3-bromoglaucine | 87167-03-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 阿朴菲
• 英文名称: 3-bromoglaucine
• 英文别名: (S)-3-Bromoglaucine；(S)-3-bromo-1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline；(6aS)-3-bromo-1,2,9,10-tetramethoxy-6-methyl-5,6,6a,7-tetrahydro-4H-dibenzo[de,g]quinoline
• CAS: 87167-03-1
• 化学式: C₂₁H₂₄BrNO₄
• 分子量: 434.33
• InChiKey: UBIRBSHOBFFLDX-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  海罂粟碱 在 N-溴代丁二酰亚胺(NBS) 作用下， 生成 3-bromoglaucine
  参考文献：
  名称：

  8-NH₂-Boldine, an Antagonist of α_1Aand α_1BAdrenoceptors without Affinity for the α_1DSubtype: Structural Requirements for Aporphines at α₁-Adrenoceptor Subtypes

  摘要：

  对21种黄酮衍生物的结构-活性分析通过检查它们对克隆人类α1A、α1B和α1D肾上腺素受体（AR）的亲和力进行，使用从稳定表达每种α1-AR亚型的鼠1皮肤成纤维细胞准备的膜。所有测试的化合物都对[125I]-HEAT结合竞争，显示出陡峭的单相曲线。最有趣的化合物是8-NH2-boldine，它对α1A-AR具有选择性亲和力（pKi = 6.37 ± 0.21），相较于α1B-AR（pKi = 5.53 ± 0.11），与1,2,9,10-四氧化黄酮表现出相似的特征，但对α1D-AR的亲和力较低（pKi < 2.5）。对存在于鼠大脑皮层的天然肾上腺素受体的结合研究确认了对人类克隆α1-AR亚型获得的结果。对α1A亚型选择性的化合物在鼠大脑皮层中区分出两个结合位点，确认该组织中存在混合的α1A和α1B-AR群体。所有化合物对[3H]-哌唑嗪结合的抑制作用比对[3H]-地尔硫卓结合的抑制作用更具选择性。在克隆α1A-AR上获得的亲和力与对去甲肾上腺素诱导的收缩或在尾动脉中的肌醇磷酸盐积累的抑制效能之间发现了密切的关系，确认在该血管中存在均匀的功能性α1A-AR群体。相反，8-NH2-boldine对克隆α1D-AR的亲和力与其作为去甲肾上腺素诱导收缩或在鼠主动脉肌醇磷酸盐积累的抑制效能之间似乎存在较差的相关性，这确认了在该血管中介导肾上腺素反应的是异质性的α1-AR群体。

  DOI：

  10.1055/s-2005-871281

文献信息

• Structure–affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: halogenation and D1 receptor selectivity
  作者：Marcelo Asencio、Claudio Hurtado-Guzmán、John J. López、Bruce K. Cassels、Philippe Protais、Abdeslam Chagraoui

  DOI：10.1016/j.bmc.2005.03.022

  日期：2005.6

  Halogenation of the aporphine alkaloid boldine at the 3-position leads to increased affinity for rat brain D-1-like dopaminergic receptors with some selectivity over D-2-like receptors. A series of 3-halogenated and 3,8-dihalogenated (halogen = Cl, Br or 1) derivatives of predicentrine (9-O-methylboldine) and glaucine (2,9-di-O-methylboldine) were prepared and assayed for binding at D-1 and D-2 sites. Halogenation of predicentrine led to strong increases in affinity for D-1-like receptors, while the affinities for D-2-like receptors were either practically unchanged or reduced three- to fourfold. Halogenated glaucine derivatives did not show any clear trend towards enhanced selectivity, and the affinities were poor and similar to or worse than the values previously recorded for glaucine itself. Together with earlier work on boldine derivatives, these results suggest that the 2-hydroxy group on the aporphine skeleton may determine a binding mode favoring D-1-like over D-2-like receptors, with enhanced affinity when the C-3 position is halogenated. (c) 2005 Elsevier Ltd. All rights reserved.
• Bhakuni, Dewan S.; Jain, Sudha; Singh, Meenakshi, Heterocycles, 1989, vol. 28, # 1, p. 315 - 320
  作者：Bhakuni, Dewan S.、Jain, Sudha、Singh, Meenakshi

