(1S)-2-(6-phenyl-3-pyridazinyl)-2,5-diazabicyclo[2.2.1]heptane

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: (1S)-2-(6-phenyl-3-pyridazinyl)-2,5-diazabicyclo[2.2.1]heptane
• 英文别名: (1S,4S)-2-(6-phenylpyridazin-3-yl)-2,5-diazabicyclo[2.2.1]heptane
• 化学式: C₁₅H₁₆N₄
• 分子量: 252.319
• InChiKey: UNNFMHIMJIHAMM-STQMWFEESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  41
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S)-2-(6-phenyl-3-pyridazinyl)-2,5-diazabicyclo[2.2.1]heptane 、 聚合甲醛 在 三乙酰氧基硼氢化钠 作用下， 以 乙腈 为溶剂， 反应 10.0h， 以90%的产率得到(1S,4S)-2-methyl-5-(6-phenylpyridazin-3-yl)-2,5-diazabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Syntheses and structure–activity relationship (SAR) studies of 2,5-diazabicyclo[2.2.1]heptanes as novel α7 neuronal nicotinic receptor (NNR) ligands

  摘要：

  Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha 7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha 7 NNR agonist activity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.105
• 作为产物：
  描述：

  (1S,4S)-tert-butyl 5-(6-chloropyridazin-3-yl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate 在 盐酸 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 水 、 乙腈 为溶剂， 反应 20.0h， 生成 (1S)-2-(6-phenyl-3-pyridazinyl)-2,5-diazabicyclo[2.2.1]heptane
  参考文献：
  名称：

  Structure–activity relationship studies of SEN12333 analogues: Determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs

  摘要：

  Alpha7 nicotinic acetylcholine receptors (nAChRs) have implications in the regulation of cognitive processes such as memory and attention and have been identified as a promising therapeutic target for the treatment of the cognitive deficits associated with schizophrenia and Alzheimer's disease (AD). Structure affinity relationship studies of the previously described alpha 7 agonist SEN12333 (8), have resulted in the identification of compound 45, a potent and selective agonist of the alpha 7 nAChR with enhanced affinity and improved physicochemical properties over the parent compound (SEN12333, 8). (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.025

文献信息

• 2,5,-diazabicyclo[2.2.1]heptane derivatives, their preparation and therapeutic uses
  申请人：Sanofi-Synthelabo

  公开号：US06635645B1

  公开（公告）日：2003-10-21

  The invention relates to 2,5-diazabicyclo[2.2.1]heptane derivatives, to pharmaceutical compositions containing them, and to methods for the treatment or prevention of disorders associated with a dysfunction of the nicotinic receptors utilizing them.

  这项发明涉及2,5-二氮杂双环[2.2.1]庚烷衍生物，含有它们的药物组合物，以及利用它们治疗或预防与尼古丁受体功能障碍相关的疾病的方法。
• Syntheses and structure–activity relationship (SAR) studies of 2,5-diazabicyclo[2.2.1]heptanes as novel α7 neuronal nicotinic receptor (NNR) ligands
  作者：Tao Li、William H. Bunnelle、Keith B. Ryther、David J. Anderson、John Malysz、Rosalind Helfrich、Jens H. Grønlien、Monika Håkerud、Dan Peters、Michael R. Schrimpf、Murali Gopalakrishnan、Jianguo Ji

  DOI：10.1016/j.bmcl.2010.04.105

  日期：2010.6

  Biaryl substituted 2,5-diazabicyclo[2.2.1]heptanes have been synthesized and tested for their affinity toward alpha 7 neuronal nicotinic receptors (NNRs). SAR studies established that 5-N-methyl substituent, heteroaryl linker and the nature of terminal aryl group are critical for the ligand to achieve potent alpha 7 NNR agonist activity. (C) 2010 Elsevier Ltd. All rights reserved.
• Structure–activity relationship studies of SEN12333 analogues: Determination of the optimal requirements for binding affinities at α7 nAChRs through incorporation of known structural motifs
  作者：Corinne Beinat、Tristan Reekie、Samuel D. Banister、James O'Brien-Brown、Teresa Xie、Thao T. Olson、Yingxian Xiao、Andrew Harvey、Susan O'Connor、Carolyn Coles、Anton Grishin、Peter Kolesik、John Tsanaktsidis、Michael Kassiou

  DOI：10.1016/j.ejmech.2015.03.025

  日期：2015.5

  Alpha7 nicotinic acetylcholine receptors (nAChRs) have implications in the regulation of cognitive processes such as memory and attention and have been identified as a promising therapeutic target for the treatment of the cognitive deficits associated with schizophrenia and Alzheimer's disease (AD). Structure affinity relationship studies of the previously described alpha 7 agonist SEN12333 (8), have resulted in the identification of compound 45, a potent and selective agonist of the alpha 7 nAChR with enhanced affinity and improved physicochemical properties over the parent compound (SEN12333, 8). (C) 2015 Elsevier Masson SAS. All rights reserved.