(+/-)-3-(3-Pyridyl)-9-tert-butoxycarbonyl-9-azabicyclo[3.3.1]non-2-ene | 216581-20-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (+/-)-3-(3-Pyridyl)-9-tert-butoxycarbonyl-9-azabicyclo[3.3.1]non-2-ene
• 英文别名: Tert-butyl 3-pyridin-3-yl-9-azabicyclo[3.3.1]non-2-ene-9-carboxylate
• CAS: 216581-20-3
• 化学式: C₁₈H₂₄N₂O₂
• 分子量: 300.401
• InChiKey: IFFUYKRTOSSFLH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 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-(3-Pyridyl)-9-tert-butoxycarbonyl-9-azabicyclo[3.3.1]non-2-ene 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 3-(Pyridin-3-yl)-9-azabicyclo[3.3.1]non-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：

  9-苄基-9-氮杂双环[3.3.1]壬烷-3-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-(3-Pyridyl)-9-tert-butoxycarbonyl-9-azabicyclo[3.3.1]non-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

文献信息

• 9-azobicyclo[3.3.1] non-2-ene derivatives as cholinergic ligands at nicotinic ACH receptors
  申请人：NeuroSearch A/S

  公开号：US06392045B1

  公开（公告）日：2002-05-21

  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 R1 is (a), wherein R2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, amino; 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, CF3, OCF3, 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, CF3, OCF3, CN, amino, nitro, aryl and a monocyclic 5 to 6-membered heteroaryl 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, CF3, OCF3, 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.

  本发明揭示了化合物的结构如下（1），其任一对映异构体或其混合物，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，芳基或芳基烷基；R1是（a），其中R2是氢，烷基，烯基，炔基，环烷基，环烷基烷基，氨基；芳基，可能一次或多次被来自由烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、硫代烷氧基、硫代环烷氧基、亚甲二氧基、芳氧基、卤素、CF3、O 、CN、氨基、氨基酰基、硝基、芳基和单环5到6成员杂芳基组成的取代基所取代；一次或多次被来自烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、硫代烷氧基、硫代环烷氧基、亚甲二氧基、芳氧基、卤素、 、O 、CN、氨基、硝基、芳基和单环5到6成员杂芳基组成的取代基所取代的一次或多次的单环5到6成员杂芳基；或由一个单环5到6成员杂芳基与苯环或另一个单环5到6成员杂芳基融合而成的双环杂芳基，所有这些可能被来自烷基、环烷基、环烷基烷基、烯基、炔基、烷氧基、环烷氧基、硫代烷氧基、硫代环烷氧基、亚甲二氧基、芳氧基、卤素、 、O 、CN、氨基、硝基、芳基和单环5到6成员杂芳基组成的取代基所取代。本发明的化合物可用作尼古丁ACh受体配体。
• 9-AZABICYCLO(3.3.1)NON-2-ENE AND NONANE DERIVATIVES AS CHOLINERGIC LIGANDS AT NICOTINIC ACh RECEPTORS
  申请人：NEUROSEARCH A/S

  公开号：EP0984966B1

  公开（公告）日：2003-01-29
• US6392045B1
  申请人：——

  公开号：US6392045B1

  公开（公告）日：2002-05-21
• [EN] 9-AZABICYCLO(3.3.1)NON-2-ENE AND NONANE DERIVATIVES AS CHOLINERGIC LIGANDS AT NICOTINIC ACh RECEPTORS<br/>[FR] DERIVES DE 9-AZABICYCLO(3.3.1)NON-2-ENE ET NONANE UTILISES COMME LIGANDS CHOLINERGIQUES DE RECEPTEURS NICOTINIQUES DE L'ACH.
  申请人：NEUROSEARCH A/S

  公开号：WO1998054182A1

  公开（公告）日：1998-12-03

  (EN) 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 R1 is (a), wherein R2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, amino; 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, CF3, OCF3, 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, CF3, OCF3, CN, amino, nitro, aryl and a monocyclic 5 to 6-membered heteroaryl 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, CF3, OCF3, 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.(FR) La présente invention concerne des composés de la formule (1), n'importe lequel de leurs énantiomères ou n'importe quel mélange de ceux-ci, ou leur sel acceptable sur le plan pharmaceutique, formule dans laquelle - - - - représente une liaison simple ou une liaison double; R représente hydrogène, alkyle, alcényle, alkynyle, cycloalkyle, cycloalkylalkyle, aryle ou aralkyle; et R1 a la formule (a) dans laquelle R2 représente hydrogène, alkyle, alcényle, alkynyle, cycloalkyle, cycloalkylalkyle, amino; ou aryle pouvant être substitué une ou plusieurs fois par des substituents choisis dans le groupe comprenant alkyle, cycloalkyle, cycloalkylalkyle alcényle, alkynyle, alcoxy, cycloalcoxy, thioalcoxy, thiocycloalcoxy, méthylènedioxy, aryloxy, halogène, CF3, OCF3, CN, amino, aminoacyle, nitro, aryle ainsi qu'un groupe hétéroaryle monocyclique constitué de 5 à 6 éléments; un groupe hétéroaryle monocyclique constitué de 5 à 6 éléments, pouvant être substitué une ou plusieurs fois par des substituents choisis dans le groupe comprenant alkyle, cycloalkyle, cycloalkylalkyle alcényle, alkynyle, alcoxy, cycloalcoxy, thioalcoxy, thiocycloalcoxy, méthylènedioxy, aryloxy, halogène, CF3, OCF3, CN, amino, nitro, aryle ainsi qu'un groupe hétéroaryle monocyclique constitué de 5 à 6 éléments; ou un groupe hétéroaryle bicyclique composé d'un groupe hétéroaryle monocyclique constitué de 5 à 6 éléments fusionné à un cycle benzène ou fusioné à un autre hétéroaryle monocyclique constitué de 5 à 6 éléments, et lequel peut être substitué une ou plusieurs fois par des substituents choisis dans le groupe comprenant alkyle, cycloalkyle, cycloalkylalkyle alcényle, alkynyle, alcoxy, cycloalcoxy, thioalcoxy, thiocycloalcoxy, méthylènedioxy, aryloxy, halogène, CF3, OCF3, CN, amino, nitro, aryle ainsi qu'un groupe hétéroaryle monocyclique constitué de 5 à 6 éléments. Les composés de l'invention sont utiles en tant que ligands de récepteurs nicotiniques de l'ACh.