(1R,5S/1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane

• 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: (1R,5S/1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane
• 英文别名: (1S,5R/1R,5S)-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane；(1R,5S)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane
• 化学式: C₁₂H₁₁F₄N
• 分子量: 245.22
• InChiKey: ZCHPFSLSIJTHFX-LDYMZIIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,5S/1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane 在 左旋樟脑磺酸 、 sodium hydroxide 、 水 作用下， 以 乙腈 、 二氯甲烷 为溶剂， 反应 1.08h， 生成 (1S,5R)-1-[2-fluoro-4-(trifluoromethyl)pheny|]-3-azabicyclo-[3.1.0]hexane
  参考文献：
  名称：

  WO2006/136223

  摘要：

  公开号：
• 作为产物：
  描述：

  2-氟-4-(三氟甲基)苯胺 在 亚硝酸特丁酯 、 硼烷四氢呋喃络合物 、 sodium hydride 、 copper dichloride 作用下， 以 四氢呋喃 、 二甲基亚砜 、 乙腈 为溶剂， 反应 25.5h， 生成 (1R,5S/1S,5R)-1-[2-fluoro-4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane
  参考文献：
  名称：

  WO2006/136223

  摘要：

  公开号：

文献信息

• [EN] AZABICYCLO (3.1.0) HEXANE DERIVATIVES USEFUL AS MODULATORS OF DOPAMINE D3 RECEPTORS<br/>[FR] DERIVES AZABICYCLO (3.1.0) HEXANE UTILES COMME MODULATEURS DES RECEPTEURS D3 DE LA DOPAMINE
  申请人：GLAXO GROUP LTD

  公开号：WO2005080382A1

  公开（公告）日：2005-09-01

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl; or corresponds to a group R5; R2 is hydrogen or C1-4alkyl; R3 is C1-4alkyl; R4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; R5 is a moiety selected from the group consisting of: isoxazolyl, -CH2-N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; and when R1 is chlorine and p is 1, such R1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R1 corresponds to R5, p is 1; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D3 receptors, e.g. to treat drug dependency or as antipsychotic agents.

  本发明涉及公式(I)的新化合物或其药学上可接受的盐，其中G选自以下组成的一组：苯基、吡啶基、苯并噻唑基、吲哚基；p是一个从0到5的整数；R1独立地选自以下组成的一组：卤素、羟基、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基、卤代C1-4烷氧基、C1-4烷酰基；或对应于一个R5基团；R2是氢或C1-4烷基；R3是C1-4烷基；R4是氢，或苯基、杂环基、5-或6-成员杂芳基，或8-到11-成员双环基，其中任何一个基团可以选择地被来自以下组成的1、2、3或4个取代基所取代：卤素、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基、C1-4烷酰基；R5是选自以下组成的基团：异噁唑基、-CH2-N-吡咯基、1,1-二氧化-2-异噻唑啉基、噻吩基、噻唑基、吡啶基、2-吡咯烷基，这样的基团可以选择地被一个或两个取代基所取代，所述取代基选自：卤素、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基、C1-4烷酰基；当R1是氯且p为1时，该R1不位于与分子其余部分的连接键的邻位；当R1对应于R5时，p为1；它们的制备方法，用于这些方法的中间体，含有它们的药物组合物以及它们作为多巴胺D3受体调节剂在治疗中的用途，例如用于治疗药物依赖或作为抗精神病药物。
• 1,2,4-Triazolyl Azabicyclo[3.1.0]hexanes: A New Series of Potent and Selective Dopamine D₃ Receptor Antagonists
  作者：Fabrizio Micheli、Luca Arista、Giorgio Bonanomi、Frank E. Blaney、Simone Braggio、Anna Maria Capelli、Anna Checchia、Federica Damiani、Romano Di-Fabio、Stefano Fontana、Gabriella Gentile、Cristiana Griffante、Dieter Hamprecht、Carla Marchioro、Manolo Mugnaini、Jacqui Piner、Emiliangelo Ratti、Giovanna Tedesco、Luca Tarsi、Silvia Terreni、Angela Worby、Charles R. Ashby、Christian Heidbreder

