3-(2-hydroxyethyl)-2-ethyl-5H-pyrimido[5,4-b]indole-(3H)4-one | 583828-71-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 3-(2-hydroxyethyl)-2-ethyl-5H-pyrimido[5,4-b]indole-(3H)4-one
• 英文别名: 2-ethyl-3-(2-hydroxyethyl)-5H-pyrimido[5,4-b]indol-4-one
• CAS: 583828-71-1
• 化学式: C₁₄H₁₅N₃O₂
• 分子量: 257.292
• InChiKey: RHMMSEMBZZAJSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  68.7
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(2-hydroxyethyl)-2-ethyl-5H-pyrimido[5,4-b]indole-(3H)4-one 在 氯化亚砜 作用下， 以 甲苯 为溶剂， 反应 2.5h， 生成 3-[2-[4-(2-ethoxyphenyl)piperazin-1-yl]ethyl]-2-ethyl-5H-pyrimido[5,4-b]indole-(3H)4-one
  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
• 作为产物：
  描述：

  C.I.酸性橙108 、 ethyl 3-[(ethoxypropyliden)amino]-1H-indole-2-carboxylate 反应 7.0h， 以77%的产率得到3-(2-hydroxyethyl)-2-ethyl-5H-pyrimido[5,4-b]indole-(3H)4-one
  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.