公开(公告)号：US5741809A

公开(公告)日：1998-04-21

申请号：US466332

申请日：1995-06-06

申请人： Tesfaye Biftu ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  T. Y. Shen

发明人： Tesfaye Biftu ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  T. Y. Shen

IPC分类号： C07D333/06 ,  A61K31/17 ,  A61K31/34 ,  A61K31/341 ,  A61K31/38 ,  A61K31/381 ,  A61K31/44 ,  A61K31/443 ,  A61P1/00 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P17/00 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P43/00 ,  C07C291/02 ,  C07D207/09 ,  C07D307/12 ,  C07D307/14 ,  C07D307/52 ,  C07D333/16 ,  C07D333/18 ,  C07D333/20 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14

CPC分类号： C07D405/04 ,  C07D207/09 ,  C07D307/12 ,  C07D307/14 ,  C07D333/16 ,  C07D333/18 ,  C07D333/20 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  Y10S514/825 ,  Y10S514/826 ,  Y10S514/863 ,  Y10S514/912 ,  Y10S514/914 ,  Y10S514/921 ,  Y10S514/925

摘要： 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. Also disclosed is a method to treat disorders mediated by PAF and/or leukotrienes that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, to a patient in need of such therapy.

摘要翻译： 公开了2,5-二芳基四氢呋喃，2,5-二芳基四氢噻吩，1,3-二芳基环戊烷，其减少趋化性和呼吸道爆发，导致在炎性或免疫反应期间形成多形核白细胞的有害氧自由基。 该化合物通过作为PAF受体拮抗剂，通过抑制酶5-脂氧合酶，或通过显示双重活性，即作为PAF受体拮抗剂和5-脂肪氧合酶抑制剂两者而表现出该生物学活性。 还公开了一种治疗由PAF和/或白三烯介导的病症的方法，其包括向有需要的患者施用有效量的一种或多种上述化合物或其药学上可接受的盐，任选地在药学上可接受的载体中 的这种疗法。

公开(公告)号：US06420392B1

公开(公告)日：2002-07-16

申请号：US08669371

申请日：1996-10-09

申请人： Tesfaye Biftu ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  T Y Shen

发明人： Tesfaye Biftu ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  T Y Shen

IPC分类号： A01N4306

CPC分类号： C07D405/04 ,  C07D207/09 ,  C07D307/12 ,  C07D307/14 ,  C07D333/16 ,  C07D333/18 ,  C07D333/20 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  Y10S514/825 ,  Y10S514/826 ,  Y10S514/863 ,  Y10S514/912 ,  Y10S514/914 ,  Y10S514/921 ,  Y10S514/925

摘要： 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. Also disclosed is a method to treat disorders mediated by PAF and/or leukotrienes that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, to a patient in need of such therapy.

摘要翻译： 公开了2,5-二芳基四氢呋喃，2,5-二芳基四氢噻吩，1,3-二芳基环戊烷，其减少趋化性和呼吸道爆发，导致在炎性或免疫反应期间形成多形核白细胞的有害氧自由基。 该化合物通过作为PAF受体拮抗剂，通过抑制酶5-脂氧合酶，或通过显示双重活性，即作为PAF受体拮抗剂和5-脂肪氧合酶抑制剂两者而表现出该生物学活性。 还公开了一种治疗由PAF和/或白三烯介导的病症的方法，其包括向有需要的患者施用有效量的一种或多种上述化合物或其药学上可接受的盐，任选地在药学上可接受的载体中 的这种疗法。

公开(公告)号：US06201016B1

公开(公告)日：2001-03-13

申请号：US08390641

申请日：1995-02-17

申请人： Xiong Cai ,  Gurmit Grewal ,  Sajjat Hussoin ,  Aberra Fura ,  Ralph Scannell ,  Tesfaye Biftu

发明人： Xiong Cai ,  Gurmit Grewal ,  Sajjat Hussoin ,  Aberra Fura ,  Ralph Scannell ,  Tesfaye Biftu

IPC分类号： A61K3134

CPC分类号： C07D307/14 ,  C07D471/04

摘要： Enantiomerically enriched disubstituted tetrahydrofurans, tetrahydrothiophenes, pyrrolidines and cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i. e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. It has been determined that 5-lipoxygenase activity, oral availability, and stability in vivo (for example, glucuronidation rate) can vary significantly among the optical isomers of the disclosed compounds.

