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1. 发明授权

US5721356A Orally active adenosine kinase inhibitors 失效
标题翻译：口服活性腺苷激酶抑制剂
公开(公告)号：US5721356A
公开(公告)日：1998-02-24
申请号：US473491
申请日：1995-06-07
申请人： Bheemarao G. Ugarkar , Mark D. Erion , Jorge E. Gomez Galeno , Angelo J. Castellino , Clinton E. Browne
发明人： Bheemarao G. Ugarkar , Mark D. Erion , Jorge E. Gomez Galeno , Angelo J. Castellino , Clinton E. Browne
IPC分类号： C12N9/99 , A61K31/00 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61P25/04 , A61P25/08 , A61P29/00 , A61P43/00 , C07D487/04 , C07D519/00 , C07H19/04 , C07H19/052 , C07H19/06 , C07H19/14 , C07H19/16 , C07H19/23
CPC分类号： C07H19/04 , A61K31/00 , A61K31/7064 , A61K31/7076 , C07D487/04 , C07H19/052 , C07H19/06 , C07H19/14 , C07H19/16
摘要： This invention relates to adenosine kinase inhibitors and to nucleoside analogs, specifically to orally active, substituted 5-aryl pyrrolo�2,3-d!pyrimidine and 3-aryl pyrazolo�3,4-d! pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention also relates to the preparation and use of these and other adenosine kinase inhibitors in the treatment of cardiovascular and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.
摘要翻译：本发明涉及腺苷激酶抑制剂和核苷类似物，特别是具有作为腺苷激酶活性的口服活性的取代的5-芳基吡咯并[2,3-d]嘧啶和3-芳基吡唑并[3,4-d]嘧啶核苷类似物抑制剂。本发明还涉及这些和其它腺苷激酶抑制剂在治疗心血管和脑血管疾病，炎症等疾病中的制备和应用，可以通过增加腺苷的局部浓度来调节。

2. 发明授权

US5573772A Methods for protecting tissues and organs from ischemic damage 失效
标题翻译：保护组织和器官免受缺血损伤的方法
公开(公告)号：US5573772A
公开(公告)日：1996-11-12
申请号：US214942
申请日：1994-03-17
申请人： James M. Downey , Kevin M. Mullane
发明人： James M. Downey , Kevin M. Mullane
IPC分类号： A61F2/02 , A61K9/14 , A61K9/20 , A61K9/48 , A61M31/00 , C07H20060101
CPC分类号： A61K31/70 , Y10S514/936
摘要： Methods for protecting tissues and organs including the heart central nervous system, and kidney from ischemic damage are described and claimed based upon the recognition that protection against infarction is mediated by A3 rather than A1 adenosine receptors, as was previously thought, and that the receptor mediating protection in other organs and tissues has not been defined. Methods for selectively stimulating A3 adenosine receptors are described and claimed, as such selection is shown to prevent or substantially reduce cell death resulting from ischemia with or without reperfusion in humans. According to this invention, the A3 adenosine receptor is selectively stimulated by administering a compound which is an A3 adenosine receptor-selective agonist. Prevention of tissue death is also achieved by administering a compound which is a non-selective adenosine receptor agonist together with compounds that act as antagonists to the A1 and A2 adenosine receptor.
摘要翻译：基于以前认为由APC而不是A1腺苷受体介导的对梗塞的保护的认识描述和要求保护包括心脏中枢神经系统在内的组织和器官以及来自缺血性损伤的肾脏的方法，并且受体介导其他器官和组织的保护尚未定义。描述和要求保护选择性刺激A3腺苷受体的方法，因为这样的选择被证明可预防或显着减少由于在人或不伴有再灌注的局部缺血导致的细胞死亡。根据本发明，通过给予作为A3腺苷受体选择性激动剂的化合物来选择性地刺激A3腺苷受体。还通过将作为非选择性腺苷受体激动剂的化合物与作为Aβ和腺苷受体的拮抗剂的化合物一起施用来预防组织死亡。

