9-bromo-8-oxo-1,5,6,8-tetrahydro-2H,4H-1,5-methano-pyrido[1,2-a][1,5]diazocine-3-carboxylic acid tert-butyl ester [3-bromo-N-tboc-cytisine] | 207390-11-2

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: 9-bromo-8-oxo-1,5,6,8-tetrahydro-2H,4H-1,5-methano-pyrido[1,2-a][1,5]diazocine-3-carboxylic acid tert-butyl ester [3-bromo-N-tboc-cytisine]
• 英文别名: N-Boc-9-bromocytisine；9-bromo-8-oxo-1,5,6,8-tetrahydro-2H,4H-1,5-methano-pyrido[1,2-a][1,5]diazocine-3-carboxylic acid tert-butyl ester
• CAS: 207390-11-2
• 化学式: C₁₆H₂₁BrN₂O₃
• 分子量: 369.258
• InChiKey: HNTYDHQAOYCCFP-WDEREUQCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.97
• 重原子数：
  22.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  51.54
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  9-bromo-8-oxo-1,5,6,8-tetrahydro-2H,4H-1,5-methano-pyrido[1,2-a][1,5]diazocine-3-carboxylic acid tert-butyl ester [3-bromo-N-tboc-cytisine] 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 1.17h， 生成 9-phenyl-1,2,3,4,5,6-hexahydro-1,5-methano-pyridino[1,2-a]diazocin-8-one [3-phenyl-cytisine]
  参考文献：
  名称：

  WO2007/100430

  摘要：

  公开号：
• 作为产物：
  描述：

  N-Boc-cytisine 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 以57%的产率得到9-bromo-8-oxo-1,5,6,8-tetrahydro-2H,4H-1,5-methano-pyrido[1,2-a][1,5]diazocine-3-carboxylic acid tert-butyl ester [3-bromo-N-tboc-cytisine]
  参考文献：
  名称：

  Identification of 9-fluoro substituted (−)-cytisine derivatives as ligands with high affinity for nicotinic receptors

  摘要：

  (-)-9-氟赛替新、(-)-9-甲基赛替新和(-)-9-三氟甲基赛替新是从天然产物(-)-赛替新合成的。9-甲基和9-三氟甲基赛替新在α(4)β(2)烟碱型乙酰胆碱受体亚型上显示出显著的亲和力（0.2 nM），并且相对于α(7)烟碱型乙酰胆碱受体亚型具有高选择性。亲和力值的比较表明，在(-)-赛替新的9位取代基的大小似乎比电子因素更重要，以实现对α(4)β(2)烟碱型乙酰胆碱受体的高效结合和选择性。©2010 Elsevier Ltd. 保留所有权利。

  DOI：

  10.1016/j.bmcl.2010.09.017

文献信息

• Synthesis and Pharmacological Evaluation of Novel 9- and 10-Substituted Cytisine Derivatives. Nicotinic Ligands of Enhanced Subtype Selectivity
  作者：Sheela K. Chellappan、Yingxian Xiao、Werner Tueckmantel、Kenneth J. Kellar、Alan P. Kozikowski

  DOI：10.1021/jm051196m

  日期：2006.5.1

  We report the synthesis and pharmacological properties of several cytisine derivatives. Among them, two 10-substituted derivatives showed much higher selectivities for the alpha4beta2 nAChR subtype in binding assays than cytisine. The 9-vinyl derivative was found to have a very similar agonist activity profile to that of cytisine.

  我们报告了几种胞嘧啶衍生物的合成和药理特性。其中，两个 10 取代的衍生物在结合检测中对 alpha4beta2 nAChR 亚型显示出比胞嘧啶高得多的选择性。发现 9-乙烯基衍生物具有与胞嘧啶非常相似的激动剂活性谱。
• The 3,7-diazabicyclo[3.3.1]nonane scaffold for subtype selective nicotinic acetylcholine receptor ligands. Part 2: Carboxamide derivatives with different spacer motifs
  作者：Christoph Eibl、Lenka Munoz、Isabelle Tomassoli、Clare Stokes、Roger L. Papke、Daniela Gündisch

  DOI：10.1016/j.bmc.2013.09.060

  日期：2013.12

  3,7-Diazabicyclo[3.3.1]nonane (bispidine) based nicotinic acetylcholine receptor (nAChR) ligands have been synthesized and evaluated for nAChRs interaction. Diverse spacer motifs were incorporated between the hydrogen bond acceptor (HBA) part and a variety of substituted (hetero)aryl moieties. Bispidine carboxamides bearing spacer motifs often showed high affinity in the low nanomolar range and selectivity for the alpha 4 beta 2* nAChR. Compounds 15, 25, and 47 with K-i values of about 1 nM displayed the highest affinities for alpha 4 beta 2* nAChR. All evaluated compounds are partial agonists or antagonists at alpha 4 beta 2*, with reduced or no effects on alpha 3 beta 4* with the exception of compound 15 (agonist), and reduced or no effect at alpha 7 and muscle subtypes. (C) 2013 Elsevier Ltd. All rights reserved.