3-(3,4-dichloro-phenyl)-8-aza-bicyclo[3.2.1]oct-2-ene | 912641-16-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(3,4-dichloro-phenyl)-8-aza-bicyclo[3.2.1]oct-2-ene
• 英文别名: 3-(3,4-dichlorophenyl)-2-nortropene；(+/-)-3-(3,4-Dichlorophenyl)-8-azabicyclo[3.2.1]oct-2-ene；3-(3,4-Dichlorophenyl)-8-azabicyclo[3.2.1]oct-2-ene
• CAS: 912641-16-8；912641-29-3；189746-56-3
• 化学式: C₁₃H₁₃Cl₂N
• 分子量: 254.159
• InChiKey: WNTMTTVEDFGEMS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(3,4-dichloro-phenyl)-8-aza-bicyclo[3.2.1]oct-2-ene 、 4-(3-chloropropoxy)-1H-indole 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 生成 4-{3-[3-(3,4-Dichloro-phenyl)-8-aza-bicyclo[3.2.1]oct-2-en-8-yl]-propoxy}-1H-indole
  参考文献：
  名称：

  Novel aryloxy-8-azabicyclo[3.2.1]oct-3-enes with 5-HT transporter and 5-HT1A affinity

  摘要：

  Joining aryl 8-azabicyclo[3.2.1]oct-3-enes with aryloxyethanes and aryloxypropanes produces novel series of compounds 11 and 12 with potent 5-HT-T affinity and moderately potent 5-HT1A affinity. Moreover, several of these compounds possess functional 5-HT1A antagonism. Optimal compounds are, 4-indolyloxyethane 21, 4-indolyloxypropanes 25, and 27, which possess potent 5-HT-T affinity (5-HT-T K-i: 21: 1.2 nM, 25: 0.54 nM, 27: 0.38 nM) and good 5-HT1A affinity/antagonism (5-HT1A K-i, [S-35]GTPgammaS: E-max (%): 21: 111.1 nM, 0% 25: 173.2 nM, 0%; 27: 107 nM, 0%). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.030
• 作为产物：
  描述：

  托品酮 在 sodium hydroxide 、 1-氯乙基氯甲酸酯 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 1,2-二氯乙烷 、 异丙醇 为溶剂， 生成 3-(3,4-dichloro-phenyl)-8-aza-bicyclo[3.2.1]oct-2-ene
  参考文献：
  名称：

  Novel aryloxy-8-azabicyclo[3.2.1]oct-3-enes with 5-HT transporter and 5-HT1A affinity

  摘要：

  Joining aryl 8-azabicyclo[3.2.1]oct-3-enes with aryloxyethanes and aryloxypropanes produces novel series of compounds 11 and 12 with potent 5-HT-T affinity and moderately potent 5-HT1A affinity. Moreover, several of these compounds possess functional 5-HT1A antagonism. Optimal compounds are, 4-indolyloxyethane 21, 4-indolyloxypropanes 25, and 27, which possess potent 5-HT-T affinity (5-HT-T K-i: 21: 1.2 nM, 25: 0.54 nM, 27: 0.38 nM) and good 5-HT1A affinity/antagonism (5-HT1A K-i, [S-35]GTPgammaS: E-max (%): 21: 111.1 nM, 0% 25: 173.2 nM, 0%; 27: 107 nM, 0%). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.08.030

文献信息

• Aryl-8-azabicyclo [3.2.1] octanes for the treatment of depression
  申请人：Wyeth

  公开号：US20030032645A1

  公开（公告）日：2003-02-13

  The present invention includes compounds of formula I 1 wherein A, X, n, Ar 1 , and Ar 2 are defined as set forth herein. These compounds may be used to treat depression. The invention also includes formulations containing these compounds, and methods for making and using compounds of this invention.

  本发明包括式I1的化合物，其中A、X、n、Ar1和Ar2如本文所述。这些化合物可用于治疗抑郁症。本发明还包括含有这些化合物的配方，以及制备和使用本发明化合物的方法。
• [EN] 8-AZABICYCLO[3.2.1]OCT-2-ENE DERIVATIVES, THEIR PREPARATION AND USE<br/>[FR] DERIVES DE 8-AZABICYCLO(3.2.1)OCT-2-ENE, LEUR PREPARATION ET LEUR UTILISATION
  申请人：NEUROSEARCH A/S