3. 发明授权

US5506347A Lyxofuranosyl analogues of adenosine 失效
标题翻译：腺苷的Lyxofuranosyl类似物
公开(公告)号：US5506347A
公开(公告)日：1996-04-09
申请号：US191282
申请日：1994-02-03
申请人： Mark D. Erion , Bheemarao G. Ugarkar , Angelo J. Castellino
发明人： Mark D. Erion , Bheemarao G. Ugarkar , Angelo J. Castellino
IPC分类号： C07D473/40 , A61K31/505 , A61K31/52 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7076 , A61P7/02 , A61P9/00 , A61P25/00 , A61P29/00 , A61P43/00 , C07D487/04 , C07H19/04 , C07H19/06 , C07H19/14 , C07H19/16 , C07G3/00
CPC分类号： C07H19/04 , C07H19/06 , C07H19/14 , C07H19/16
摘要： Novel lyxose derivatives which selectively inhibit adenosine kinase and methods of preparing these compounds are provided. These compounds are useful in treating certain conditions in vivo which may be ameliorated by increased local concentrations of adenosine.
摘要翻译：提供了选择性抑制腺苷激酶的新型赖索糖衍生物和制备这些化合物的方法。这些化合物可用于治疗体内某些条件，这可以通过增加局部腺苷浓度而改善。

4. 发明授权

US5775329A Method and compounds for diagnosing coronary artery disease 失效
标题翻译：用于诊断冠状动脉疾病的方法和化合物
公开(公告)号：US5775329A
公开(公告)日：1998-07-07
申请号：US482435
申请日：1995-06-07
申请人： Ernest K. Metzner , Mark D. Erion
发明人： Ernest K. Metzner , Mark D. Erion
IPC分类号： C07C217/02 , C07C247/04 , C07C255/24 , C07C317/28 , C07C323/25 , A61B5/02 , A61B19/00 , A61K31/72 , C07C255/08
CPC分类号： C07C323/25 , C07C217/02 , C07C247/04 , C07C255/24 , C07C317/28
摘要： The present invention relates generally to methods of diagnosis, evaluation and treatment of coronary artery disease in mammals using substituted catecholamines and compounds therefore. It also relates to the preparation, use and administration of these compounds which are useful in the diagnosis, evaluation and treatment of coronary artery disease by means of a feedback controlled drug delivery system that delivers exercise simulating agents which are capable of eliciting acute responses similar to those elicited by aerobic exercise.
摘要翻译：本发明一般涉及使用取代的儿茶酚胺和化合物的哺乳动物的冠状动脉疾病的诊断，评估和治疗方法。它还涉及这些化合物的制备，使用和给药，其可用于通过反馈控制的药物递送系统诊断，评估和治疗冠状动脉疾病，所述反馈控制药物递送系统提供能够引起类似于那些由有氧运动引起的。

5. 发明授权

US5674998A C-4' modified adenosine kinase inhibitors 失效
标题翻译： C-4'修饰的腺苷激酶抑制剂
公开(公告)号：US5674998A
公开(公告)日：1997-10-07
申请号：US486161
申请日：1995-06-07
申请人： Serge H. Boyer , Mark D. Erion , Bheemarao G. Ugarkar
发明人： Serge H. Boyer , Mark D. Erion , Bheemarao G. Ugarkar
IPC分类号： C12N9/99 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61P17/00 , A61P25/08 , A61P29/00 , A61P43/00 , C07H19/04 , C07H19/044 , C07H19/06 , C07H19/14 , C07H19/23
CPC分类号： C07H19/04 , C07H19/06 , C07H19/14
摘要： This invention relates to adenosine kinase inhibitors and to nucleoside analogs, C-4' modified pyrrolo�2,3-d!pyrimidine and pyrazolo�3,4-d!pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention relates to nucleoside analogs of this kind, having zero substitutions or two substitutions at the C-4' position of the furanose (sugar) moiety. The invention also relates to the preparation and use of these adenosine kinase inhibitors in the treatment of cardiovascular, and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.
摘要翻译：本发明涉及具有作为腺苷激酶抑制剂活性的腺苷激酶抑制剂和核苷类似物C-4'修饰的吡咯并[2,3-d]嘧啶和吡唑并[3,4-d]嘧啶核苷类似物。本发明涉及这样的核苷类似物，其在呋喃糖（糖）部分的C-4'位置具有零取代或两个取代。本发明还涉及这些腺苷激酶抑制剂在治疗心血管和脑血管疾病，炎症等疾病中的制备和应用，可以通过增加腺苷的局部浓度来调节。

