1-Methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane | 926907-00-8

• 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: 1-Methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane
• CAS: 926907-00-8
• 化学式: C₁₃H₁₄F₃N
• 分子量: 241.25
• InChiKey: YYMGTHCCSSYQLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[6-bromo-3,5-dioxo-4-(phenylcarbonyl)-4,5-dihydro-1,2,4-triazin-2(3H)-yl]propanal 、 1-Methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hexane 、 三乙酰氧基硼氢化钠 、 benzoyl nitrene 在 氯化铵 、 二氯甲烷 、 SiO2 、 methanol-dichloromethane 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 2.42h， 以affording 6-bromo-2-(3-{1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione (Enantiomer 2, 48 mg, 0.101 mmol, 17.73% yield) as a white powder的产率得到6-bromo-2-(3-{1-methyl-5-[4-(trifluoromethyl)phenyl]-3-azabicyclo[3.1.0]hex-3-yl}propyl)-1,2,4-triazine-3,5(2H,4H)-dione
  参考文献：
  名称：

  AZABICYCLO [3. 1. 0] HEXYL DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS

  摘要：

  本发明涉及一种式（I）的新化合物或其盐：其中G选自以下组中的一组：苯基，5-或6-成员的单环杂芳基团或8-至11-成员的杂芳双环基团；p为0至5的整数；R1为卤素，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酰基和SF5；或对应于R6基团；当p是2至5的整数时，每个R1可以相同或不同；R2为氢或C1-4烷基；n为3、4、5或6；R6为选自以下组中的基团：异氧唑基，-CH2-N-吡咯基，1,1-二氧杂氮环戊基，噻吩基，噻唑基，吡啶基，2-吡咯烷基，且此类R6基团可以被选自以下一种或两种取代基取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基；R4选自以下组中的一种：氢，卤素，羟基，氰基，C1-4烷基，C3-7环烷基，卤代C1-4烷基，C1-4烷氧基，卤代C1-4烷氧基，C1-4酰基和NR′R″；或R4为苯基，5-14成员的杂环基团；此类苯基或杂环基团可以被1、2、3或4个选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，卤代C1-4烷氧基和SF5；R7为氢或C1-2烷基；R′为H，C1-4烷基或C1-4酰基；R″被定义为R′；R′和R″与相互连接的氮原子一起可以形成5-，6-成员的饱和或不饱和杂环环；并且这些化合物可用于治疗，作为多巴胺D3受体的调节剂。

  公开号：

  US20100240661A1

文献信息

• [EN] AZABICYCLO [3. 1. 0] HEXYL DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2009043884A1

  公开（公告）日：2009-04-09

  The present invention relates to novel compounds of formula (I) or a salt thereof, wherein G is selected from a group consisting of: phenyl, a 5- or 6-membered monocyclic heteroaryl group, or a 8- to 11-membered heteroaryl bicyclic group; p is an integer ranging from 0 to 5; R1 is halogen, hydroxy, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and SF5; or corresponds to a group R6; and when p is an integer ranging from 2 to 5, each R1 may be the same or different; R2 is hydrogen or C1-4alkyl; n is 3, 4, 5 or 6; R6 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 R6 group is optionally substituted by one or two substituents selected from: halogen, cyano, C1-4alkyl, haloC1-4alkyl, C1-4alkoxy, C1-4alkanoyl; R4 is selected in the group consisting of: hydrogen, halogen, hydroxy, cyano, C1-4alkyl, C3-7 cycloalkyl, haloC1-4alkyl, C1-4alkoxy, haloC1-4alkoxy, C1-4alkanoyl and NR'R'; or R4 is a phenyl group, a 5-14 membered heterocyclic group; and any of such phenyl or heterocyclic group 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, haloC1-4alkoxy and SF5; R7 is hydrogen or C1-2alkyl; R' is H, C1-4 alkyl or C1-4 alkanoyl; R' is defined as R'; R' and R' taken together with the interconnecting nitrogen atom may form a 5-, 6-membered saturated or unsaturated heterocyclic ring; 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, as antipsychotic agents, to treat obsessive compulsive spectrum disorders, or premature ejaculation.

  本发明涉及式(I)的新化合物或其盐，其中G选自以下组成的一组：苯基，5-或6-成员单环杂环基，或8-至11-成员杂环双环基；p是一个从0到5的整数；R1是卤素，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烷酰基和SF5；或对应于一个R6基团；当p是一个从2到5的整数时，每个R1可以相同也可以不同；R2是氢或C1-4烷基；n是3、4、5或6；R6是从以下组成的基团中选择的一个：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，以及这样的R6基团可以选择地被来自以下组成的一个或两个取代基取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4烷酰基；R4在以下组成的基团中选择：氢，卤素，羟基，氰基，C1-4烷基，C3-7环烷基，卤代C1-4烷基，C1-4烷氧基，卤代C1-4烷氧基，C1-4烷酰基和NR'R'；或R4是一个苯基，一个5-14成员杂环基；和任何这样的苯基或杂环基可以选择地被来自以下组成的1、2、3或4个取代基取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4烷酰基，卤代C1-4烷氧基和SF5；R7是氢或C1-2烷基；R'是H，C1-4烷基或C1-4烷酰基；R'被定义为R'；R'和R'连同相互连接的氮原子可以形成一个5-、6-成员饱和或不饱和杂环环；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在治疗中的用途，作为多巴胺D3受体调节剂，例如用于治疗药物依赖，作为抗精神病药物，用于治疗强迫症谱系障碍，或早泄。
• Triazolyl Derivatives of Azabicyclo [3.1.0] Hexane as Dopamine D3 Receptor Modulators
  申请人：Capelli Anna Marie

