(S)-hexahydro-1H-pyridine [1,2-a]pyrazine-1,4(6H)-dione | 101392-99-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌嗪基哌啶类
• 英文名称: (S)-hexahydro-1H-pyridine [1,2-a]pyrazine-1,4(6H)-dione
• 英文别名: (S)-octahydro-1, 4-dioxo-2H-pyrido [1,2-a] pyrazine；(9aS)-octahydro-1H-pyrido[1,2-a]pyrazine-1,4-dione；(9aS)-3,6,7,8,9,9a-hexahydro-2H-pyrido[1,2-a]pyrazine-1,4-dione
• CAS: 101392-99-8
• 化学式: C₈H₁₂N₂O₂
• 分子量: 168.195
• InChiKey: YXBLPNSWHUPKPH-LURJTMIESA-N

物化性质

• 沸点：
  444.0±34.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-hexahydro-1H-pyridine [1,2-a]pyrazine-1,4(6H)-dione 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以68%的产率得到(9SS)-八氢-2-吡啶-吡嗪盐酸盐[1,2-A]
  参考文献：
  名称：

  设计，合成和吲哚-3-羧酰胺双环哌嗪类似物作为新型大麻素CB1受体激动剂的结构-活性关系研究

  摘要：

  合成双环哌嗪衍生物作为N-烷基哌嗪的构象约束类似物，发现其为有效的CB1受体激动剂。CB1受体激动剂活性取决于双环系统手性中心的绝对构型。尽管构象约束不能保护化合物免受N-去烷基化作用的代谢，但发现一些双环类似物比不受约束的先导化合物更有效。化合物8b在体内显示出有效的抗伤害感受活性。

  DOI：

  10.1016/j.bmcl.2010.10.061
• 作为产物：
  描述：

  (S)-methyl 2-(piperidin-2-amido)acetate 在 三乙胺 作用下， 以 甲醇 为溶剂， 反应 6.0h， 生成 (S)-hexahydro-1H-pyridine [1,2-a]pyrazine-1,4(6H)-dione
  参考文献：
  名称：

  设计，合成和吲哚-3-羧酰胺双环哌嗪类似物作为新型大麻素CB1受体激动剂的结构-活性关系研究

  摘要：

  合成双环哌嗪衍生物作为N-烷基哌嗪的构象约束类似物，发现其为有效的CB1受体激动剂。CB1受体激动剂活性取决于双环系统手性中心的绝对构型。尽管构象约束不能保护化合物免受N-去烷基化作用的代谢，但发现一些双环类似物比不受约束的先导化合物更有效。化合物8b在体内显示出有效的抗伤害感受活性。

  DOI：

  10.1016/j.bmcl.2010.10.061

文献信息

• 作为钾通道调节剂的化合物
  申请人：江苏先声药业有限公司

  公开号：CN108250128A

  公开（公告）日：2018-07-06

  本发明涉及一类作为钾通道调节剂的化合物，其为式(I)化合物或其药学上可接受的盐，所述化合物或其药学上可接受的盐对治疗和预防受钾离子通道的活性影响的疾病和病症有效果。
• [EN] TRICYCLIC 1-[(3-INDOL-3-YL)CARBONYL] PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS<br/>[FR] DERIVES TRICYCLIQUES DE PIPERAZINE 1-[(3-INDOL-3-YL)CARBONYL] UTILES EN TANT QU'AGONISTES DU RECEPTEUR CANNABINOIDE CB1
  申请人：AKZO NOBEL NV

  公开号：WO2005058327A1

  公开（公告）日：2005-06-30

  The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy and halogen; R1 is (C5-8)cycloalkyl; R2 is H or (C1-4)alkyl; R3, R3´, R4’ R4’, R5, R5’ and R6’ are independently hydrogen or (C1-4)-alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; R6 is hydrogen or (C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; or R6 forms together with R7 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; R7 forms together with R6 a 4-7 membered saturated heterocydic ring, optionally containing a further heteroatom selected from O and S; or R7 is H, (C1-4)alkyl or (C3-5)cycloalkyl, the alkyl groups being optionally substituted with OH, halogen or (C1-4)alkyloxy; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  该发明涉及具有通式（I）的三环1-[(吲哚-3-基)羰基]哌嗪衍生物，其中X为CH2、O或S；R代表1-3个取自H、(C1-4)烷基、(C1-4)烷氧基和卤素的取代基；R1为(C5-8)环烷基；R2为H或(C1-4)烷基；R3、R3'、R4'、R4'、R5、R5'和R6'独立地为氢或(C1-4)烷基，可选地取代为(C1-4)烷氧基、OH或卤素；R6为氢或(C1-4)烷基，可选地取代为(C1-4)烷氧基、OH或卤素；或R6与R7一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；R7与R6一起形成一个含有O和S等进一步杂原子的4-7元饱和杂环；或R7为H、(C1-4)烷基或(C3-5)环烷基，烷基基团可选地取代为OH、卤素或(C1-4)烷氧基；或其药学上可接受的盐。该发明还涉及包含所述三环1-[(吲哚-3-基)羰基]哌嗪衍生物的药物组合物，并且涉及在治疗疼痛，如围手术疼痛、慢性疼痛、神经痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛中使用这些衍生物。
• Tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives as cannabinoid cb1 receptor agonists
  申请人：Adam-Worrall Julia