摘要翻译： 公开了对映体富集的二取代的四氢呋喃，四氢噻吩，吡咯烷和环戊烷，其减少趋化性和呼吸道爆发，导致在炎性或免疫反应期间形成多形核白细胞的有害氧自由基。 通过作为PAF受体拮抗剂，通过抑制酶5-脂氧合酶，或通过显示双重活性，化合物表现出这种生物学活性， 例如通过作为PAF受体拮抗剂和5-脂加氧酶抑制剂两者。已经确定5-脂氧合酶活性，口服可利用性和体内稳定性（例如葡糖苷酸化速率）可以在光学异构体 所公开的化合物。

公开(公告)号：US5681966A

公开(公告)日：1997-10-28

申请号：US485096

申请日：1995-06-07

申请人： Xiong Cai ,  Gurmit Grewal ,  Sajjat Hussoin ,  Aberra Fura ,  Ralph Scannell ,  Tesfaye Biftu

发明人： Xiong Cai ,  Gurmit Grewal ,  Sajjat Hussoin ,  Aberra Fura ,  Ralph Scannell ,  Tesfaye Biftu

IPC分类号： C07D307/14 ,  C07D471/04 ,  C07D333/22 ,  A61K31/34 ,  A61K31/38 ,  C07D307/02

CPC分类号： C07D471/04 ,  C07D307/14

摘要： Enantiomerically enriched disubstituted tetrahydrofurans, tetrahydrothiophenes, pyrrolidines and cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i.e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. It has been determined that 5-lipoxygenase activity, oral availability, and stability in vivo (for example, glucuronidation rate) can vary significantly among the optical isomers of the disclosed compounds.

摘要翻译： 公开了对映体富集的二取代的四氢呋喃，四氢噻吩，吡咯烷和环戊烷，其减少趋化性和呼吸道爆发，导致在炎性或免疫反应期间形成多形核白细胞的有害氧自由基。 该化合物通过作为PAF受体拮抗剂，通过抑制酶5-脂氧合酶，或通过显示双重活性，即作为PAF受体拮抗剂和5-脂肪氧合酶抑制剂两者而表现出该生物学活性。 已经确定，所公开的化合物的光学异构体中的5-脂氧合酶活性，口服可利用性和体内稳定性（例如葡糖苷酸化速率）可以显着变化。

公开(公告)号：US5463083A

公开(公告)日：1995-10-31

申请号：US178222

申请日：1994-01-06

申请人： Tesfaye Biftu ,  Xiong Cai ,  Sajjet Hussion ,  Gurmit Grewal ,  T. Y. Shen

发明人： Tesfaye Biftu ,  Xiong Cai ,  Sajjet Hussion ,  Gurmit Grewal ,  T. Y. Shen

IPC分类号： C07D333/06 ,  A61K31/17 ,  A61K31/34 ,  A61K31/341 ,  A61K31/38 ,  A61K31/381 ,  A61K31/44 ,  A61K31/443 ,  A61P1/00 ,  A61P9/00 ,  A61P9/08 ,  A61P9/10 ,  A61P11/00 ,  A61P17/00 ,  A61P27/02 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P43/00 ,  C07C291/02 ,  C07D207/09 ,  C07D307/12 ,  C07D307/14 ,  C07D307/52 ,  C07D333/16 ,  C07D333/18 ,  C07D333/20 ,  C07D405/04 ,  C07D405/12 ,  C07D405/14 ,  C07D407/12 ,  C07D409/12 ,  C07D409/14 ,  C07D333/38 ,  C07C43/02 ,  C07D309/07

CPC分类号： C07D405/04 ,  C07D207/09 ,  C07D307/12 ,  C07D307/14 ,  C07D333/16 ,  C07D333/18 ,  C07D333/20 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  Y10S514/825 ,  Y10S514/826 ,  Y10S514/863 ,  Y10S514/912 ,  Y10S514/914 ,  Y10S514/921 ,  Y10S514/925

摘要： 2,5-Diaryl tetrahydrofurans, 2,5-diaryl tetrahydrothiophenes, 1,3-diaryl cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i,e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. Also disclosed is a method to treat disorders mediated by PAF and/or leukotrienes that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier, to a patient in need of such therapy.

