10-ethyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid | 897771-21-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并硫氮卓类
• 英文名称: 10-ethyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid
• 英文别名: 5-ethyl-6-oxobenzo[b][1,4]benzothiazepine-3-carboxylic acid
• CAS: 897771-21-0
• 化学式: C₁₆H₁₃NO₃S
• mdl: MFCD03830268
• 分子量: 299.35
• InChiKey: IJWLQWNUKAKIKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  10-ethyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid 在 4-二甲氨基吡啶 、 双氧水 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 10-ethyl-11-oxo-N-phenyl-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxamide 5-oxide
  参考文献：
  名称：

  Discovery, Optimization, and Characterization of Novel D₂ Dopamine Receptor Selective Antagonists

  摘要：

  The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for neuropsychiatric and endocrine disorders. However, clinically approved drugs targeting 02 DAR display poor selectivity between the D2 and other receptors, especially the D3 DAR This lack of selectivity may lead to undesirable side effects. Here we describe the chemical and pharmacological characterization of a novel 02 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5 receptor selectivity. The final probe 65 was obtained through a quantitative high-throughput screening campaign, followed by medicinal chemistry optimization, to yield a selective molecule with good in vitro physical properties, metabolic stability, and in vivo pharmacokinetics. The optimized molecule may be a useful in vivo probe for studying D2 DAR signal modulation and could also serve as a lead compound for the development of D2 DAR-selective druglike molecules for the treatment of multiple neuropsychiatric and endocrine disorders.

  DOI：

  10.1021/jm500126s
• 作为产物：
  描述：

  11-氧代-10,11-二氢二苯并[B,F][1,4]硫氮杂-8-羧酸 、 碘乙烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以88%的产率得到10-ethyl-11-oxo-10,11-dihydrodibenzo[b,f][1,4]thiazepine-8-carboxylic acid
  参考文献：
  名称：

  Discovery, Optimization, and Characterization of Novel D₂ Dopamine Receptor Selective Antagonists

  摘要：

  The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for neuropsychiatric and endocrine disorders. However, clinically approved drugs targeting 02 DAR display poor selectivity between the D2 and other receptors, especially the D3 DAR This lack of selectivity may lead to undesirable side effects. Here we describe the chemical and pharmacological characterization of a novel 02 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5 receptor selectivity. The final probe 65 was obtained through a quantitative high-throughput screening campaign, followed by medicinal chemistry optimization, to yield a selective molecule with good in vitro physical properties, metabolic stability, and in vivo pharmacokinetics. The optimized molecule may be a useful in vivo probe for studying D2 DAR signal modulation and could also serve as a lead compound for the development of D2 DAR-selective druglike molecules for the treatment of multiple neuropsychiatric and endocrine disorders.

  DOI：

  10.1021/jm500126s