Methyl (s)-2,3,11,11a-tetrahydro-1h,5h-pyrrolo[2,1-c][1,4]benzoxazepine-5-one-7-carboxylate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: Methyl (s)-2,3,11,11a-tetrahydro-1h,5h-pyrrolo[2,1-c][1,4]benzoxazepine-5-one-7-carboxylate
• 英文别名: methyl (6aS)-11-oxo-6a,7,8,9-tetrahydro-6H-pyrrolo[2,1-c][1,4]benzoxazepine-2-carboxylate
• 化学式: C₁₄H₁₅NO₄
• 分子量: 261.27
• InChiKey: HEYZTQOCOLMDOG-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (s)-7-Bromo-2,3,11,11a-tetrahydro-1h,5h-pyrrolo[2,1-c][1,4]-benzoxazepine-5-one 、 三乙胺 、 甲醇 、 水 、 二甲基亚砜 在 醋酸钯 、 1,3-双(二苯基膦)丙烷 氩 、 一氧化碳 、 three 、 乙酸乙酯 、 Sodium sulfate-III 、 乙醚 作用下， 反应 22.0h， 以gave methyl (S)-2,3,11,11a-tetrahydro-1H,5H-pyrrolo[2,1-c][1,4]benzoxazepine-5-one-7-carboxylate (3.13 g) as a white crystalline solid的产率得到Methyl (s)-2,3,11,11a-tetrahydro-1h,5h-pyrrolo[2,1-c][1,4]benzoxazepine-5-one-7-carboxylate
  参考文献：
  名称：

  BENZOXAPZEPINE DERIVATIVES AND THEIR USE AS AMPA RECEPTOR STIMULATORS

  摘要：

  本发明涉及一种具有一般式I的苯并噁唑啉衍生物，其中X代表CO或S02; R1、R2、R3和R4独立地选择自H、(C1-4)烷基、(C1-4)烷氧基、(C1-4)烷氧基(C1-4)烷基、卤素、硝基、氰基、NR8R9、NR8COR10和CONR8R9，R5、R6和R7独立地为H或(C1-4)烷基; R8和R9独立地为H或(C1-4)烷基; 或R8和R9与它们所结合的氮原子一起形成一个5-或6-成员饱和杂环环，可选含有进一步选择自O、S或NR11的杂原子; R10为(C1-4)烷基; R11为(C1-4)烷基; A代表4-7成员饱和杂环环的残基，可选含有氧原子，该环可选地用1-3个取代基选择自(C1-4)烷基、(C1-4)烷氧基、羟基、卤素和氧代基取代; 或其药学上可接受的盐。本发明还涉及包含所述衍生物的制药组合物，以及利用这些苯并噁唑啉衍生物治疗中枢神经系统中介导AMPA受体的突触反应增强的神经疾病和精神障碍的用途。

  公开号：

  US20080139529A1

文献信息

• Benzoxazepines derivatives and their use as ampa receptor stimulators
  申请人：——

  公开号：US20040171605A1

  公开（公告）日：2004-09-02

  The present invention relates to benzoxazepine derivative having the general formula I, wherein X represents CO or SO 2 ; R 1 , R 2 , R 3 and R 4 are independently selected from H, (C 1-4 )alkyl, (C 1-4 )alkyloxy, (C 1-4 )alkyloxy(C 1-4 )alkyl, halogen, nitro, cyano, NR 8 R 9 , NR 8 COR 10 , and CONR 8 R 9 , R 5 , R 6 and R 7 are independently H or (C 1-4 )alkyl; R 8 and R 9 are independently H or (C 1-4 )alkyl; or R 8 and R 9 form together with the nitrogen atom to which they are bound a 5- or 6-membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O, S or NR 11 ; R 10 is (C 1-4 )alkyl; R 11 is (C 1-4 )alkyl; A represents the residue of a 4-7 membered saturated heterocyclic ring, optionally containing an oxygen atom, the ring being optionally substituted with 1-3 substituents selected from (C 1-4 )alkyl, (C 1-4 )alkyloxy, hydroxy, halogen and oxo; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, and to the use of these benzoxazepine derivatives in the treatment of neurological diseases and psychiatric disorders which are responsive to enhancement of synaptic responses mediated by AMPA receptors in the central nervous system. 1

  本发明涉及具有通式I的苯并噁唑衍生物，其中X代表CO或SO2；R1、R2、R3和R4分别选自H，(C1-4)烷基，(C1-4)烷氧基，(C1-4)烷氧基(C1-4)烷基，卤素，硝基，氰基，NR8R9，NR8COR10和CONR8R9，R5、R6和R7分别为H或(C1-4)烷基；R8和R9分别为H或(C1-4)烷基；或者R8和R9与它们所连接的氮原子一起形成一个5-或6-成员饱和杂环环，可选地含有进一步的杂原子，所述杂原子选自O、S或NR11；R10为(C1-4)烷基；R11为(C1-4)烷基；A代表4-7成员饱和杂环环的残基，可选地含有一个氧原子，该环可选地被1-3个取代基取代，所述取代基选自(C1-4)烷基，(C1-4)烷氧基，羟基，卤素和氧代基；或其药学上可接受的盐。本发明还涉及包含所述衍生物的制药组合物，以及在治疗中枢神经系统中响应于增强由AMPA受体介导的突触反应的神经疾病和精神障碍中使用这些苯并噁唑衍生物。
• Benzoxazepines derivatives and their use as AMPA receptor stimulators
  申请人：N.V. Organon