  公开号：US20080242715A1

  公开（公告）日：2008-10-02

  The present invention relates to novel compounds of formula (IC) or a salt thereof: wherein: p is an integer ranging from 0 to 4; 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 SF 5 ; or corresponds to a group R 5 ; m 1 , m 2 , m 3 , and m 4 are 0; m 5 , m 6 and m 7 are each independently 0, 1 or 2 wherein the sum of m 5 , m 6 and m 7 is 1 or 2; R 6 is C 1-6 alkyl; R 7 is halogen, C 1-6 alkyl or haloC 1-6 alkyl; R 2 is hydrogen or C 1-4 alkyl; n is 2 or 3; X is S or —CH 2 —; 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 and C 1-4 alkanoyl; R 5 is isoxazolyl, —CH 2 —N-pyrrolyl, 1,1-dioxido-2-isothiazolidinyl, thienyl, thiazolyl, pyridyl or 2-pyrrolidinonyl, wherein each 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 and C 1-4 alkanoyl; with the proviso that when m 5 =m 6 =1 , R 7 is not chlorine; 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 substance related disorders, as antipsychotic agents, premature ejaculation or cognition impairment.

  本发明涉及式（IC）的新化合物或其盐：其中：p为0至4的整数；R1独立地选择自以下组：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SF5；或对应于R5基团；m1、m2、m3和m4为0；m5、m6和m7各自独立地为0、1或2，其中m5、m6和m7的和为1或2；R6为C1-6烷基；R7为卤素、C1-6烷基或卤代C1-6烷基；R2为氢或C1-4烷基；n为2或3；X为S或—CH2—；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，其中任何一个基团均可选为以下1、2、3或4个取代基：卤素、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基和C1-4酰基；R5为异噁唑基、—CH2—N-吡咯基、1,1-二氧化-2-异噻唑啉基、噻唑基、噻唑基、吡啶基或2-吡咯烷基，其中每个基团均可选为一个或两个取代基，所选取代基为：卤素、氰基、C1-4烷基、卤代C1-4烷基、C1-4烷氧基和C1-4酰基；但当m5=m6=1时，R7不为氯。本发明还涉及用于制备这些化合物的中间体，含有这些化合物的药物组合物以及它们在治疗中的用途，作为多巴胺D3受体调节剂，例如用于治疗物质相关障碍、作为抗精神病药物、早泄或认知障碍的治疗剂。
• AZABICYCLO [3. 1. 0] HEXYL DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS
  申请人：Bertani Barbara

  公开号：US20100240661A1

  公开（公告）日：2010-09-23

  The present invention relates to novel compounds of formula (I) or a salt thereof: wherein G is selected from a group consisting of: phenyl, a 5- or 6-membered monocyclic heteroaryl group, or a 8- to 11-membered heteroaryl bicyclic group; p is an integer ranging from 0 to 5; R 1 is halogen, hydroxy, cyano, C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl and SF 5 ; or corresponds to a group R 6 ; and when p is an integer ranging from 2 to 5, each R 1 may be the same or different; R 2 is hydrogen or C 1-4 alkyl; n is 3, 4, 5 or 6; R 6 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 R 6 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; R 4 is selected in the group consisting of: hydrogen, halogen, hydroxy, cyano, C 1-4 alkyl, C 3-7 cycloalkyl, haloC 1-4 alkyl, C 1-4 alkoxy, haloC 1-4 alkoxy, C 1-4 alkanoyl and NR′R″; or R 4 is a phenyl group, a 5-14 membered heterocyclic group; and any of such phenyl or heterocyclic group 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, haloC 1-4 alkoxy and SF 5 ; R 7 is hydrogen or C 1-2 alkyl; R′ is H, C 1-4 alkyl or C 1-4 alkanoyl; R″ is defined as R′; R′ and R″ taken together with the interconnecting nitrogen atom may form a 5-, 6-membered saturated or unsaturated heterocyclic ring; and their use in therapy, as modulators of dopamine D 3 receptors.

  本发明涉及一种式（I）的新化合物或其盐：其中G选自以下组中的一组：苯基，5-或6-成员的单环杂芳基团或8-至11-成员的杂芳双环基团；p为0至5的整数；R1为卤素，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酰基和SF5；或对应于R6基团；当p是2至5的整数时，每个R1可以相同或不同；R2为氢或C1-4烷基；n为3、4、5或6；R6为选自以下组中的基团：异氧唑基，-CH2-N-吡咯基，1,1-二氧杂氮环戊基，噻吩基，噻唑基，吡啶基，2-吡咯烷基，且此类R6基团可以被选自以下一种或两种取代基取代：卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基，C1-4酰基；R4选自以下组中的一种：氢，卤素，羟基，氰基，C1-4烷基，C3-7环烷基，卤代C1-4烷基，C1-4烷氧基，卤代C1-4烷氧基，C1-4酰基和NR′R″；或R4为苯基，5-14成员的杂环基团；此类苯基或杂环基团可以被1、2、3或4个选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，卤代C1-4烷氧基和SF5；R7为氢或C1-2烷基；R′为H，C1-4烷基或C1-4酰基；R″被定义为R′；R′和R″与相互连接的氮原子一起可以形成5-，6-成员的饱和或不饱和杂环环；并且这些化合物可用于治疗，作为多巴胺D3受体的调节剂。
• AZABICYCLO Ý3. 1. 0¨HEXYL DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS
  申请人：Glaxo Group Limited

  公开号：EP2205560A1

  公开（公告）日：2010-07-14
• AZABICYCLO [3. 1. 0]HEXYL DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS
  申请人：Glaxo Group Limited

  公开号：EP2205560B1

  公开（公告）日：2011-12-28