6. 发明授权

US5646128A Methods for treating adenosine kinase related conditions 失效
标题翻译：治疗腺苷激酶相关病症的方法
公开(公告)号：US5646128A
公开(公告)日：1997-07-08
申请号：US349125
申请日：1994-12-01
申请人： Gary S. Firestein , Bheemarao G. Ugarkar , Leonard P. Miller , Harry E. Gruber , David A. Bullough , Mark D. Erion , Angelo J. Castellino , Clinton E. Browne
发明人： Gary S. Firestein , Bheemarao G. Ugarkar , Leonard P. Miller , Harry E. Gruber , David A. Bullough , Mark D. Erion , Angelo J. Castellino , Clinton E. Browne
IPC分类号： A61K31/00 , C07H19/04 , C07H19/052 , A61K31/70
CPC分类号： A61K31/7064 , A61K31/00 , A61K31/7076 , C07H19/04 , C07H19/052 , Y10S514/825 , Y10S514/885 , Y10S514/886
摘要： Novel compounds which selectively inhibit adenosine kinase and methods of preparing adenosine kinase inhibitors are provided. Also provided are methods of treating various inflammatory conditions, including arthritis and SIRS, which may be ameliorated by increased local concentrations of adenosine using adenosine kinase inhibitors.
摘要翻译：提供了选择性抑制腺苷激酶的新型化合物和制备腺苷激酶抑制剂的方法。还提供了治疗各种炎性病症（包括关节炎和SIRS）的方法，其可以通过使用腺苷激酶抑制剂增加腺苷浓度来改善。

7. 发明授权

US5726302A Water soluble adenosine kinase inhibitors 失效
标题翻译：水溶性腺苷激酶抑制剂
公开(公告)号：US5726302A
公开(公告)日：1998-03-10
申请号：US473492
申请日：1995-06-07
申请人： Bheemarao G. Ugarkar , Mark D. Erion , Jorge E. Gomez Galeno
发明人： Bheemarao G. Ugarkar , Mark D. Erion , Jorge E. Gomez Galeno
IPC分类号： A61K31/00 , A61K31/70 , A61K31/7042 , A61K31/7052 , A61K31/7064 , A61P25/04 , A61P25/08 , A61P29/00 , A61P43/00 , C07D487/04 , C07D519/00 , C07H19/04 , C07H19/052 , C07H19/06 , C07H19/14 , C07H19/16 , C07H19/23
CPC分类号： C07H19/04 , A61K31/00 , A61K31/7064 , A61K31/7076 , C07D487/04 , C07H19/052 , C07H19/06 , C07H19/14 , C07H19/16
摘要： This invention relates to adenosine kinase inhibitors and to nucleoside analogs, specifically to water soluble, aryl substituted 4-amino pyrrolo�2,3-d! pyrimidine and pyrazolo�3,4-d! pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention also relates to the preparation and use of these adenosine kinase inhibitors in the treatment of cardiovascular, and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.
摘要翻译：本发明涉及腺苷激酶抑制剂和核苷类似物，具体涉及具有作为腺苷激酶抑制剂活性的水溶性芳基取代的4-氨基吡咯并[2,3-d]嘧啶和吡唑并[3,4-d]嘧啶核苷类似物。本发明还涉及这些腺苷激酶抑制剂在治疗心血管和脑血管疾病，炎症等疾病中的制备和应用，可以通过增加腺苷的局部浓度来调节。

8. 发明授权

US5777100A AICA riboside analogs 失效
标题翻译： AICA核苷类似物
公开(公告)号：US5777100A
公开(公告)日：1998-07-07
申请号：US485665
申请日：1995-06-07
申请人： David A. Bullough , Harry E. Gruber , Ernest K. Metzker , Kevin M. Mullane , Bheemarao G. Ugarkar , Clinton E. Browne
发明人： David A. Bullough , Harry E. Gruber , Ernest K. Metzker , Kevin M. Mullane , Bheemarao G. Ugarkar , Clinton E. Browne
IPC分类号： C07H19/052 , A61K31/70
CPC分类号： C07H19/052
摘要： Analogs of 5-amino-1-beta-D-ribofuranosylimidazole-4-carboxamide (AICA riboside) are provided which are useful in increasing extracellular levels of adenosine.
摘要翻译：提供5-氨基-1-β-D-呋喃核糖基咪唑-4-甲酰胺（AICA riboside）的类似物，其可用于增加腺苷的细胞外水平。