  DOI：10.1021/jm901319p

  日期：2010.1.14

  The discovery of new highly potent and selective dopamine (DA) D3 receptor antagonists has recently allowed the characterization of the DA D3 receptor in a range of preclinical animal models of drug addiction. A novel series of 1,2,4-triazol-3-yl-azabicyclo[3.1.0]hexanes, members of which showed a high affinity and selectivity for the DA D3 receptor and excellent pharmacokinetic profiles, is reported

  最近发现了新的强效和选择性多巴胺（DA）D 3受体拮抗剂，这种药物可以在一系列成瘾的临床前动物模型中表征DA D 3受体。本文报道了一系列新的1,2,4-三唑-3-基-氮杂双环[3.1.0]己烷，其成员对DA D 3受体显示出高亲和力和选择性，并具有出色的药代动力学特征。该系列衍生物的成员显示出良好的口服生物利用度和脑渗透性，并且对DA D 3的体外亲和力和选择性非常高受体，以及在该受体上具有高的体外拮抗作用。该系列的几个成员还显着减弱了条件位置偏爱（CPP）对尼古丁和可卡因的表达。
• Use of Azabicyclo Hexane Derivatives
  申请人：Hamprecht Dieter

  公开号：US20090036461A1

  公开（公告）日：2009-02-05

  The present invention provides a new use of a compound of formula (I) or a pharmaceutically acceptable salt or solvate salt thereof: wherein: G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R 1 is independently selected from a group consisting of: halogen, hydroxyl, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl; or corresponds to a group R 5 ; R 2 is hydrogen or C 1-4 alkyl; R 3 I s C 1-4 alkyl; R 4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; R 5 is a moiety selected from the group consisting of: isoxazolyl, —CH 2 —N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; and when R 1 is chlorine and p is 1, such R 1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R 1 corresponds to R 5 , p is 1; in the manufacture of a medicament for the treatment of a somatoform disorder such as body dysmorphic disorder or hyperchondriasis, bulimia nervosa, anorexia nervosa, binge eating, paraphilia and nonparaphilic sexual addictions, Sydeham's chorea, torticollis, autism, a movement disorder including Tourette's syndrome; and in the manufacture of a medicament for the treatment of premature ejaculation.

  本发明提供了化合物(I)或其药学上可接受的盐或溶剂盐的新用途：其中：G选择自苯基、吡啶基、苯并噻唑基、吲哚基的群组;p为0至5的整数；R1独立地选择自卤素、羟基、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基、卤代C1-4烷氧基、C1-4酰基；或对应于R5基团；R2为氢或C1-4烷基；R3为C1-4烷基；R4为氢、苯基、杂环基、5-或6-成员杂芳基、或8-至11-成员双环基中的任何一种，其中任何一种基团均可选地被1、2、3或4个来自卤素、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基、C1-4酰基的取代基所取代；R5为从异恶唑基、—CH2—N-吡咯基、1,1-二氧化-2-异噻唑烷基、噻唑基、吡啶基、2-吡咯烷酰基中选择的基团，并且此类基团可选地被1或2个来自卤素、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基、C1-4酰基的取代基所取代；当R1为氯且p为1时，此类R1不位于与分子其余部分的连接键的正交位置；当R1对应于R5时，p为1；用于制造治疗躯体形式障碍（如身体畸形障碍或健忘症）、暴食症、厌食症、暴饮暴食、性变态和非性变态性瘾症、辛德汉舞蹈病、斜颈、自闭症、包括图雷特综合症在内的运动障碍的药物；以及用于制造治疗早泄的药物。
• Azabicyclo (3.1.0.) hexane derivatives useful as modulators of dopamine d3 receptors
  申请人：Arista Luca

  公开号：US20070142438A1

  公开（公告）日：2007-06-21

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: 1. wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R 1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, halo 1-4 alkoxy, C 1-4 alkanoyl; or corresponds to a group R 5 ; R 2 is hydrogen or C 1-4 alkyl; R 3 is C 1-4 alkyl; R 4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; R 5 is a moiety selected from the group consisting of: isoxazolyl, —CH 2 —N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C 1-4 alkyl, halo 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; and when R 1 is chlorine and p is 1, such R 1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R 1 corresponds to R 5 , p is 1; or a salt thereof which are useful as modulators of dopamine D 3 receptors, e.g. to treat drug dependency or as antipsychotic agents.

