methyl 7-hydroxy-5-oxo-5H-<1,3>thiazolo<3,2-a>pyrimidine-6-carboxylate | 224313-88-6

• 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: methyl 7-hydroxy-5-oxo-5H-<1,3>thiazolo<3,2-a>pyrimidine-6-carboxylate
• 英文别名: methyl 7-hydroxy-5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-carboxylate；7-Hydroxy-5-oxo-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid methyl ester；methyl 7-hydroxy-5-oxo-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate
• CAS: 224313-88-6
• 化学式: C₈H₆N₂O₄S
• 分子量: 226.213
• InChiKey: JXSKXPJOBSNLGP-UHFFFAOYSA-N

物化性质

• 沸点：
  379.1±52.0 °C(Predicted)
• 密度：
  1.71±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-甲氧基色胺 、 methyl 7-hydroxy-5-oxo-5H-<1,3>thiazolo<3,2-a>pyrimidine-6-carboxylate 在 二(三甲基铝)-1,4-二氮杂二环[2.2.2]辛烷加合物 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以7%的产率得到7-hydroxy-N-(2-(5-methoxy-1H-indol-3-yl)ethyl)-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
• 作为产物：
  描述：

  2-氨基噻唑 、 甲烷三甲酸三甲酯 以 various solvent(s) 为溶剂， 反应 7.0h， 以61%的产率得到methyl 7-hydroxy-5-oxo-5H-<1,3>thiazolo<3,2-a>pyrimidine-6-carboxylate
  参考文献：
  名称：

  甲基三羧酸盐作为关键试剂，用于简单制备具有潜在生物活性的杂芳基羧酰胺。第2部分†。用2-氨基吡啶，2-氨基嘧啶，2-氨基噻唑和2-氨基苯并噻唑methanetricarboxylates的反应‡

  摘要：

  methanetricarboxylates的反应1A，B用2-氨基吡啶，2-氨基嘧啶，2-氨基噻唑，以及2-氨基苯并噻唑的产率相应的杂芳基羧酸酯类图2a，2b，5，8，图11A，B。这些杂环酯通过用伯胺获得数杂芳基酰胺的反应中用作起始材料4A-J ，6，图10A，B，13A-G轴承各种取代基上的羧酰胺基团。

  DOI：

  10.1002/jhet.5570360136

文献信息

• Allosteric Inhibition of a Mammalian Lectin
  作者：Jonas Aretz、Upendra R. Anumala、Felix F. Fuchsberger、Narges Molavi、Nandor Ziebart、Hengxi Zhang、Marc Nazaré、Christoph Rademacher

  DOI：10.1021/jacs.8b08644

  日期：2018.11.7

  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.
• Methanetricarboxylates as key reagents for the simple preparation of heteroarylcarboxamides with potential biological activity. Part 2. Reaction of methanetricarboxylates with 2-aminopyridine, 2-aminopyrimidine, 2-aminothiazole and 2-aminobenzothiazole
  作者：Alexander Kutyrev、Thomas Kappe

  DOI：10.1002/jhet.5570360136

  日期：1999.1

  The reaction of methanetricarboxylates 1a,b with 2-aminopyridine, 2-aminopyrimidine, 2-aminothiazole as well as 2-aminobenzothiazole yields corresponding heteroarylcarboxylic acid esters 2a,b, 5, 8, 11a,b. These heterocyclic esters were used as a starting material by the reaction with primary amines to obtaining a number of heteroarylcarboxylic amides 4a-j, 6, 10a,b, 13a-g bearing various substituents

  methanetricarboxylates的反应1A，B用2-氨基吡啶，2-氨基嘧啶，2-氨基噻唑，以及2-氨基苯并噻唑的产率相应的杂芳基羧酸酯类图2a，2b，5，8，图11A，B。这些杂环酯通过用伯胺获得数杂芳基酰胺的反应中用作起始材料4A-J ，6，图10A，B，13A-G轴承各种取代基上的羧酰胺基团。