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1. 发明授权

US07700634B2 (Indol-3-yl) heterocycle derivatives as agonists of the cannabinoid CB1 receptor 失效
标题翻译：（吲哚-3-基）杂环衍生物作为大麻素CB1受体的激动剂
公开(公告)号：US07700634B2
公开(公告)日：2010-04-20
申请号：US10590674
申请日：2005-02-28
申请人： Julia Adam-Worrall , Angus John Morrison , Grant Wishart , Takao Kiyoi , Duncan Robert McArthur
发明人： Julia Adam-Worrall , Angus John Morrison , Grant Wishart , Takao Kiyoi , Duncan Robert McArthur
IPC分类号： A01N43/82 , A01N43/78 , C07D285/08 , C07D271/06 , C07D277/04
CPC分类号： C07D403/04 , C07D409/04 , C07D413/04 , C07D413/14 , C07D417/04 , C07D417/14 , C07D513/04
摘要： Disclosed herein are indole derivatives of the formula (I) wherein each of the substitutents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the indole derivatives and use of the derivatives for the treatment of pain.
摘要翻译：本文公开的是式（I）的吲哚衍生物，其中每个取代基被给出如说明书和权利要求书中阐述的定义。还公开了含有吲哚衍生物的药物组合物和用于治疗疼痛的衍生物的用途。

2. 发明授权

US07763732B2 Indole derivatives 失效
标题翻译：吲哚衍生物
公开(公告)号：US07763732B2
公开(公告)日：2010-07-27
申请号：US11506579
申请日：2006-08-18
申请人： Paul David Ratcliffe , Julia Adam-Worrall , Angus John Morrison , Stuart John Francis , Takao Kiyoi
发明人： Paul David Ratcliffe , Julia Adam-Worrall , Angus John Morrison , Stuart John Francis , Takao Kiyoi
IPC分类号： C07D285/08 , C07D271/10 , C07D211/06
CPC分类号： C07D413/14 , C07D417/14
摘要： Disclosed herein are indole derivatives of the formula (I) wherein each of the substitutents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the indole derivatives and use of the derivatives for the treatment of pain.
摘要翻译：本文公开的是式（I）的吲哚衍生物，其中每个取代基被给出如说明书和权利要求书中阐述的定义。还公开了含有吲哚衍生物的药物组合物和用于治疗疼痛的衍生物的用途。

3. 发明申请

US20070142446A1 (Indol-3-yl) heterocycle derivatives as a agonists of the cannabinoid cb1 receptor 失效
标题翻译：（吲哚-3-基）杂环衍生物作为大麻素cb1受体的激动剂
公开(公告)号：US20070142446A1
公开(公告)日：2007-06-21
申请号：US10590674
申请日：2005-02-28
申请人： Julia Adam-Worrall , Angus Morrison , Grant Wishart , Takao Kiyoi , Duncan McArthur
发明人： Julia Adam-Worrall , Angus Morrison , Grant Wishart , Takao Kiyoi , Duncan McArthur
IPC分类号： A61K31/433 , A61K31/427 , C07D417/14
CPC分类号： C07D403/04 , C07D409/04 , C07D413/04 , C07D413/14 , C07D417/04 , C07D417/14 , C07D513/04
摘要： Disclosed herein are indole derivatives of the formula (I) wherein each of the substitutents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the indole derivatives and use of the derivatives for the treatment of pain.
摘要翻译：本文公开的是式（I）的吲哚衍生物，其中每个取代基被给出如说明书和权利要求书中阐述的定义。还公开了含有吲哚衍生物的药物组合物和用于治疗疼痛的衍生物的用途。

