3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene | 216853-22-4

• 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: 3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene
• 英文别名: 3-(Pyridin-3-yl)-8-azabicyclo[3.2.1]oct-3-ene；3-pyridin-3-yl-8-azabicyclo[3.2.1]oct-2-ene
• CAS: 216853-22-4
• 化学式: C₁₂H₁₄N₂
• 分子量: 186.257
• InChiKey: OWYJMZSLCXNXPU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  24.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [11C]methyl iodide 、 3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene 生成 8-(111C)methyl-3-pyridin-3-yl-8-azabicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  Drandarov, K.; Mu, L. J.; Bisson, W., Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S180 - S180

  摘要：

  DOI：
• 作为产物：
  描述：

  二乙基(3-吡啶基)-硼烷 在 bis-triphenylphosphine-palladium(II) chloride 、 碘代三甲硅烷 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 3.5h， 生成 3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  3D QSAR Analyses-Guided Rational Design of Novel Ligands for the (α4)₂(β2)₃ Nicotinic Acetylcholine Receptor

  摘要：

  Three-dimensional quantitative structure-activity relationship methods, the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), were applied using a training set of 45 ligands of the (alpha4)(2)(beta2)(3) nicotinic acetylcholine receptor (nAChR). All compounds are related to (-)-epibatidine, (-)-cytisine, (+)-anatoxin-a, and (-)-ferruginine, and additionally, novel diazabicyclo[4.2.1]nonane- and quinuclidin-2-ene-based structures were included. Their biological data have been determined by utilizing the same experimental protocol. Statistically reliable models of good predictive power (CoMFA r(2) = 0.928, q(2) = 0.692, no. of components = 3; CoMSIA r(2) = 0.899, q(2) = 0.701, no. of components = 3) were achieved. The results obtained were graphically interpreted in terms of field contribution maps. Hence, physicochemical. determinants of binding, such as steric and electrostatic and, for the first time, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties, were mapped back onto the molecular structures of a set of nAChR modulators. In particular, changes in the binding affinity of the modulators as a result of modifications in the aromatic ring systems could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. These results were used to guide the rational design of new nAChR ligands such as 48-52 and 54, which were subsequently synthesized for the first time and tested. Key steps of our synthetic approaches were successfully applied Stille and Suzuki cross-coupling reactions. Predictive r(2) values of 0.614 and 0.660 for CoMFA and CoMSIA, respectively, obtained for 22 in part previously unknown ligands for the (alpha4)(2)(beta2)(3) subtype, demonstrate the high quality of the 3D QSAR models.

  DOI：

  10.1021/jm020859m

文献信息

• Novel Potent Ligands for the Central Nicotinic Acetylcholine Receptor:  Synthesis, Receptor Binding, and 3D-QSAR Analysis
  作者：Simon Feldbæk Nielsen、Elsebet Østergaard Nielsen、Gunnar M. Olsen、Tommy Liljefors、Dan Peters

  DOI：10.1021/jm990973d

  日期：2000.6.1

  In the past few years the focus on central acetylcholine receptors has shifted from compounds with affinity for muscarinic acetylcholine receptors (mAChR) to compounds with affinity for nicotinic acetylcholine receptors (nAChR). The therapeutic potential includes treatment of a variety of diseases, e.g., Alzheimer's disease, Parkinson's disease, and Tourette's syndrome. This work describes the synthesis of six novel series of potent ligands with nanomolar affinity for the alpha 4 beta 2 nAChR subtype. Structure-activity relationship (SAR) was evaluated by the calculation of a 3D-QSAR model. 3D-QSAR analysis of the compounds using the GRID/GOLPE methodology resulted in a model of high quality (R-2 = 0.97, Q(2) = 0.81). The coefficient plots reveal that the steric interactions between the target and our compounds are of major importance for the affinity. Bulky substituents in the B-position of the pyridine ring will reduce the affinity of the compounds, whereas bulky ring systems including a sp(3)-nitrogen will increase the affinity of the compounds.
• 3D QSAR Analyses-Guided Rational Design of Novel Ligands for the (α4)₂(β2)₃ Nicotinic Acetylcholine Receptor
  作者：Holger Gohlke、Simone Schwarz、Daniela Gündisch、Maria Cristina Tilotta、Alexander Weber、Thomas Wegge、Gunther Seitz

  DOI：10.1021/jm020859m

  日期：2003.5.1

  Three-dimensional quantitative structure-activity relationship methods, the comparative molecular field analysis (CoMFA) and the comparative molecular similarity indices analysis (CoMSIA), were applied using a training set of 45 ligands of the (alpha4)(2)(beta2)(3) nicotinic acetylcholine receptor (nAChR). All compounds are related to (-)-epibatidine, (-)-cytisine, (+)-anatoxin-a, and (-)-ferruginine, and additionally, novel diazabicyclo[4.2.1]nonane- and quinuclidin-2-ene-based structures were included. Their biological data have been determined by utilizing the same experimental protocol. Statistically reliable models of good predictive power (CoMFA r(2) = 0.928, q(2) = 0.692, no. of components = 3; CoMSIA r(2) = 0.899, q(2) = 0.701, no. of components = 3) were achieved. The results obtained were graphically interpreted in terms of field contribution maps. Hence, physicochemical. determinants of binding, such as steric and electrostatic and, for the first time, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties, were mapped back onto the molecular structures of a set of nAChR modulators. In particular, changes in the binding affinity of the modulators as a result of modifications in the aromatic ring systems could be rationalized by the steric, electrostatic, hydrophobic, and hydrogen bond acceptor properties. These results were used to guide the rational design of new nAChR ligands such as 48-52 and 54, which were subsequently synthesized for the first time and tested. Key steps of our synthetic approaches were successfully applied Stille and Suzuki cross-coupling reactions. Predictive r(2) values of 0.614 and 0.660 for CoMFA and CoMSIA, respectively, obtained for 22 in part previously unknown ligands for the (alpha4)(2)(beta2)(3) subtype, demonstrate the high quality of the 3D QSAR models.
• Drandarov, K.; Mu, L. J.; Bisson, W., Journal of labelled compounds and radiopharmaceuticals, 2003, vol. 46, p. S180 - S180
  作者：Drandarov, K.、Mu, L. J.、Bisson, W.、Kessler, L.、Schubiger, P. A.、Westera, G.

  DOI：——

  日期：——