fold over those of normal B-and T-cells.