N-cyclopentyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-cyclopentyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-carboxamide
• 英文别名: N-cyclopentyl-5-oxo-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxamide
• 化学式: C₁₂H₁₃N₃O₂S
• mdl: MFCD05021135
• 分子量: 263.32
• InChiKey: DNZDNKJJTWCGDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  87.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-氧代-5H-噻唑并[3,2-a]嘧啶-6-甲酸 、 环戊胺 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 16.25h， 以28%的产率得到N-cyclopentyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-carboxamide
  参考文献：
  名称：

  Allosteric Inhibition of a Mammalian Lectin

  摘要：

  Glycan-binding proteins are key components of central physiological and cellular processes such as self-/non-self-recognition, cellular tissue homing, and protein homeostasis. Herein, C-type lectins are a diverse protein family that play important roles in the immune system, rendering them attractive drug targets. To evaluate C-type lectin receptors as target proteins for small-molecule effectors, chemical probes are required, which are, however, still lacking. To overcome the supposedly poor druggability of C-type lectin receptors and to identify starting points for chemical probe development, we screened murine langerin using H-1 and F-19 NMR against a library of 871 drug-like fragments. Subsequently, hits were validated by surface plasmon resonance and enzyme-linked lectin assay. Using structure activity relationship studies and chemical synthesis, we identified thiazolopyrimidine derivatives with double-digit micromolar activity that displayed langerin selectivity. Based on H-10-N-15 HSQC NMR and competitive binding and inhibition experiments, we demonstrate that thiazolopyrimidines allosterically inhibit langerin. To the best of our knowledge, this is the first report of drug-like allosteric inhibitors of a mammalian lectin.

  DOI：

  10.1021/jacs.8b08644