9. 发明授权

US5460605A Diagnosis, evaluation and treatment of coronary artery disease by exercise simulation using closed loop drug delivery of an exercise simulating agent beta agonist 失效
标题翻译：通过使用运动模拟剂β激动剂的闭环药物递送的运动模拟来诊断，评估和治疗冠状动脉疾病
公开(公告)号：US5460605A
公开(公告)日：1995-10-24
申请号：US163839
申请日：1993-12-07
申请人： Ronald R. Tuttle , Clinton E. Browne
发明人： Ronald R. Tuttle , Clinton E. Browne
IPC分类号： A61B5/00 , A61B10/00 , A61K31/135 , A61K31/16 , A61K31/165 , A61M1/00 , A61M37/00 , A61N1/30 , A61N1/32 , A61P9/00 , A61P9/10 , A61P25/02 , C07C45/30 , C07C215/60 , C07C217/62 , C07C237/30 , A61M31/00
CPC分类号： C07C237/30 , A61K31/135 , A61K31/16 , A61N1/044 , A61N1/30 , A61N1/325 , C07C215/60 , C07C217/62 , C07C45/305 , A61N1/0448 , Y10S128/13
摘要： Methods and devices for the diagnosis, evaluation and treatment of coronary artery disease (CAD) by means of a closed-loop drug delivery system that delivers an exercise simulating agent, including novel exercise simulating agents which elicit both acute and adaptive cardiovascular responses similar to those elicited by aerobic activity are provided. The acute responses to the exercise simulating agent are used to diagnose and evaluate CAD in lieu of the acute responses to aerobic exercise. Due to their adaptive responses these compounds may be used to treat CAD in lieu of the adaptive responses caused by aerobic exercise training or to treat other conditions where the adaptive responses caused by aerobic exercise are desirable.
摘要翻译：用于通过递送运动模拟剂的闭环药物递送系统来诊断，评估和治疗冠状动脉疾病（CAD）的方法和装置，包括引起急性和适应性心血管反应的新型运动模拟剂，其类似于那些提供有氧活动引发的。对运动模拟剂的急性反应用于诊断和评估CAD，代替对有氧运动的急性反应。由于其适应性反应，这些化合物可用于治疗CAD以代替由有氧运动训练引起的适应性反应或治疗其中需要有氧运动引起的适应性反应的其他状况。

10. 发明授权

US5443836A Methods for protecting tissues and organs from ischemic damage 失效
标题翻译：保护组织和器官免受缺血损伤的方法
公开(公告)号：US5443836A
公开(公告)日：1995-08-22
申请号：US33310
申请日：1993-03-15
申请人： James M. Downey , Kevin Mullane
发明人： James M. Downey , Kevin Mullane
IPC分类号： A61F2/02 , A61K9/14 , A61K9/20 , A61K9/48 , A61M31/00 , C07H20060101
CPC分类号： A61K31/70 , Y10S514/936
摘要： Methods for protecting tissues and organs including the heart central nervous system, and kidney from ischemic damage are described and claimed based upon the recognition that protection against infarction is mediated by A3 rather than A1 adenosine receptors, as was previously thought, and that the receptor mediating protection in other organs and tissues has not been defined. Methods for selectively stimulating A3 adenosine receptors are described and claimed, as such selection is shown to prevent or substantially reduce cell death resulting from ischemia with or without reperfusion in humans. According to this invention, the A3 adenosine receptor is selectively stimulated by administering a compound which is an A3 adenosine receptor-selective agonist. Prevention of tissue death is also achieved by administering a compound which is a non-selective adenosine receptor agonist together with compounds that act as antagonists to the A1 and A2 adenosine receptors.
摘要翻译：基于以前认为由APC而不是A1腺苷受体介导的对梗塞的保护的认识描述和要求保护包括心脏中枢神经系统在内的组织和器官以及来自缺血性损伤的肾脏的方法，并且受体介导其他器官和组织的保护尚未定义。描述和要求保护选择性刺激A3腺苷受体的方法，因为这样的选择被证明可预防或显着减少由于在人或不伴有再灌注的局部缺血导致的细胞死亡。根据本发明，通过给予作为A3腺苷受体选择性激动剂的化合物来选择性地刺激A3腺苷受体。还通过将作为非选择性腺苷受体激动剂的化合物与作为Aβ和腺苷受体的拮抗剂的化合物一起施用来预防组织死亡。

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