摘要翻译： 公开了2,5-二芳基四氢呋喃，2,5-二芳基四氢噻吩，1,3-二芳基环戊烷，其减少趋化性和呼吸道爆发，导致在炎性或免疫反应期间形成多形核白细胞的有害氧自由基。 该化合物通过作为PAF受体拮抗剂，通过抑制酶5-脂氧合酶，或通过显示双重活性，即作为PAF受体拮抗剂和5-脂氧合酶抑制剂两者而表现出该生物学活性。 还公开了一种治疗由PAF和/或白三烯介导的病症的方法，其包括向有需要的患者施用有效量的一种或多种上述化合物或其药学上可接受的盐，任选地在药学上可接受的载体中 的这种疗法。

公开(公告)号：US06894059B1

公开(公告)日：2005-05-17

申请号：US09937667

申请日：2000-03-23

申请人： Ralph Scannell ,  Pierre Chatelain ,  Anna Toy-Palmer ,  Edmund Differding ,  James Ellis ,  Marie-Agnes Lassoie ,  Michelle Young ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  Timothy Lewis

发明人： Ralph Scannell ,  Pierre Chatelain ,  Anna Toy-Palmer ,  Edmund Differding ,  James Ellis ,  Marie-Agnes Lassoie ,  Michelle Young ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  Timothy Lewis

IPC分类号： C07D295/084 ,  C07D295/088 ,  C07D295/092 ,  C07D295/096 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/15 ,  C07D307/52 ,  A61K31/44 ,  A61K31/445

CPC分类号： C07D295/096 ,  C07D295/084 ,  C07D295/088 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/15 ,  C07D307/52

摘要： The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl piperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferably asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obsructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof.

摘要翻译： 本发明提供了1,4取代的哌嗪，1,4-取代的哌啶和1-取代的4-亚烷基哌啶化合物。 本发明的化合物是具有白细胞三烯抑制性质以及抗组胺能性质的双作用分子。 本发明的化合物可用于治疗可能存在组胺和/或白三烯组分的病症。 这些病症优选包括哮喘，季节性和常年性过敏性鼻炎，窦炎，结膜炎，食物过敏，鲭鱼中毒，牛皮癣，荨麻疹，瘙痒，湿疹，类风湿性关节炎，炎性肠病，慢性损伤性肺病，血栓性疾病和中耳炎。 还提供了通过向有需要的受试者施用有效的哮喘和减轻炎症的量的化合物来治疗哮喘和鼻炎的方法。

公开(公告)号：US06451801B1

公开(公告)日：2002-09-17

申请号：US09534947

申请日：2000-03-24

申请人： Ralph Scannell ,  Pierre Chatelain ,  Anna Toy-Palmer ,  Edmond Differding ,  James Ellis ,  Marie-Agnes Lassoie ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  Timothy Lewis

发明人： Ralph Scannell ,  Pierre Chatelain ,  Anna Toy-Palmer ,  Edmond Differding ,  James Ellis ,  Marie-Agnes Lassoie ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  Timothy Lewis

IPC分类号： A61K31495

CPC分类号： C07D295/096 ,  C07D295/084 ,  C07D295/088 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/15 ,  C07D307/14 ,  C07D307/52 ,  C07D401/04

摘要： The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl peperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferable asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof.

摘要翻译： 本发明提供了1,4取代的哌嗪，1,4-取代的哌啶和1-取代的4-亚烷基哌啶化合物。 本发明的化合物是具有白细胞三烯抑制性质以及抗组胺能性质的双作用分子。 本发明的化合物可用于治疗可能存在组胺和/或白三烯组分的病症。 这些病症包括优选的哮喘，季节性和常年性变态反应性鼻炎，窦炎，结膜炎，食物过敏，偶发性中毒，牛皮癣，荨麻疹，瘙痒，湿疹，类风湿性关节炎，炎性肠病，慢性阻塞性肺病，血栓性疾病和中耳炎。 还提供了通过向有需要的受试者施用有效的哮喘和减轻炎症的量的化合物来治疗哮喘和鼻炎的方法。

公开(公告)号：US5780503A

公开(公告)日：1998-07-14

申请号：US474444

申请日：1995-06-07

申请人： Tesfaye Biftu ,  Ralph Scannell ,  Xiong Cai ,  Sajjat Hussoin

发明人： Tesfaye Biftu ,  Ralph Scannell ,  Xiong Cai ,  Sajjat Hussoin

IPC分类号： C07D307/14 ,  C07D471/04 ,  A61K31/34 ,  A61K31/38 ,  A61K31/44 ,  A61K31/47

CPC分类号： C07D471/04 ,  C07D307/14

摘要： Disubstituted tetrahydrofurans, tetrahydrothiophenes, pyrrolidines and cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i. e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. A method to treat disorders mediated by PAF and/or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

