2-((5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)thio)-N,N-dimethylacetamide | 1365061-43-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 2-((5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)thio)-N,N-dimethylacetamide
• 英文别名: 2-(5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)sulfanyl-N,N-dimethylacetamide
• CAS: 1365061-43-3
• 化学式: C₁₁H₁₂ClN₃OS₂
• 分子量: 301.821
• InChiKey: PEHPOIWPQJVVAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  99.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4,5-dichloro-6-methylthieno[2,3-d]pyrimidine 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 2-((5-chloro-6-methylthieno[2,3-d]pyrimidin-4-yl)thio)-N,N-dimethylacetamide
  参考文献：
  名称：

  Scaffold-hopping identifies furano[2,3-d]pyrimidine amides as potent Notum inhibitors

  摘要：

  The carboxylesterase Notum is a key negative regulator of the Wnt signaling pathway by mediating the depalmitoleoylation of Wnt proteins. Our objective was to discover potent small molecule inhibitors of Notum suitable for exploring the regulation of Wnt signaling in the central nervous system. Scaffold-hopping from thienopyrimidine acids 1 and 2, supported by X-ray structure determination, identified 3-methylimidazolin-4-one amides 20-24 as potent inhibitors of Notum with activity across three orthogonal assay formats (biochemical, extra-cellular, occupancy). A preferred example 24 demonstrated good stability in mouse microsomes and plasma, and cell permeability in the MDCK-MDR1 assay albeit with modest P-gp mediated efflux. Pharmacokinetic studies with 24 were performed in vivo in mouse with single oral administration of 24 showing good plasma exposure and reasonable CNS penetration. We propose that 24 is a new chemical tool suitable for cellular studies to explore the fundamental biology of Notum.

  DOI：

  10.1016/j.bmcl.2019.126751

文献信息

• INHIBITORS OF NOTUM PECTINACETYLESTERASE AND METHODS OF THEIR USE
  申请人：Lexicon Pharmaceuticals, Inc.

  公开号：EP2616471B1

  公开（公告）日：2014-12-31