  公开号：WO1997013770A1

  公开（公告）日：1997-04-17

  (EN) A compound having formula (I) or any of its enantiomers of any mixture thereof, or a pharmaceutically acceptable salt thereof; wherein R is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl or 2-hydroxyethyl; and R4 is phenyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl and aryl; 3,4-methylenedioxyphenyl; benzyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl and aryl; heteroaryl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl and aryl; or naphtyl which may be substituted one or more times with substituents selected from the group consisting of halogen, CF3, CN, alkoxy, cycloalkoxy, alkyl, cycloalkyl, alkenyl, alkynyl, amino, nitro, heteroaryl and aryl. The compounds possess valuable pharmaceutical properties as monoamine neurotransmitter re-uptake inhibitors.(FR) Cette invention concerne un composé de formule (I) où R représente hydrogène, alkyle, alcényle, alcynyle, cycloalkyle, cycloalkylalkyle ou 2-hydroxyéthyle, et R4 représente les éléments suivants: phényle pouvant être substitué une ou plusieurs fois par des substituants choisis dans le groupe comprenant halogène, CF3, CN, alcoxy, cycloalcoxy, alkyle, cycloalkyle, alcényle, alcynyle, amino, nitro, hétéroaryle et aryle; 3,4-méthylènedioxyphényle; benzyle pouvant être substitué une ou plusieurs fois par des substituants choisis dans le groupe comprenant halogène, CF3, CN, alcoxy, cycloalcoxy, alkyle, cycloalkyle, alcényle, alcynyle, amino, nitro, hétéroaryle et aryle; hétéroaryle pouvant être substitué une ou plusieurs fois par des substituants choisis dans le groupe comprenant halogène, CF3, CN, alcoxy, cycloalcoxy, alkyle, cycloalkyle, alcényle, alcynyle, amino, nitro, hétéroaryle et aryle; ou encore naphthyle pouvant être substitué une ou plusieurs fois par des substituants choisis dans le groupe comprenant halogène, CF3, CN, alcoxy, cycloalcoxy, alkyle, cycloalkyle, alcényle, alcynyle, amino, nitro, hétéroaryle et aryle. Cette invention concerne également les énantiomères quels qu'ils soient de ces composés, tout mélange de ces derniers, ainsi que leurs sels acceptables sur le plan pharmaceutique. Ces composés possèdent de très bonnes propriétés pharmaceutiques en qualité d'inhibiteurs de réabsorption de neurotransmetteur de monoamine.

  一种具有化学式（I）或其任何对映体或其混合物的药物可接受的盐的化合物；其中R为氢、烷基、烯基、炔基、环烷基、环烷基烷基或2-羟乙基；R4为苯基，其可以被取代一次或多次，所述取代基选自卤素、CF3、CN、烷氧基、环烷氧基、烷基、环烷基、烯基、炔基、氨基、硝基、杂环芳基和芳基的群；3,4-亚甲二氧基苯基；苄基，其可以被取代一次或多次，所述取代基选自卤素、CF3、CN、烷氧基、环烷氧基、烷基、环烷基、烯基、炔基、氨基、硝基、杂环芳基和芳基的群；杂环芳基，其可以被取代一次或多次，所述取代基选自卤素、CF3、CN、烷氧基、环烷氧基、烷基、环烷基、烯基、炔基、氨基、硝基、杂环芳基和芳基的群；或萘基，其可以被取代一次或多次，所述取代基选自卤素、CF3、CN、烷氧基、环烷氧基、烷基、环烷基、烯基、炔基、氨基、硝基、杂环芳基和芳基的群。这些化合物作为单胺神经递质再摄取抑制剂具有有价值的药物性质。
• Aryl-8-azabicyclo&lsqb;3.2.1&rsqb;octanes for the treatment of depression
  申请人：Wyeth

  公开号：US06632824B2

  公开（公告）日：2003-10-14

  The present invention includes compounds of formula I wherein A, X, n, Ar1, and Ar2 are defined as set forth herein. These compounds may be used to treat depression. The invention also includes formulations containing these compounds, and methods for making and using compounds of this invention.

  本发明涉及公式I的化合物，其中A、X、n、Ar1和Ar2的定义如本文所述。这些化合物可用于治疗抑郁症。本发明还包括含有这些化合物的配方以及制备和使用本发明中化合物的方法。
• Modulation of selective serotonin reuptake inhibitor and 5-HT1A antagonist activity in 8-aza-bicyclo[3.2.1]octane derivatives of 2,3-dihydro-1,4-benzodioxane
  作者：Adam M. Gilbert、Gary P. Stack、Ramaswamy Nilakantan、Jason Kodah、Megan Tran、Rosemary Scerni、Xiaojie Shi、Deborah L. Smith、Terrance H. Andree

  DOI：10.1016/j.bmcl.2003.10.024

  日期：2004.1

  2,3-Dihydro-1,4-benzodioxanes with aryl 8-aza-bicyclo[3.2.1]oct-3-ene attachments 2 produce compounds with potent 5-HT-T affinity, and weak 5-HT1A affinity and a, affinity. This compares with 2,3-dihydro-1,4-benzodioxanes containing 8-aza-bicyclo[3.2.1] octan-3-ol attachments 4 which possess potent 5-HT1A affinity, moderate to good selectivity over a, and little 5-HT-T affinity. A 3-benzothiophene analogue of 4 (30) was synthesized which possesses potent 5-HT1A affinity and especially good selectivity over both a, and 5-HT-T. (C) 2003 Elsevier Ltd. All rights reserved.
• Synthesis and monoamine transporter affinity of 3α-arylmethoxy-3β-arylnortropanes
  作者：Harneet Kaur、Sari Izenwasser、Abha Verma、Dean Wade、Amy Housman、Edwin D. Stevens、David L. Mobley、Mark L. Trudell

  DOI：10.1016/j.bmcl.2009.10.087

  日期：2009.12

  A series of 3-arylnortrop-2-enes and 3 alpha-arylmethoxy-3 beta-arylnortropanes were synthesized and evaluated for binding affinity at monoamine transporters. The 3-(3,4-dichlorophenyl)nortrop-2-ene (6e) exhibited high affinity for the SERT (K-i = 0.3 nM). The 3 alpha-arylmethoxy-3 beta-arylnortropanes were generally SERT selective with the 3 alpha-(3,4-dichlorophenylmethoxy)-3 beta phenylnortrop-2-ene (7c) possessing subnanomolar potency (K-i = 0.061 nM). However, 3 alpha-(3,4-dichlorophenylmethoxy)-3 beta-phenylnortrop-2-ene (7b) exhibited high affinity at all three transporters [(DAT K-i = 22 nM), (SERT K-i = 6 nM) and (NET K-i = 101 nM)]. (C) 2009 Elsevier Ltd. All rights reserved.