2-tert-butyl-4-methyl-1,2,5-thiadiazol-3-one | 472965-76-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-tert-butyl-4-methyl-1,2,5-thiadiazol-3-one
• 英文别名: 2-Tert-butyl-4-methyl-1,2,5-thiadiazol-3-one
• CAS: 472965-76-7
• 化学式: C₇H₁₂N₂OS
• 分子量: 172.251
• InChiKey: CUAWXSBTSWRKIV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  58
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-tert-butyl-4-methyl-1,2,5-thiadiazol-3-one 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.0h， 生成 methyl 3-(2-tert-butyl-3-oxo-1,2,5-thiadiazol-4-yl)-2-formamido-2-methoxycarbonyl propionate
  参考文献：
  名称：

  2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors

  摘要：

  In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed using a Crownpac CR(+) column affording (R)- and (S)-TDPA of high enantiomeric purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed that the early eluting enantiomer has R-configuration. Both enantiomers showed high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, determined using a [H-3]AMPA binding assay and an electrophysiological model, respectively. The affinities and agonist activities obtained for (R)-TDPA (IC50=0.265 muM and EC50-6.6 muM, respectively) and (S)-TDPA (IC50=0.0065 muM and EC50=20 muM. respectively) revealed a remarkably low AMPA receptor stereoselectivity. (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu uptake sites displacing [H-3](R)-aspartic acid (IC(50)approximate to390 muM). An enantiospecific and subtype-selective agonist activity was observed for (S)-TDPA at group I metabotropic Glu (mGlu) receptors (EC50-13 muM at mGlu(5) and EC50=95 muM at mGlu(1)). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00041-x
• 作为产物：
  描述：

  3-hydroxy-4-methyl-1,2,5-thiadiazole 、 醋酸叔丁酯 在 Amberlyst 15 作用下， 反应 14.0h， 以71%的产率得到2-tert-butyl-4-methyl-1,2,5-thiadiazol-3-one
  参考文献：
  名称：

  2-Amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid: resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors

  摘要：

  In order to identify new subtype-selective (S)-glutamate (Glu) receptor ligands we have synthesized (RS)-2-amino-3-(3-hydroxy-1,2,5-thiadiazol-4-yl)propionic acid [(RS)-TDPA]. Resolution of (RS)-TDPA by chiral chromatography was performed using a Crownpac CR(+) column affording (R)- and (S)-TDPA of high enantiomeric purity (enantiomeric excess=99.9%). An X-ray crystallographic analysis revealed that the early eluting enantiomer has R-configuration. Both enantiomers showed high affinity as well as high agonist activity at (RS)-2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) receptors, determined using a [H-3]AMPA binding assay and an electrophysiological model, respectively. The affinities and agonist activities obtained for (R)-TDPA (IC50=0.265 muM and EC50-6.6 muM, respectively) and (S)-TDPA (IC50=0.0065 muM and EC50=20 muM. respectively) revealed a remarkably low AMPA receptor stereoselectivity. (S)-TDPA showing the highest affinity and (R)-TDPA the most potent agonist activity. In addition, (S)-TDPA was shown to interact with synaptosomal Glu uptake sites displacing [H-3](R)-aspartic acid (IC(50)approximate to390 muM). An enantiospecific and subtype-selective agonist activity was observed for (S)-TDPA at group I metabotropic Glu (mGlu) receptors (EC50-13 muM at mGlu(5) and EC50=95 muM at mGlu(1)). (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00041-x