4. 发明申请

US20070082931A1 Indole derivatives 失效
标题翻译：吲哚衍生物
公开(公告)号：US20070082931A1
公开(公告)日：2007-04-12
申请号：US11506579
申请日：2006-08-18
申请人： Paul Ratcliffe , Julia Adam-Worrall , Angus Morrison , Stuart Francis , Takao Kiyoi
发明人： Paul Ratcliffe , Julia Adam-Worrall , Angus Morrison , Stuart Francis , Takao Kiyoi
IPC分类号： A61K31/433 , A61K31/4245 , A61K31/427 , A61K31/422 , C07D417/14 , C07D413/14
CPC分类号： C07D413/14 , C07D417/14
摘要： Disclosed herein are indole derivatives of the formula (I) wherein each of the substitutents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing the indole derivatives and use of the derivatives for the treatment of pain.
摘要翻译：本文公开的是式（I）的吲哚衍生物，其中每个取代基被给出如说明书和权利要求书中阐述的定义。还公开了含有吲哚衍生物的药物组合物和用于治疗疼痛的衍生物的用途。

5. 发明申请

US20050250760A1 1-[(Indol-3-yl)carbonyl]piperazine derivatives 失效
标题翻译： 1 - [（吲哚-3-基）羰基]哌嗪衍生物
公开(公告)号：US20050250760A1
公开(公告)日：2005-11-10
申请号：US10518279
申请日：2003-06-13
申请人： Phillip Cowley , Wilson Caulfield , Jason Tierney , James Cairns , Julia Adam-Worrall , Mark York
发明人： Phillip Cowley , Wilson Caulfield , Jason Tierney , James Cairns , Julia Adam-Worrall , Mark York
IPC分类号： A61K31/405 , A61K31/496 , A61K31/4985 , A61P1/08 , A61P1/14 , A61P9/00 , A61P11/00 , A61P25/00 , A61P25/04 , A61P25/06 , A61P25/08 , A61P25/20 , A61P25/22 , A61P25/28 , A61P27/06 , A61P29/00 , A61P29/02 , A61P37/08 , C07D209/12 , C07D209/42 , C07D403/06 , C07D471/04 , C07D487/04 , A61K31/55 , A61K31/5377 , A61K31/541 , C07D413/14 , C07D417/14 , C07D43/14
CPC分类号： C07D471/04 , C07D209/42 , C07D487/04
摘要： The present invention relates to 1-[(indol-3-yl)carbonyl]piperazine derivative according to the general formula I or a pharmaceutically acceptable salt thereof. The invention also relates to pharmaceutical compositions comprising said 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.
摘要翻译：本发明涉及根据通式I的1 - [（吲哚-3-基）羰基]哌嗪衍生物或其药学上可接受的盐。本发明还涉及包含所述1 - [（吲哚-3-基）羰基]哌嗪衍生物的药物组合物，以及这些衍生物在治疗疼痛中的用途，例如手术前疼痛，慢性疼痛神经性疼痛，癌症疼痛，与多发性硬化相关的疼痛和痉挛状态。

6. 发明授权

US07772227B2 Tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives as cannabinoid CB1 receptor agonists 有权
标题翻译：三环1 - [（吲哚-3-基）羰基]哌嗪衍生物作为大麻素CB1受体激动剂
公开(公告)号：US07772227B2
公开(公告)日：2010-08-10
申请号：US10583013
申请日：2004-12-13
申请人： Julia Adam-Worrall
发明人： Julia Adam-Worrall
IPC分类号： A61K31/5365 , A61K31/496 , A61K31/4985
CPC分类号： C07D471/06
摘要： 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.
摘要翻译：本发明涉及具有通式（I）的三环1 - [（吲哚基-3-基）羰基]哌嗪衍生物，其中X是CH 2，O或S; R代表独立地选自H，（C 1-4）烷基，（C 1-4）烷氧基和卤素的1-3个取代基; R1是（C5-8）环烷基; R2是H或（C1-4）烷基; R 3，R 3'，R 4'R 4'，R 5，R 5'和R 6'独立地为氢或（C 1-4） - 烷基，任选被（C 1-4）烷氧基，OH或卤素取代; R 6是氢或任选被（C 1-4）烷氧基，OH或卤素取代的（C 1-4）烷基; 或R6与R7一起形成4-7元饱和杂环，任选地含有选自O和S的另外的杂原子; R7与R6一起形成4-7元饱和杂环，任选地含有另外选自O和S的杂原子; 或者R 7为H，（C 1-4）烷基或（C 3-5）环烷基，该烷基任选被OH，卤素或（C 1-4）烷氧基取代; 或其药学上可接受的盐。本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，以及这些衍生物在治疗疼痛中的用途，例如手术前疼痛，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状态。

