3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester | 216853-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester
• 英文别名: Tert-butyl 3-pyridin-3-yl-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate
• CAS: 216853-20-2
• 化学式: C₁₇H₂₂N₂O₂
• 分子量: 286.374
• InChiKey: WRRVIWDMZZRXRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  42.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 以31%的产率得到3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  Novel Potent Ligands for the Central Nicotinic Acetylcholine Receptor:  Synthesis, Receptor Binding, and 3D-QSAR Analysis

  摘要：

  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.

  DOI：

  10.1021/jm990973d
• 作为产物：
  描述：

  N-苄基托品酮 在 5percent Pd/C 盐酸 、 正丁基锂 、 氯化亚砜 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 为溶剂， -70.0~50.0 ℃ 、101.33 kPa 条件下， 反应 21.67h， 生成 3-Pyridin-3-yl-8-aza-bicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Novel Potent Ligands for the Central Nicotinic Acetylcholine Receptor:  Synthesis, Receptor Binding, and 3D-QSAR Analysis

  摘要：

  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.

  DOI：

  10.1021/jm990973d

文献信息

• 8-Azabicyclo(3,2,1)oct-2 ene and octane derivatives as cholinergic ligands at nicotinic ACh receptors
  申请人：NeuroSearch A/S

  公开号：US20040019207A1

  公开（公告）日：2004-01-29

  The present invention discloses compounds of formula (1) any of its enantiomers or any mixture thereof, or a pharmaceutically acceptable salt thereof; wherein is a single or a double bond; R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or aralkyl; and R 1 is (a), wherein R 2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, amino; or aryl which may be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, thioalkoxy, thiocycloalkoxy, methylenedioxy, aryloxy, halogen, CF 3 , OCF 3 , CN, amino, aminoacyl, nitro, aryl and a monocyclic 5 to 6-membered heteroaryl group; a monocyclic 5 to 6-membered heteroaryl group which may be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl, cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, thioalkoxy, thiocycloalkoxy, methylenedioxy, aryloxy, halogen, CF 3 , OCF 3 , CN, amino, nitro, aryl and a monocyclic 5 to 6-membred lieteroaryl group; or a bicyclic heteroaryl group composed of a monocyclic 5 to 6 membered heteroaryl group fused to a benzene ring or fused to another monocyclic 5 to 6-membered heteroaryl, all of which may be substituted one or more times with substituents selected from the group consisting of alkyl, cycloalkyl cycloalkylalkyl alkenyl, alkynyl, alkoxy, cycloalkoxy, thioalkoxy, thiocycloalkoxy methylenedioxy, aryloxy, halogen, CF 3 , OCF 3 , CN, amino, nitro, aryl and a monocyclic 5 to 6-membered heteroaryl group. The compounds of the invention are useful as nicotinic ACh receptor ligands. 1

  本发明公开了式(1)化合物的任何对映体或其任何混合物，或其药学上可接受的盐； 其中 是单键或双键；R 是氢、烷基、烯基、炔基、环烷基、环烷基烷基、芳基或芳烷基；以及 R 1 是 (a)，其中 R 2 是氢、烷基、烯基、炔基、环烷基、环烷烃基、氨基；或芳基，可被选自以下组别的取代基一次或多次取代：烷基、环烷基、环烷烃基、烯基、炔基、烷氧基、环烷氧基、硫代烷氧基、硫代环烷氧基、亚甲基二氧基、芳氧基、卤素、CF 3 、OCF 3 烷基、环烷基、环烷基烯基、炔基、烷氧基、环烷氧基、硫代烷氧基、硫代环烷氧基、亚甲基二氧基、芳氧基、卤素、CF 3、OCF 3、CN、氨基、氨基酰基、硝基、芳基和单环 5 至 6 元杂芳基；单环 5 至 6 元杂芳基，可被选自以下组别的取代基一次或多次取代：烷基、环烷基、环烷基烯基、炔基、烷氧基、环烷氧基、硫代烷氧基、亚甲基二氧基、芳氧基、卤素、CF 3、OCF 3、CN、氨基、氨基酰基、硝基、芳基和单环 5 至 6 元杂芳基。 3 、OCF 3 、CN、氨基、硝基、芳基和单环 5 至 6 嵌段杂芳基；或双环杂芳基，由与苯环融合的单环 5-6 位杂芳基或与另一个单环 5-6 位杂芳基融合的单环 5-6 位杂芳基组成，所有这些杂芳基可被选自以下组别的取代基一次或多次取代：烷基、环烷基环烷基烯基、炔基、烷氧基、环烷氧基、硫代烷氧基、硫代环烷氧基亚甲基二氧基、芳氧基、卤素、CF 3 OCF 3 、CN、氨基、硝基、芳基和单环 5 至 6 元杂芳基。本发明的化合物可用作烟碱 ACh 受体配体。 1
• 8-AZABICYCLO(3,2,1)OCT-2-ENE AND OCTANE DERIVATIVES AS CHOLINERGIC LIGANDS AT NICOTINIC ACH RECEPTORS
  申请人：NEUROSEARCH A/S

  公开号：EP0984965A1

  公开（公告）日：2000-03-15
• US6645977B1
  申请人：——

  公开号：US6645977B1

  公开（公告）日：2003-11-11
• US6897231B2
  申请人：——

  公开号：US6897231B2

  公开（公告）日：2005-05-24
• US6964972B2
  申请人：——

  公开号：US6964972B2

  公开（公告）日：2005-11-15