5-[(1R,5S)-3,6-diazabicyclo[3.2.0]hept-6-yl]nicotinonitrile | 370882-41-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-[(1R,5S)-3,6-diazabicyclo[3.2.0]hept-6-yl]nicotinonitrile
• 英文别名: 3-Pyridinecarbonitrile, 5-(1R,5S)-3,6-diazabicyclo(3.2.0)hept-6-yl-；5-[(1R,5S)-3,6-diazabicyclo[3.2.0]heptan-6-yl]pyridine-3-carbonitrile
• CAS: 370882-41-0
• 化学式: C₁₁H₁₂N₄
• 分子量: 200.243
• InChiKey: GPXAWLDGWSBLKM-MWLCHTKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  52
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (S,s)-3-cbz-3,6-二氮杂双环环[3.2.0]庚烷 在 tris(dibenzylideneacetone)dipalladium (0) caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 作用下， 以 甲苯 、 三氟乙酸 为溶剂， 反应 41.0h， 生成 5-[(1R,5S)-3,6-diazabicyclo[3.2.0]hept-6-yl]nicotinonitrile
  参考文献：
  名称：

  A-366833: A novel nicotinonitrile-substituted 3,6-diazabicyclo[3.2.0]-heptane α4β2 nicotinic acetylcholine receptor selective agonist: Synthesis, analgesic efficacy and tolerability profile in animal models

  摘要：

  5-[(1R,5S)-3,6-Diazabicyclo[3.2.0]heptan-6-yl]nicotinonitrile (A-366833) is a novel nicotinic acetylcholine receptor (nAChR) ligand that binds to the agonist-binding site ([H-3]-cytisine) with K-i value of 3.1 nM and exhibits agonist selectivity at alpha 4 beta 2 nAChR relative to the alpha 3 beta 4 nAChR subtype. The analgesic effects of A-366833 were examined across a variety of animal models including the mouse model of writhing pain (abdominal constriction), the rat models of acute thermal (hot box), persistent chemical (formalin) and neuropathic (spinal nerve ligation, SNL) pain. In the abdominal constriction model, A-366833 was effective at doses ranging from 0.062 to 0.62 mu mol/kg (i.p.). In addition, A-366833 demonstrated significant effects in acute thermal pain (6.2-19.0 mu mol/kg, i.p.), formalin (1.9-19 mu mol/kg i.p.) and SNL (1.9-19 mu mol/kg i.p.) models. The systemic effects of A-366833 were attenuated by pretreatment with mecamylamine (5 mu mol/kg i.p.) in both the formalin and SNL models, suggesting that the analgesic effects of A-366833 in models of persistent nociceptive and neuropathic pain are mediated by activation of nAChRs. Pharmacokinetic investigations of A-366833 in rat revealed moderate brain:plasma distribution, half-life of 1.5 h and excellent oral bioavailability of 73%. Comparison of peak plasma levels at the minimal effective doses across rat models of acute thermal pain, formalin and SNL with the maximal exposure that does not evoke emesis in ferret revealed therapeutic margins ranging from 6- to 22-fold. These studies indicate that compounds like A-366833 with improved agonist selectivity at alpha 4 beta 2 vs. alpha 3 beta 4 nAChR can elicit a broad spectrum of analgesic efficacy without concurrent adverse effects. (C) 2007 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bcp.2007.08.010

文献信息

• Diazabicyclic central nervous system active agents
  申请人：——

  公开号：US20020019388A1

  公开（公告）日：2002-02-14

  Compounds of formula I 1 pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.

  式I1的化合物，这些化合物的药物组合物，以及利用这些组合物来控制哺乳动物的突触传递。
• Synthesis and Structure−Activity Relationship Studies of 3,6-Diazabicyclo[3.2.0]heptanes as Novel α4β2 Nicotinic Acetylcholine Receptor Selective Agonists
  作者：Jianguo Ji、Michael R. Schrimpf、Kevin B. Sippy、William H. Bunnelle、Tao Li、David J. Anderson、Connie Faltynek、Carol S. Surowy、Tino Dyhring、Philip K. Ahring、Michael D. Meyer

  DOI：10.1021/jm070755h

  日期：2007.11.1

  influences of the 3,6-diazabicyclo[3.2.0]heptane core. Small 5-substituents on the pyridine ring had a modest impact on the binding affinities and functional activities. 6-Bromo, 6-chloro, and 6-methyl substituents on the pyridine ring led to increased binding affinities and improved functional activities. Most of the 6-N-pyridinyl-substituted 3,6-diazabicyclo[3.2.0]heptanes are selective for the alpha4beta2

  合成了一系列从3,6-二氮杂双环[3.2.0]庚烷衍生的新型有效神经元烟碱乙酰胆碱受体（nAChR）配体，并评估了其对alpha4beta2 nAChR亚型的结合亲和力和激动剂活性。这些新型nAChR配体的结构活性关系研究集中于对吡啶环的取代作用以及3,6-二氮杂双环[3.2.0]庚烷核心的立体和区域化学影响。吡啶环上的5个小取代基对结合亲和力和功能活性影响不大。吡啶环上的6-溴，6-氯和6-甲基取代基导致增加的结合亲和力和改善的功能活性。大多数6-N-吡啶基取代的3,6-二氮杂双环[3.2.0]庚烷对alpha4beta2 nAChR亚型具有选择性。化合物（1R，5S）-25，（1R，5S）-55，和（1R，5S）-56在halpha3beta4 nAChR上几乎没有活性，但在halpha4beta2 nAChR亚型上保留了效力和功效。3-N-吡啶基取代的系列显示出更复杂的SAR。发现（
• DIAZABICYCLIC CENTRAL NERVOUS SYSTEM ACTIVE AGENTS
  申请人：Schrimpf R. Michael

  公开号：US20080097094A1

  公开（公告）日：2008-04-24

  Compounds of formula I pharmaceutical compositions of these compounds, and use of said compositions to control synaptic transmission in mammals.

  化合物I的配方药物组合物，以及使用该组合物来控制哺乳动物的突触传递。
• Novel starch derivatives and a method for their preparation
  申请人：Peltonen Soili

  公开号：US20050107603A1

  公开（公告）日：2005-05-19

  The invention relates to novel transglycosylation products and their preparation. The transglycosylation products according to the invention are prepared from starch derivatives, such as esters or ethers of starch. The products are obtained by reacting a starch derivative with an alcohol in the presence of an acid catalyst. The forming product is separated by precipitation or by removing any unreacted alcohol by evaporation. In the products according to the invention the good properties of starch derivatives, such as the excellent water resistance of esters, are combined with the versatility of transglycoside products. The products can be used as adhesives, in which case they are formulated, for example as hot-melt adhesives, and as comonomers, prepolymers or macroinitiators in the preparation of polymers.

  本发明涉及新型转糖基化产物及其制备。根据本发明，转糖基化产物由淀粉衍生物，如淀粉的酯或醚制备而成。在酸催化剂的作用下，淀粉衍生物与醇类发生反应，从而得到转糖基化产物。形成的产品通过沉淀或蒸发去除未反应的醇而分离。在本发明的产品中，淀粉衍生物的优良特性（如酯类的优异耐水性）与转糖苷产品的多功能性相结合。这些产品可用作粘合剂，例如热熔粘合剂，也可用作制备聚合物的共聚单体、预聚物或大引发剂。
• NOVEL STARCH DERIVATIVES AND A METHOD FOR THEIR PREPARATION
  申请人：Valtion Teknillinen Tutkimuskeskus

  公开号：EP1474452A1

  公开（公告）日：2004-11-10