7. 发明申请

US20090163473A1 (PYRIDO/THIENO)-[f]-OXAZEPINE-5-ONE DERIVATIVES 失效
标题翻译：（吡咯烷酮/噻吩） - [f] -OXAZEPINE-5-ONE衍生物
公开(公告)号：US20090163473A1
公开(公告)日：2009-06-25
申请号：US12389968
申请日：2009-02-20
申请人： Simon James Anthony Grove , Julia Adam-Worrall , Mingqiang Zhang , Robert Gilfillan
发明人： Simon James Anthony Grove , Julia Adam-Worrall , Mingqiang Zhang , Robert Gilfillan
IPC分类号： A61K31/553 , A61P25/24 , A61P25/28
CPC分类号： C07D498/14
摘要： The present invention relates to (pyrido/thieno)-[f]-oxazepine-5-one derivatives having the general Formula I wherein R1, R2 and R3 are independently H or (C1-4)alkyl; Ar represents a fused thiophene or pyridine ring optionally substituted with one or more substituents selected from (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, CF3, halogen, nitro, cyano, NR4R5, NR4COR6, and CONR4R5; R4 and R5 are independently H or (C1-4)-alkyl; or R4 and R5 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 NR6; R6 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 (pyrido/thieno)-[f]-oxazepine-5-one 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.
摘要翻译：本发明涉及具有通式I的（吡啶并噻吩并[f] - 氧氮杂-5-酮衍生物，其中R 1，R 2和R 3独立地为H或（C 1-4）烷基; Ar表示任选被一个或多个选自（C 1-4）烷基，（C 1-4）烷氧基，（C 1-4）烷氧基（C 1-4）烷基，CF 3，卤素，硝基，氰基，NR4R5，NR4COR6和CONR4R5; R 4和R 5独立地为H或（C 1-4） - 烷基; 或R 4和R 5与它们所连接的氮原子一起形成5-或6-元饱和杂环，任选地含有选自O，S或NR 6的另外的杂原子; R6是（C1-4）烷基; A表示任选含有氧原子的4-7元饱和杂环的残基，该环任选被1-3个选自（C 1-4）烷基，（C 1-4） - 烷氧基，羟基，卤素和氧代; 或其药学上可接受的盐。本发明还涉及包含所述衍生物的药物组合物，以及这些（吡啶并噻吩并[f] - 氧氮杂-5-酮衍生物在治疗对增强突触反应有反应的神经疾病和精神疾病的用途中的用途）由AMPA受体介导的中枢神经系统。

8. 发明申请

US20090029984A1 SYNERGISTIC COMBINATION FOR THE TREATMENT OF PAIN (CANNABINOID RECEPTOR AGONIST AND OPIOID RECEPTOR AGONIST) 审中-公开
标题翻译：用于治疗疼痛的协同组合（CANNABINOID受体激动剂和阿片受体激动剂）
公开(公告)号：US20090029984A1
公开(公告)日：2009-01-29
申请号：US11995243
申请日：2006-07-06
申请人： Julia Adam-Worrall , David Robert Hill , Jean Cottney
发明人： Julia Adam-Worrall , David Robert Hill , Jean Cottney
IPC分类号： A61K31/485 , A61K31/5377 , A61K31/445 , A61K31/135 , A61P29/00
CPC分类号： A61K31/135 , A61K31/137 , A61K31/4468 , A61K31/485 , A61K31/517 , A61K45/06 , A61K2300/00
摘要： The invention relates to a pharmaceutical dosage form comprising an analgesic combination for simultaneous or sequential use which comprises a peripherally restricted cannabinoid CB1 receptor agonist having a brain Cmax to plasma Cmax ratio of less than 0.1 and an opioid receptor agonist, as well as to a method for treating pain using said pharmaceutical dosage form.
摘要翻译：本发明涉及一种药物剂型，其包含用于同时或顺序使用的止痛组合物，其包含具有脑C max至血浆C max比小于0.1的外周限制性大麻素CB1受体激动剂和阿片受体激动剂，以及方法用于使用所述药物剂型治疗疼痛。

