benzyl 1,2,3,4,4a,5-hexahydro-1H-pyrazino[2,1-c][1,4]benzoxazine-1-one-3-carboxylate | 167024-12-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: benzyl 1,2,3,4,4a,5-hexahydro-1H-pyrazino[2,1-c][1,4]benzoxazine-1-one-3-carboxylate
• 英文别名: Benzyl 1-oxo-2,4,4a,5-tetrahydropyrazino[2,1-c][1,4]benzoxazine-3-carboxylate
• CAS: 167024-12-6
• 化学式: C₁₉H₁₈N₂O₄
• 分子量: 338.363
• InChiKey: CRKHKHFVZLXYAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  benzyl 1,2,3,4,4a,5-hexahydro-1H-pyrazino[2,1-c][1,4]benzoxazine-1-one-3-carboxylate 在 palladium on activated charcoal 硼烷四氢呋喃络合物 、 1,4-环己二烯 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 嗪并[2,1-c][1,4]苯并恶嗪,1,2,3,4,4一个-1,5-六氢-(9CL)
  参考文献：
  名称：

  Hindered rotation congeners of mazapertine: High affinity ligands for the 5-HT1A receptor

  摘要：

  Hindered rotation analogs of the antipsychotic mazapertine (1) were prepared. These compounds exhibited high affinity for the 5-HT1A receptor, but not for other serotonin or dopamine receptors. The related beta-carboline structures were also synthesized and were found to be potent 5-HT1A ligands. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00074-7
• 作为产物：
  描述：

  C-(3,4-二氢-2H-苯并[1,4]嗪-3-基)-甲胺 在 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 144.0h， 生成 benzyl 1,2,3,4,4a,5-hexahydro-1H-pyrazino[2,1-c][1,4]benzoxazine-1-one-3-carboxylate
  参考文献：
  名称：

  New Pyrimido[5,4-b]indoles as Ligands for α₁-Adrenoceptor Subtypes

  摘要：

  A new series of compounds were designed as structural analogues of the alpha(1)-AR ligand RN5 (4), characterized by a tricyclic 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione system connected through an alkyl. chain to a phenylpiperazine (PP) moiety. These compounds were synthesized and tested in binding assays on human alpha(1A)-AR, alpha(1B)-AR, and alpha(1D)-AR subtypes expressed in HEK293 cells. Several structural modifications were performed on the PP moiety, the tricyclic system, and the connecting alkyl chain. Many of the new molecules showed a preferential affinity for the alpha(1D)-AR subtype. Some compounds, including 39 and 40, displayed substantial alpha(1D)-AR selectivity with respect to alpha(1A)-AR, alpha(1B)-AR, serotonergic 5-HT1A, 5-HT1B, 5-HT2A, and dopaminergic D-1 and D-2 receptors. Two conformationally rigid analogues of 4, useful for studying the architecture of the receptor/ligand complex, were also prepared and tested. A subset of the new compounds was then used to evolve a preliminary pharmacophore model for alpha(1D)-AR antagonists, based on a more generalized model we had developed for alpha(1)-AR antagonists. This new model rationalized the relationships between structural properties and biological data of the pyrimido[5,4-b]indole compounds, as well as other compounds.

  DOI：

  10.1021/jm0307741

文献信息

• New Pyrimido[5,4-<i>b</i>]indoles as Ligands for α₁-Adrenoceptor Subtypes
  作者：Giuseppe Romeo、Luisa Materia、Fabrizio Manetti、Alfredo Cagnotto、Tiziana Mennini、Ferdinando Nicoletti、Maurizio Botta、Filippo Russo、Kenneth P. Minneman

  DOI：10.1021/jm0307741

  日期：2003.7.1

  A new series of compounds were designed as structural analogues of the alpha(1)-AR ligand RN5 (4), characterized by a tricyclic 5H-pyrimido[5,4-b]indole-(1H,3H)2,4-dione system connected through an alkyl. chain to a phenylpiperazine (PP) moiety. These compounds were synthesized and tested in binding assays on human alpha(1A)-AR, alpha(1B)-AR, and alpha(1D)-AR subtypes expressed in HEK293 cells. Several structural modifications were performed on the PP moiety, the tricyclic system, and the connecting alkyl chain. Many of the new molecules showed a preferential affinity for the alpha(1D)-AR subtype. Some compounds, including 39 and 40, displayed substantial alpha(1D)-AR selectivity with respect to alpha(1A)-AR, alpha(1B)-AR, serotonergic 5-HT1A, 5-HT1B, 5-HT2A, and dopaminergic D-1 and D-2 receptors. Two conformationally rigid analogues of 4, useful for studying the architecture of the receptor/ligand complex, were also prepared and tested. A subset of the new compounds was then used to evolve a preliminary pharmacophore model for alpha(1D)-AR antagonists, based on a more generalized model we had developed for alpha(1)-AR antagonists. This new model rationalized the relationships between structural properties and biological data of the pyrimido[5,4-b]indole compounds, as well as other compounds.
• Hindered rotation congeners of mazapertine: High affinity ligands for the 5-HT1A receptor
  作者：Ellen W. Baxter、Allen B. Reitz

  DOI：10.1016/s0960-894x(97)00074-7

  日期：1997.1

  Hindered rotation analogs of the antipsychotic mazapertine (1) were prepared. These compounds exhibited high affinity for the 5-HT1A receptor, but not for other serotonin or dopamine receptors. The related beta-carboline structures were also synthesized and were found to be potent 5-HT1A ligands. (C) 1997 Elsevier Science Ltd.