公开(公告)号：US5792776A

公开(公告)日：1998-08-11

申请号：US265656

申请日：1994-06-27

申请人： Tesfaye Biftu ,  Ralph Scannell ,  Xiong Cai ,  Sajjat Hussoin

发明人： Tesfaye Biftu ,  Ralph Scannell ,  Xiong Cai ,  Sajjat Hussoin

IPC分类号： C07D307/14 ,  C07D471/04 ,  A61K31/44 ,  A61K31/40 ,  C07C233/00 ,  C07D307/02

CPC分类号： C07D471/04 ,  C07D307/14

摘要： Disubstituted tetrahydrofurans, tetrahydrothiophenes, pyrrolidines and cyclopentanes are disclosed that reduce the chemotaxis and respiratory burst leading to the formation of damaging oxygen radicals of polymorphonuclear leukocytes during an inflammatory or immune response. The compounds exhibit this biological activity by acting as PAF receptor antagonists, by inhibiting the enzyme 5-lipoxygenase, or by exhibiting dual activity, i. e., by acting as both a PAF receptor antagonist and inhibitor of 5-lipoxygenase. A method to treat disorders mediated by PAF and/or leukotrienes is also disclosed, that includes administering an effective amount of one or more of the above-identified compounds or a pharmaceutically acceptable salt thereof, optionally in a pharmaceutically acceptable carrier.

摘要翻译： 公开了二取代的四氢呋喃，四氢噻吩，吡咯烷和环戊烷，其减少趋化性和呼吸道爆发，导致在炎性或免疫反应期间形成多形核白细胞的有害氧自由基。 通过作为PAF受体拮抗剂，通过抑制酶5-脂氧合酶，或通过显示双重活性，化合物表现出这种生物学活性， 即作为PAF受体拮抗剂和5-脂肪氧合酶抑制剂。 还公开了治疗由PAF和/或白三烯介导的病症的方法，其包括任选地在药学上可接受的载体中施用有效量的一种或多种上述化合物或其药学上可接受的盐。

公开(公告)号：US06797713B2

公开(公告)日：2004-09-28

申请号：US10242346

申请日：2002-09-12

申请人： Ralph Scannell ,  Pierre Chatelain ,  Anna Toy-Palmer ,  Edmond Differding ,  James Ellis ,  Marie-Agnes Lassoie ,  Michelle Young ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  Timothy Lewis

发明人： Ralph Scannell ,  Pierre Chatelain ,  Anna Toy-Palmer ,  Edmond Differding ,  James Ellis ,  Marie-Agnes Lassoie ,  Michelle Young ,  Xiong Cai ,  Sajjat Hussoin ,  Gurmit Grewal ,  Timothy Lewis

IPC分类号： A61K31495

CPC分类号： C07D295/096 ,  C07D295/084 ,  C07D295/088 ,  C07D295/125 ,  C07D295/13 ,  C07D295/135 ,  C07D295/15 ,  C07D307/14 ,  C07D307/52 ,  C07D401/04

摘要： The present invention provides 1,4 substituted piperazines, 1,4 substituted piperidines, and 1-substituted, 4-alkylidenyl piperidines compounds. The compounds of the invention are dual acting molecules having both leukotriene inhibition properties as well as antihistaminergic properties. The compounds of the invention are useful for treating conditions in which there is likely to be a histamine and/or leukotriene component. These conditions include preferably asthma, seasonal and perennial allergic rhinitis, sinusitus, conjunctivitis, food allergy, scombroid poisoning, psoriasis, urticaria, pruritus, eczema, rheumatoid arthritis, inflammatory bowel disease, chronic obstructive pulmonary disease, thrombotic disease and otitis media. Also provided are methods of treating asthma and rhinitis by administering an effective asthma and rhinitis-relieving amount of the compounds to a subject in need thereof.

摘要翻译： 本发明提供了1,4取代的哌嗪，1,4-取代的哌啶和1-取代的4-亚烷基哌啶化合物。 本发明的化合物是具有白细胞三烯抑制性质以及抗组胺能性质的双作用分子。 本发明的化合物可用于治疗可能存在组胺和/或白三烯组分的病症。 这些病症优选包括哮喘，季节性和常年性过敏性鼻炎，鼻窦炎，结膜炎，食物过敏症，偶发性中毒，牛皮癣，荨麻疹，瘙痒，湿疹，类风湿性关节炎，炎性肠病，慢性阻塞性肺病，血栓性疾病和中耳炎。 还提供了通过向有需要的受试者施用有效的哮喘和减轻炎症的量的化合物来治疗哮喘和鼻炎的方法。