(+)-Cyclazosin | 139953-73-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (+)-Cyclazosin
• 英文别名: Cyclazosin；[(4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)-2,3,4a,5,6,7,8,8a-octahydroquinoxalin-1-yl]-(furan-2-yl)methanone
• CAS: 139953-73-4
• 化学式: C₂₃H₂₇N₅O₄
• 分子量: 437.498
• InChiKey: XBRXTUGRUXGBPX-DLBZAZTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  benzyl (4aR,8aS)-4-(4-amino-6,7-dimethoxyquinazolin-2-yl)octahydroquinoxaline-1(2H)-carboxylate hydrochloride 在 palladium on activated charcoal 三乙胺 、 环己烯 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 9.0h， 生成 (+)-Cyclazosin
  参考文献：
  名称：

  Synthesis and α1-adrenoceptor antagonist activity of derivatives and isosters of the furan portion of (+)-cyclazosin

  摘要：

  alpha(1)-Adrenoceptor selective antagonists are crucial in investigating the role and biological functions of alpha(1)-adrenoceptor subtypes. We synthesized and studied the alpha(1)-adrenoceptor blocking properties of new molecules structurally related to the alpha(1B)-adrenoceptor selective antagonist (+)-cyclazosin, in an attempt to improve its receptor selectivity. In particular, we investigated the importance of substituents introduced at position 5 of the 2-furan moiety of (+)-cyclazosin and its replacement with classical isosteric rings. The 5-methylfuryl derivative (+)-3, [(+)-metcyclazosin], improved the pharmacological properties of the progenitor, displaying a competitive antagonism and an 11 fold increased selectivity for alpha(1B) over alpha(1A), while maintaining a similar selectivity for the alpha(1B)-adrenoceptor relative to the alpha(1D)-adrenoceptor. Compound (+)-3 may represent a useful tool for alpha(1B)-adrenoceptor characterization in functional studies. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.01.028

文献信息

• Synthesis and α1-adrenoceptor antagonist activity of derivatives and isosters of the furan portion of (+)-cyclazosin
  作者：Gianni Sagratini、Piero Angeli、Michela Buccioni、Ugo Gulini、Gabriella Marucci、Carlo Melchiorre、Amedeo Leonardi、Elena Poggesi、Dario Giardinà

  DOI：10.1016/j.bmc.2007.01.028

  日期：2007.3

  alpha(1)-Adrenoceptor selective antagonists are crucial in investigating the role and biological functions of alpha(1)-adrenoceptor subtypes. We synthesized and studied the alpha(1)-adrenoceptor blocking properties of new molecules structurally related to the alpha(1B)-adrenoceptor selective antagonist (+)-cyclazosin, in an attempt to improve its receptor selectivity. In particular, we investigated the importance of substituents introduced at position 5 of the 2-furan moiety of (+)-cyclazosin and its replacement with classical isosteric rings. The 5-methylfuryl derivative (+)-3, [(+)-metcyclazosin], improved the pharmacological properties of the progenitor, displaying a competitive antagonism and an 11 fold increased selectivity for alpha(1B) over alpha(1A), while maintaining a similar selectivity for the alpha(1B)-adrenoceptor relative to the alpha(1D)-adrenoceptor. Compound (+)-3 may represent a useful tool for alpha(1B)-adrenoceptor characterization in functional studies. (c) 2007 Elsevier Ltd. All rights reserved.