3-[(3-chloropropyl)thio]-5-(3,4-difluorophenyl)-4-methyl-4H-1,2,4-triazole | 863681-31-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-[(3-chloropropyl)thio]-5-(3,4-difluorophenyl)-4-methyl-4H-1,2,4-triazole
• 英文别名: 3-(3-chloropropylsulfanyl)-5-(3,4-difluorophenyl)-4-methyl-1,2,4-triazole
• CAS: 863681-31-6
• 化学式: C₁₂H₁₂ClF₂N₃S
• 分子量: 303.763
• InChiKey: JTYIJNUNIZZGBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  56
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methyl-6,7,8,9-tetrahydro-5H-[1,3]oxazolo[4,5-h][3]benzazepine 、 3-[(3-chloropropyl)thio]-5-(3,4-difluorophenyl)-4-methyl-4H-1,2,4-triazole 在 potassium carbonate 、 sodium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-[3-[[5-(3,4-Difluorophenyl)-4-methyl-1,2,4-triazol-3-yl]sulfanyl]propyl]-2-methyl-5,6,8,9-tetrahydro-[1,3]oxazolo[4,5-h][3]benzazepine
  参考文献：
  名称：

  新的融合苯并enza庚因作为选择性D3受体拮抗剂。合成和生物学评估。第一部分：[h]-稠合三环系统。

  摘要：

  合成和SAR的一系列新的有效和选择性多巴胺D（3）受体拮抗剂的报道。据报道，在最近公开的1,2,4-三唑-3-基-硫丙基-四氢苯并ze庚因的支架上引入了三环[h]-稠合的苯并ze庚因部分。还报道了完整的大鼠药代动力学特征。

  DOI：

  10.1016/j.bmcl.2007.12.066
• 作为产物：
  描述：

  5-(3,4-difluorophenyl)-4-methyl-4H-1,2,4-triazole-3-thiol 、 1-溴-3-氯丙烷 在 sodium ethanolate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 3-[(3-chloropropyl)thio]-5-(3,4-difluorophenyl)-4-methyl-4H-1,2,4-triazole
  参考文献：
  名称：

  [EN] COMPOUNDS HAVING AFFINITY FOR DOPAMINE D3 RECEPTOR AND USES THEREOF
  [FR] COMPOSES PRESENTANT UNE AFFINITE POUR LE RECEPTEUR DE LA DOPAMINE D3 ET LEURS UTILISATIONS

  摘要：

  公开号：

  WO2005118549A3

文献信息

• [EN] 7-PYRAZOLYLBENZAZEPINES HAVING AFFINITY FOR D3 RECEPTOR<br/>[FR] 7-PYRAZOLYLBENZAZEPINES PRESENTANT UNE AFFINITE POUR LE RECEPTEUR D3
  申请人：GLAXO GROUP LTD

  公开号：WO2005123717A1

  公开（公告）日：2005-12-29

  Compounds of formula (I) or a salt thereof are disclosed (I): wherein R1 is pyrazolyl substituted by two or three substituents independently selected from halogen, C1-4alkyl and haloC1-4alkyl; R2 is hydrogen or methyl; and R3 is quinolinyl, oxazolyl or phenyl, each of which is optionally substituted by one or two halogen, C1-4alkyl or haloC1-4alkyl. Processes for preparation and uses of the compounds in medicine, for example for the treatment of schizophrenia or drug dependency, are also disclosed.

  公式（I）的化合物或其盐已被披露（I）：其中R1是嘧啶基，其上独立选择的两个或三个取代基分别来自卤素、C1-4烷基和卤代C1-4烷基；R2是氢或甲基；R3是喹啉基、噁唑基或苯基，每个基上可选择地取代一个或两个卤素、C1-4烷基或卤代C1-4烷基。还披露了制备这些化合物的方法以及在医学上的用途，例如用于治疗精神分裂症或药物依赖症。
• [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。
• TRIAZOLE DERIVATIVES AS MODULATORS OF DOPAMINE D3 RECEPTORS
  申请人：Bonanomi Giorgio

  公开号：US20090221593A1

  公开（公告）日：2009-09-03

  The present invention relates to novel compounds of formula (I) or a salt thereof: wherein: G is a 5- or 6-membered heteroaromatic group, or is a 9- or 10-membered bicyclic heteroaromatic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein G is not pyridyl, indazolyl or benzothiazolyl; 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 ; 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; 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.

  本发明涉及公式(I)或其盐的新化合物： 其中： G是5或6成员的杂环芳基，或是含有一或两个氮和氧杂原子的9或10成员的双环杂环芳基，其中G不是吡啶基，吲哚基或苯并噻唑基； p是整数，范围从0到4； R1独立地选择自以下群组：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SF5；或对应于R5群组； R2是氢或C1-4烷基； n是2或3； X是S或-CH2-； R3是C1-4烷基； R4是氢，苯基，杂环基，5或6成员的杂环芳基或8到11成员的双环基，其中任何一种群组都可以选择性地被1,2,3或4个卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基和C1-4烷酰基取代； R5是异噁唑基，-CH2-N-吡咯基，1,1-二氧化-2-异噻唑烷基，噻吩基，噻唑基，吡啶基或2-吡咯烷基，其中每个群组都可以选择性地被一个或两个卤素，氰基，C1-4烷基，卤代C1-4烷基，C1-4烷氧基和C1-4烷酰基取代； 本发明还涉及用于制备这些化合物的中间体，包含它们的制药组合物以及它们作为多巴胺D3受体调节剂的用途，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。
• 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。
• COMPOUNDS HAVING AFFINITY FOR DOPAMINE D3 RECEPTOR AND USES THEREOF"
  申请人：Bonanomi Giorgio

  公开号：US20100016287A1

  公开（公告）日：2010-01-21

  Compounds of formula (I) wherein A is a 5 or 6 membered heteroaromatic ring or a 5 or 6 membered heterocyclic ring, and which are useful for treating mental disorders such as schizophrenia are set out herein.

  本文介绍了式子（I）中A为5或6成员杂芳环或5或6成员杂环的化合物，可用于治疗精神障碍，如精神分裂症。