3-propionylamino-chroman-4-one | 64139-25-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 3-propionylamino-chroman-4-one
• 英文别名: 3-Propionylamino-4-chromanon；N-(4-oxo-2,3-dihydrochromen-3-yl)propanamide
• CAS: 64139-25-9
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: UNWJKPXUHZXVSR-UHFFFAOYSA-N

物化性质

• 沸点：
  461.2±45.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-propionylamino-chroman-4-one 在 10percent Pd/C lithium aluminium tetrahydride 、 氢气 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 0.5h， 生成 3-(N-n-propyl-N-propionylamino)-3,4-dihydro-2H-[1]benzopyran
  参考文献：
  名称：

  Thiazoloindans and Thiazolobenzopyrans:  A Novel Class of Orally Active Central Dopamine (Partial) Agonists

  摘要：

  The 2-aminothiazole moiety has proven its value in medicinal chemistry as a stable and lipophilic bioisosteric replacement of a phenol group. This approach has provided dopamine (DA) agonists with good oral availability. To further explore its use in the development of DA agonists, we have combined the 2-aminothiazole moiety with 2-aminoindans and 3-aminobenzopyrans, which are known templates for DA agonists. In this study we have synthesized 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-thiazole[5,4-f]-[1]benzopyran (12) and 6-amino-2-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (20) and several analogues (13, 17, and 21). The affinity of the thiazolobenzopyrans and thiazoloindans for DA receptors was evaluated, which revealed compound 20 to have high affinity for DA DQ receptors. In addition, the compounds were screened for their potential to inhibit lipid peroxidation, to determine their radical scavenging properties. Compounds 12, 20, and 21 were subjected to further pharmacological evaluation in a functional assay to determine intrinsic activity. Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists). These studies selected compound 20 (GMC 1111) as particularly interesting. Compound 20 caused a rotation activation in unilaterally B-OH-DA lesioned rats and an increase in DA turnover in rat striatum. This dual agonist/antagonist action is best accounted for by its partial agonism at striatal DA D-2 receptors. Interestingly, 20 displayed long-lasting activity and excellent oral availability in B-OH-DA lesioned rats, making this compound potentially useful for the treatment of Parkinson's disease.

  DOI：

  10.1021/jm000087z
• 作为产物：
  描述：

  丙酰氯 、 3-amino-4-chromanone hydrochloride 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 3-propionylamino-chroman-4-one
  参考文献：
  名称：

  Thiazoloindans and Thiazolobenzopyrans:  A Novel Class of Orally Active Central Dopamine (Partial) Agonists

  摘要：

  The 2-aminothiazole moiety has proven its value in medicinal chemistry as a stable and lipophilic bioisosteric replacement of a phenol group. This approach has provided dopamine (DA) agonists with good oral availability. To further explore its use in the development of DA agonists, we have combined the 2-aminothiazole moiety with 2-aminoindans and 3-aminobenzopyrans, which are known templates for DA agonists. In this study we have synthesized 6-amino-3-(N,N-di-n-propylamino)-3,4-dihydro-2H-thiazole[5,4-f]-[1]benzopyran (12) and 6-amino-2-(N,N-di-n-propylamino)thiazolo[4,5-f]indan (20) and several analogues (13, 17, and 21). The affinity of the thiazolobenzopyrans and thiazoloindans for DA receptors was evaluated, which revealed compound 20 to have high affinity for DA DQ receptors. In addition, the compounds were screened for their potential to inhibit lipid peroxidation, to determine their radical scavenging properties. Compounds 12, 20, and 21 were subjected to further pharmacological evaluation in a functional assay to determine intrinsic activity. Compound 20 was also studied with microdialysis (to determine effects on DA turnover in striatum) and in unilaterally 6-OH-DA lesioned rats (to determine their potential as DA agonists). These studies selected compound 20 (GMC 1111) as particularly interesting. Compound 20 caused a rotation activation in unilaterally B-OH-DA lesioned rats and an increase in DA turnover in rat striatum. This dual agonist/antagonist action is best accounted for by its partial agonism at striatal DA D-2 receptors. Interestingly, 20 displayed long-lasting activity and excellent oral availability in B-OH-DA lesioned rats, making this compound potentially useful for the treatment of Parkinson's disease.

  DOI：

  10.1021/jm000087z