  公开号：US20070088025A1

  公开（公告）日：2007-04-19

  The invention relates to tricyclic 1-[(in-dol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH 2 , O or S; R represents 1-3 substituents independently selected from H, (C 1-4 )alkyl, (C 1-4 )alkyloxy and halogen; R 1 is (C 5-8 )cycloalkyl; R 2 is H or (C 1-4 )alkyl; R 3 , R 3 ′, R 4 ′, R 4 ′, R 5 , R 5 ′ and R 6 ′ are independently hydrogen or (C 1-4 )-alkyl, optionally substituted with (C 1-4 )alkyloxy, OH or halogen; R 6 is hydrogen or (C 1-4 )alkyl, optionally substituted with (C 1-4 )alkyloxy, OH or halogen; or R 6 forms together with R 7 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; R 7 forms together with R 6 a 4-7 membered saturated heterocydic ring, optionally containing a further heteroatom selected from O and S; or R 7 is H, (C 1-4 )alkyl or (C 3-5 )cycloalkyl, the alkyl groups being optionally substituted with OH, halogen or (C 1-4 )alkyloxy; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  本发明涉及三环1-[(吲哚-3-基)羰基]哌嗪衍生物，其具有通式（I），其中X为CH2、O或S；R代表1-3个取自H、（C1-4）烷基、（C1-4）烷氧基和卤素的取代基；R1为（C5-8）环烷基；R2为H或（C1-4）烷基；R3、R3'、R4'、R4'、R5、R5'和R6'独立地为氢或（C1-4）烷基，可选地被（C1-4）烷氧基、OH或卤素取代；R6为氢或（C1-4）烷基，可选地被（C1-4）烷氧基、OH或卤素取代；或R6与R7形成4-7成员饱和杂环环，可选地包含进一步的选自O和S的杂原子；R7与R6a形成4-7成员饱和杂环环，可选地包含进一步的选自O和S的杂原子；或R7为H、（C1-4）烷基或（C3-5）环烷基，烷基基团可选地被OH、卤素或（C1-4）烷氧基取代；或其药学上可接受的盐。本发明还涉及含有上述三环1-[(吲哚-3-基)羰基]哌嗪衍生物的制药组合物，以及在治疗疼痛，如围手术期疼痛、慢性疼痛、神经病性疼痛、癌症疼痛和与多发性硬化症相关的疼痛和痉挛中使用这些衍生物的用途。
• Tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives as cannabinoid CB1 receptor agonists
  申请人：N.V. Organon

  公开号：US07772227B2

  公开（公告）日：2010-08-10

  The invention relates to tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivative having the general Formula (I) wherein X is CH2, O or S; R represents 1-3 substituents independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy and halogen; R1 is (C5-8)cycloalkyl; R2 is H or (C1-4)alkyl; R3, R3′, R4′ R4′, R5, R5′ and R6′ are independently hydrogen or (C1-4)-alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; R6 is hydrogen or (C1-4)alkyl, optionally substituted with (C1-4)alkyloxy, OH or halogen; or R6 forms together with R7 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; R7 forms together with R6 a 4-7 membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O and S; or R7 is H, (C1-4)alkyl or (C3-5)cycloalkyl, the alkyl groups being optionally substituted with OH, halogen or (C1-4)alkyloxy; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives, and to the use of these derivatives in the treatment of pain, such as peri-operative pain, chronic pain neuropathic pain, cancer pain, and pain and spasticity associated with multiple sclerosis.

  本发明涉及具有通式（I）的三环1-[(indol-3-yl)carbonyl]哌嗪衍生物，其中X为CH2、O或S；R代表1-3个取自H、(C1-4)烷基、(C1-4)烷氧基和卤素的取代基；R1为(C5-8)环烷基；R2为H或(C1-4)烷基；R3、R3′、R4′、R4′、R5、R5′和R6′独立地为氢或(C1-4)烷基，可选地取代(C1-4)烷氧基、OH或卤素；R6为氢或(C1-4)烷基，可选地取代(C1-4)烷氧基、OH或卤素；或R6与R7一起形成4-7成员饱和杂环环，可选地包含进一步从O和S选择的杂原子；R7与R6一起形成4-7成员饱和杂环环，可选地包含进一步从O和S选择的杂原子；或R7为H、(C1-4)烷基或(C3-5)环烷基，烷基基团可选地取代OH、卤素或(C1-4)烷氧基；或其药学上可接受的盐。本发明还涉及包含所述三环1-[(indol-3-yl)carbonyl]哌嗪衍生物的制药组合物，并且涉及使用这些衍生物治疗疼痛，例如围手术期疼痛、慢性疼痛、神经性疼痛、癌症疼痛以及与多发性硬化相关的疼痛和痉挛。
• TRICYCLIC 1-((3-INDOL-3-YL)CARBONYL)PIPERAZINE DERIVATIVES AS CANNABINOID CB1 RECEPTOR AGONISTS
  申请人：N.V. Organon

  公开号：EP1696930B1

  公开（公告）日：2007-04-11