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：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：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：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：US20150011590A1

公开(公告)日：2015-01-08

申请号：US14376787

申请日：2013-02-12

申请人： Ann E. WEBER ,  Tesfaye BIFTU ,  Merck Sharp & Dohme Corporation

发明人： Ann E. Weber ,  Tesfaye Biftu

IPC分类号： C07D487/04 ,  A61K31/155 ,  A61K31/4439 ,  A61K31/4162

CPC分类号： C07D487/04 ,  A61K31/155 ,  A61K31/4162 ,  A61K31/4439 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention is directed to novel substituted dihydropyrrolopyrazoles of structural Formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及结构式I的新型取代二氢吡咯并吡唑，其是二肽基肽酶-IV酶的抑制剂，其可用于治疗或预防涉及二肽基肽酶-IV酶的疾病，例如糖尿病，特别是 2型糖尿病 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。

公开(公告)号：US20130203786A1

公开(公告)日：2013-08-08

申请号：US13643121

申请日：2011-05-16

申请人： Jacqueline D. Hicks ,  Tesfaye Biftu ,  Ping Chen ,  Xiaoxia Qian ,  Robert R. Wilkening

发明人： Jacqueline D. Hicks ,  Tesfaye Biftu ,  Ping Chen ,  Xiaoxia Qian ,  Robert R. Wilkening

IPC分类号： C07D487/04 ,  A61K31/506 ,  A61K45/06 ,  A61K31/519 ,  A61K31/437 ,  A61K31/4162 ,  A61K31/4439

CPC分类号： C07D487/04 ,  A61K31/4162 ,  A61K31/437 ,  A61K31/4439 ,  A61K31/506 ,  A61K31/519 ,  A61K45/06 ,  C07D471/04

摘要： The present invention is directed to novel amino-substituted seven-membered heterocyclic compounds of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

摘要翻译： 本发明涉及结构式（I）的新型氨基取代的七元杂环化合物，其为二肽基肽酶-IV酶的抑制剂，其可用于治疗或预防其中二肽基肽酶-IV酶 涉及糖尿病，特别是2型糖尿病。 本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的用途。

公开(公告)号：US20130123237A1

公开(公告)日：2013-05-16

申请号：US13812536

申请日：2012-02-23

申请人： Rajan Anand ,  James M. Apgar ,  Tesfaye Biftu ,  Ping Chen ,  Lin Chu ,  Vincent J. Colandrea ,  Guizhen Dong ,  James F. Dropinski ,  Danqing Feng ,  Jacqueline D. Hicks ,  Jinlong Jiang ,  Alexander J. Kim ,  Kenneth J. Leavitt ,  Bing Li ,  Xiaoxia Qian ,  Iyassu Sebhat ,  Lan Wei ,  Robert R. Wilkening ,  Zhicai Wu

发明人： Rajan Anand ,  James M. Apgar ,  Tesfaye Biftu ,  Ping Chen ,  Lin Chu ,  Vincent J. Colandrea ,  Guizhen Dong ,  James F. Dropinski ,  Danqing Feng ,  Jacqueline D. Hicks ,  Jinlong Jiang ,  Alexander J. Kim ,  Kenneth J. Leavitt ,  Bing Li ,  Xiaoxia Qian ,  Iyassu Sebhat ,  Lan Wei ,  Robert R. Wilkening ,  Zhicai Wu

IPC分类号： A61K31/5377 ,  A61K31/437 ,  A61K31/4985 ,  A61K31/351 ,  A61K31/397 ,  A61K31/4412 ,  C07D471/04 ,  A61K31/496

CPC分类号： A61K31/5377 ,  A61K31/351 ,  A61K31/366 ,  A61K31/397 ,  A61K31/437 ,  A61K31/4412 ,  A61K31/496 ,  A61K31/4985 ,  A61K31/519 ,  A61K45/06 ,  C07D471/04 ,  C07D519/00 ,  A61K2300/00

摘要： Novel compounds of structural formula (I) are activators of AMP-protein kinase and are useful in the treatment, prevention and suppression of diseases mediated by the AMPK-activated protein kinase. The compounds of the present invention are useful in the treatment of Type 2 diabetes, hyperglycemia, metabolic syndrome, obesity, hypercholesterolemia, and hypertension.

摘要翻译： 结构式（I）的新型化合物是AMP-蛋白激酶的活化剂，可用于治疗，预防和抑制由AMPK激活的蛋白激酶介导的疾病。 本发明的化合物可用于治疗2型糖尿病，高血糖症，代谢综合征，肥胖症，高胆固醇血症和高血压。