  DOI：——

  日期：——
• Synthesis and properties of glaucine-quinol
  作者：S. Philipov、O. Petrov、N. Mollov

  DOI：10.1016/s0040-4020(01)88694-4

  日期：1983.1
• 8-NH₂-Boldine, an Antagonist of α_1Aand α_1BAdrenoceptors without Affinity for the α_1DSubtype: Structural Requirements for Aporphines at α₁-Adrenoceptor Subtypes
  作者：M. Dolores Ivorra、Miguel Valiente、Sonia Martínez、Yolanda Madrero、M. Antonia Noguera、Bruce K. Cassels、Eduardo M. Sobarzo、Pilar D’Ocon

  DOI：10.1055/s-2005-871281

  日期：2005.8

  Structure-activity analysis of 21 aporphine derivatives was performed by examining their affinities for cloned human α1A, α1B and α1D adrenoceptors (AR) using membranes prepared from rat-1 fibroblasts stably expressing each α1-AR subtype. All the compounds tested competed for [125 I]-HEAT binding with steep and monophasic curves. The most interesting compound was 8-NH2-boldine, which retains the selective affinity for α 1A-AR (pKi = 6.37 ± 0.21) vs. α 1B-AR (pKi = 5.53 ± 0.11) exhibited by 1,2,9,10-tetraoxygenated aporphines, but shows low affinity for α 1D-AR (pKi < 2.5). Binding studies on native adrenoceptors present in rat cerebral cortex confirms the results obtained for human cloned α1-AR subtypes. The compounds selective for the α1A subtype discriminate two binding sites in rat cerebral cortex confirming a mixed population of α1A- and α1B-AR in this tissue. All compounds are more selective as inhibitors of [3 H]-prazosin binding than of [3 H]-diltiazem binding to rat cerebral cortical membranes. A close relationship was found between affinities obtained for cloned α1A-AR and inhibitory potencies on noradrenaline-induced contraction or inositol phosphate accumulation in tail artery, confirming that there is a homogeneous functional population of α 1A-AR in this vessel. On the contrary, a poor correlation seems to exist between the affinity of 8-NH2-boldine for cloned α1D-AR and its potency as an inhibitor of noradrenaline-induced contraction or inositol phosphate accumulation in rat aorta, which confirms that a heterogeneous population of α1-AR mediates the adrenergic response in this vessel.

  对21种黄酮衍生物的结构-活性分析通过检查它们对克隆人类α1A、α1B和α1D肾上腺素受体（AR）的亲和力进行，使用从稳定表达每种α1-AR亚型的鼠1皮肤成纤维细胞准备的膜。所有测试的化合物都对[125I]-HEAT结合竞争，显示出陡峭的单相曲线。最有趣的化合物是8-NH2-boldine，它对α1A-AR具有选择性亲和力（pKi = 6.37 ± 0.21），相较于α1B-AR（pKi = 5.53 ± 0.11），与1,2,9,10-四氧化黄酮表现出相似的特征，但对α1D-AR的亲和力较低（pKi < 2.5）。对存在于鼠大脑皮层的天然肾上腺素受体的结合研究确认了对人类克隆α1-AR亚型获得的结果。对α1A亚型选择性的化合物在鼠大脑皮层中区分出两个结合位点，确认该组织中存在混合的α1A和α1B-AR群体。所有化合物对[3H]-哌唑嗪结合的抑制作用比对[3H]-地尔硫卓结合的抑制作用更具选择性。在克隆α1A-AR上获得的亲和力与对去甲肾上腺素诱导的收缩或在尾动脉中的肌醇磷酸盐积累的抑制效能之间发现了密切的关系，确认在该血管中存在均匀的功能性α1A-AR群体。相反，8-NH2-boldine对克隆α1D-AR的亲和力与其作为去甲肾上腺素诱导收缩或在鼠主动脉肌醇磷酸盐积累的抑制效能之间似乎存在较差的相关性，这确认了在该血管中介导肾上腺素反应的是异质性的α1-AR群体。