  公开号：US07307073B2

  公开（公告）日：2007-12-11

  The present invention relates to benzoxazepine derivative having the general formula I, wherein X represents CO or SO2; R1, R2, R3 and R4 are independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, halogen, nitro, cyano, NR8R9, NR8COR10, and CONR8R9, R5, R6 and R7 are independently H or (C1-4)alkyl; R8 and R9 are independently H or (C1-4)alkyl; or R8 and R9 form together with the nitrogen atom to which they are bound a 5- or 6-membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O, S or NR11; R10 is (C1-4)alkyl; R11 is (C1-4)alkyl; A represents the residue of a 4-7 membered saturated heterocyclic ring, optionally containing an oxygen atom, the ring being optionally substituted with 1-3 substituents selected from (C1-4)alkyl, (C1-4)alkyloxy, hydroxy, halogen and oxo; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, and to the use of these benzoxazepine derivatives in the treatment of neurological diseases and psychiatric disorders which are responsive to enhancement of synaptic responses mediated by AMPA receptors in the central nervous system

  本发明涉及具有一般式I的苯并噁唑啉衍生物，其中X代表CO或SO2；R1、R2、R3和R4分别选自H、(C1-4)烷基、(C1-4)烷氧基、(C1-4)烷氧基(C1-4)烷基、卤素、硝基、氰基、NR8R9、NR8COR10和CONR8R9，R5、R6和R7分别为H或(C1-4)烷基；R8和R9分别为H或(C1-4)烷基；或R8和R9与它们所连接的氮原子一起形成一个5-或6-成员饱和杂环环，可以选择地包含另一个杂原子，所述杂原子选自O、S或NR11；R10为(C1-4)烷基；R11为(C1-4)烷基；A代表4-7成员饱和杂环环的残基，可以选择地包含一个氧原子，该环可以选择地用1-3个取代基选自(C1-4)烷基、(C1-4)烷氧基、羟基、卤素和氧代基进行取代；或其药学上可接受的盐。该发明还涉及包括上述衍生物的制药组合物，以及在治疗中枢神经系统中介导的AMPA受体的突触反应增强性响应的神经学疾病和精神障碍的应用。
• Benzoxazepine derivatives and their use as AMPA receptor stimulators
  申请人：N.V. Organon

  公开号：US07504390B2

  公开（公告）日：2009-03-17

  The present invention relates to benzoxazepine derivative having the general formula I, wherein X represents CO or SO2; R1, R2, R3 and R4 are independently selected from H, (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, halogen, nitro, cyano, NR8R9, NR8COR10, and CONR8R9, R5, R6 and R7 are independently H or (C1-4)alkyl; R8 and R9 are independently H or (C1-4)alkyl; or R8 and R9 form together with the nitrogen atom to which they are bound a 5- or 6-membered saturated heterocyclic ring, optionally containing a further heteroatom selected from O, S or NR11; R10 is (C1-4)alkyl; R11 is (C1-4)alkyl; A represents the residue of a 4-7 membered saturated heterocyclic ring, optionally containing an oxygen atom, the ring being optionally substituted with 1-3 substituents selected from (C1-4)alkyl, (C1-4)alkyloxy, hydroxy, halogen and oxo; or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said derivatives, and to the use of these benzoxazepine derivatives in the treatment of neurological diseases and psychiatric disorders which are responsive to enhancement of synaptic responses mediated by AMPA receptors in the central nervous system.

  本发明涉及具有一般式I的苯并噁唑啉衍生物，其中X代表CO或SO2；R1、R2、R3和R4分别独立选择自H、（C1-4）烷基、（C1-4）烷氧基、（C1-4）烷氧基（C1-4）烷基、卤素、硝基、氰基、NR8R9、NR8COR10和CONR8R9，R5、R6和R7分别独立选择自H或（C1-4）烷基；R8和R9分别独立选择自H或（C1-4）烷基；或R8和R9与它们所连接的氮原子一起形成一个5-或6-成员饱和杂环环，可选地含有进一步从O、S或NR11中选择的杂原子；R10为（C1-4）烷基；R11为（C1-4）烷基；A表示4-7成员饱和杂环环的残基，可选地含有一个氧原子，该环可选地用1-3个选择自（C1-4）烷基、（C1-4）烷氧基、羟基、卤素和氧代的取代基进行取代；或其药学上可接受的盐。本发明还涉及包含所述衍生物的制药组合物，以及在治疗中使用这些苯并噁唑啉衍生物来增强中枢神经系统中由AMPA受体介导的突触反应的神经疾病和精神障碍的方法。