9. 发明授权

US08034804B2 (Pyrido/thieno)-[f]-oxazepine-5-one derivatives 失效
标题翻译：（吡啶并噻吩） - [f] - 氧氮杂-5-酮衍生物
公开(公告)号：US08034804B2
公开(公告)日：2011-10-11
申请号：US12389968
申请日：2009-02-20
申请人： Simon James Anthony Grove , Julia Adam-Worrall , Mingqiang Zhang , Robert Gilfillan
发明人： Simon James Anthony Grove , Julia Adam-Worrall , Mingqiang Zhang , Robert Gilfillan
IPC分类号： A61K31/553 , A61P25/28
CPC分类号： C07D498/14
摘要： The present invention relates to (pyrido/thieno)-[f]-oxazepine-5-one derivatives having the general Formula I wherein R1, R2 and R3 are independently H or (C1-4)alkyl; Ar represents a fused thiophene or pyridine ring optionally substituted with one or more substituents selected from (C1-4)alkyl, (C1-4)alkyloxy, (C1-4)alkyloxy(C1-4)alkyl, CF3, halogen, nitro, cyano, NR4R5, NR4COR6, and CONR4R5; R4 and R5 are independently H or (C1-4)-alkyl; or R4 and R5 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 NR6; R6 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 (pyrido/thieno)-[f]-oxazepine-5-one 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.
摘要翻译：本发明涉及具有通式I的（吡啶并噻吩并[f] - 氧氮杂-5-酮衍生物，其中R 1，R 2和R 3独立地为H或（C 1-4）烷基; Ar表示任选被一个或多个选自（C 1-4）烷基，（C 1-4）烷氧基，（C 1-4）烷氧基（C 1-4）烷基，CF 3，卤素，硝基，氰基，NR4R5，NR4COR6和CONR4R5; R4和R5独立地是H或（C1-4） - 烷基; 或R 4和R 5与它们所连接的氮原子一起形成5-或6-元饱和杂环，任选地含有选自O，S或NR 6的另外的杂原子; R6是（C1-4）烷基; A表示任选含有氧原子的4-7元饱和杂环的残基，该环任选被1-3个选自（C 1-4）烷基，（C 1-4） - 烷氧基，羟基，卤素和氧代; 或其药学上可接受的盐。本发明还涉及包含所述衍生物的药物组合物，以及这些（吡啶并噻吩并[f] - 氧氮杂-5-酮衍生物在治疗对增强突触反应有反应的神经疾病和精神疾病的用途中的用途）由AMPA受体介导的中枢神经系统。

10. 发明申请

US20070088025A1 Tricyclic 1-[(indol-3-yl)carbonyl]piperazine derivatives as cannabinoid cb1 receptor agonists 有权
公开(公告)号：US20070088025A1
公开(公告)日：2007-04-19
申请号：US10583013
申请日：2004-12-13
申请人： Julia Adam-Worrall
发明人： Julia Adam-Worrall
IPC分类号： A61K31/542 , A61K31/5383 , A61K31/496 , C07D498/04 , C07D491/04 , C07D471/04
CPC分类号： C07D471/06
摘要： The invention relates to tricyclic 1-[(in-dol-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 R7a 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.

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