  本发明涉及公式（I）的新化合物或其药学上可接受的盐：1.其中G选自以下组中的一组：苯基，吡啶基，苯并噻唑基，吲哚基；p为0至5的整数；R1独立地选自以下组中的一组：卤素，羟基，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，卤代1-4烷氧基，C1-4酰基；或对应于R5基团；R2为氢或C1-4烷基；R3为C1-4烷基；R4为氢，苯基，杂环基，5-或6-成员杂芳基，或8-至11-成员双环基中的一种，其中任何一种基团均可选择性地被1、2、3或4个来自以下组的取代基所取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基；R5是从以下组中选择的一部分：异噁唑基，-CH2-N-吡咯基，1,1-二氧化-2-异硫氮基，噻唑基，噻唑基，吡啶基，2-吡咯烷基，这样的基团可以选择地被一个或两个取代基所取代：卤素，氰基，C1-4烷基，卤代1-4烷基，C1-4烷氧基，C1-4酰基；当R1为氯且p为1时，该R1不位于与分子的其余部分的连接键的邻位上；当R1对应于R5时，p为1；或其盐，它们可用作多巴胺D3受体的调节剂，例如用于治疗药物依赖或作为抗精神病药物。
• Azabicyclo (3.1.0) Hexane Derivatives Useful As Modulators Of Dopamine D3 Receptors
  申请人：Arista Luca

  公开号：US20100160336A1

  公开（公告）日：2010-06-24

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein G is selected from a group consisting of: phenyl, pyridyl, benzothiazolyl, indazolyl; p is an integer ranging from 0 to 5; R 1 is independently selected from a group consisting of: halogen, hydroxy, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl; or corresponds to a group R 5 ; R 2 is hydrogen or C 1-4 alkyl; R 3 is C 1-4 alkyl; R 4 is hydrogen, or a phenyl group, a heterocyclyl group, a 5- or 6-membered heteroaromatic group, or a 8- to 11-membered bicyclic group, any of which groups is optionally substituted by 1, 2, 3 or 4 substituents selected from the group consisting of: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; R 5 is a moiety selected from the group consisting of: isoxazolyl, —CH 2 —N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl, 2-pyrrolidinonyl, and such a group is optionally substituted by one or two substituents selected from: halogen, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkanoyl; and when R 1 is chlorine and p is 1, such R 1 is not present in the ortho position with respect to the linking bond to the rest of the molecule; and when R 1 corresponds to R 5 , p is 1; processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D 3 receptors, e.g. to treat drug dependency or as antipsychotic agents.

  本发明涉及式（I）的新化合物或其药学上可接受的盐： 其中， G选自以下组：苯基，吡啶基，苯并噻唑基，吲唑基； p为0至5的整数； R1独立地选自以下组：卤素，羟基，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，卤代C1-4烷氧基，C1-4酰基；或对应于R5基团； R2为氢或C1-4烷基； R3为C1-4烷基； R4为氢，苯基，杂环基，5-或6-成员杂芳基，或8-至11-成员双环基中的任意一种，其中任一基团均可选地被1、2、3或4个来自以下组的取代基所取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基； R5为以下组中选出的基团：异恶唑基，-CH2-N-吡咯基，1,1-二氧化-2-异噻唑啉基，噻唑基，噻唑啉基，吡啶基，2-吡咯烷酰基，该基团可选地被1或2个来自以下组的取代基所取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基； 当R1为氯且p为1时，该R1不在与分子的其余部分的连接键的正交位置上；当R1对应于R5时，p为1； 本发明还涉及制备这些化合物的方法、用于这些方法的中间体、含有它们的制药组合物以及其作为多巴胺D3受体调节剂的用途，例如用于治疗药物依赖或作为抗精神病药物。