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1. 发明申请

US20080132553A1 Preventing and reversing the formation of advance glycosylation endproducts 审中-公开
标题翻译：预防和逆转先进的糖基化终产物的形成
公开(公告)号：US20080132553A1
公开(公告)日：2008-06-05
申请号：US12004614
申请日：2007-12-21
申请人： Anthony Cerami , Peter C. Ulrich , Dilip R. Wagle , San-Bao Hwang , Sara Vasan , John J. Egan
发明人： Anthony Cerami , Peter C. Ulrich , Dilip R. Wagle , San-Bao Hwang , Sara Vasan , John J. Egan
IPC分类号： A61K31/428 , A61K31/426 , A61P3/10 , A61P7/00 , A61P19/02
CPC分类号： G01N33/6842 , A61K8/49 , A61K31/425 , A61K31/426 , A61K31/428 , A61Q11/00 , A61Q19/00 , A61Q19/08 , C07D277/22 , C07D277/40 , G01N33/68 , G01N33/6854 , G01N2500/02
摘要： The present invention relates to methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain useful agents are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.
摘要翻译：本发明涉及抑制和逆转非酶交联（蛋白质老化）的方法。因此，公开了包含能够抑制靶蛋白的高级糖基化终产物形成的试剂的组合物，并且还通过切割高级糖基化终产物中存在的基于α-二羰基的蛋白质交联来进一步反转高级糖基化终产物中的预形成交联。某些有用的试剂是噻唑鎓盐。该方法包括使靶蛋白与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。还公开了用于检测非酶交联反转的新型免疫测定。

2. 发明授权

US07022719B2 Preventing and reversing the formation of advance glycosylation endproducts 失效
标题翻译：预防和逆转先进的糖基化终产物的形成
公开(公告)号：US07022719B2
公开(公告)日：2006-04-04
申请号：US10418398
申请日：2003-04-18
申请人： Anthony Cerami , Peter C. Ulrich , Dilip R. Wagle , San-Bao Hwang , Sara Vasan , John J. Egan
发明人： Anthony Cerami , Peter C. Ulrich , Dilip R. Wagle , San-Bao Hwang , Sara Vasan , John J. Egan
IPC分类号： A61K31/426 , C07D277/20
CPC分类号： G01N33/6842 , A61K8/49 , A61K31/425 , A61K31/426 , A61K31/428 , A61Q11/00 , A61Q19/00 , A61Q19/08 , C07D277/22 , C07D277/40 , G01N33/68 , G01N33/6854 , G01N2500/02
摘要： The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain useful agents are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A novel immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.
摘要翻译：本发明涉及用于抑制和逆转非酶交联（蛋白质老化）的组合物和方法。因此，公开了包含能够抑制靶蛋白的高级糖基化终产物形成的试剂的组合物，并且还通过切割高级糖基化终产物中存在的基于α-二羰基的蛋白质交联来进一步反转高级糖基化终产物中的预形成交联。某些有用的试剂是噻唑鎓盐。该方法包括使靶蛋白与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。还公开了用于检测非酶交联反转的新型免疫测定。

3. 发明授权

US06319934B1 Reversing advanced glycosylation cross-links using heterocyclic-substituted thiazolium compounds 失效
标题翻译：使用杂环取代的噻唑化合物逆转先进的糖基化交联
公开(公告)号：US06319934B1
公开(公告)日：2001-11-20
申请号：US09644024
申请日：2000-08-23
申请人： Dilip R. Wagle , Sheng-Ding Fang , Taikyun Rho , John J. Egan , Sara Vasan , Peter Ulrich , Anthony Cerami
发明人： Dilip R. Wagle , Sheng-Ding Fang , Taikyun Rho , John J. Egan , Sara Vasan , Peter Ulrich , Anthony Cerami
IPC分类号： C07D27724
CPC分类号： C07D277/22 , A61K31/427 , A61K31/4439 , A61K31/454 , A61K31/4709 , A61K31/496 , A61K31/5355 , A61K31/541 , A61K31/55 , C07D277/44 , C07D417/06
摘要： The present invention relates to compositions and methods for reversing advanced glycosylation end product-mediated cross-linking and protein aging. Accordingly, compositions are described which comprise thiazolium compounds substituted with heterocyclic groups which are capable of reversing the formation of advanced glycosylation end product cross-links. Both industrial and therapeutic applications for the invention are disclosed, as food spoilage and animal protein aging can be treated. Such compounds have particular application in the treatment of protein aging such as is responsible for the complications of aging and diabetes.
摘要翻译：本发明涉及用于逆转晚期糖基化终产物介导的交联和蛋白质老化的组合物和方法。因此，描述了包含被能够逆转高级糖基化终产物交联的形成的杂环基取代的噻唑鎓化合物的组合物。公开了用于本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。这些化合物在治疗老化和糖尿病并发症等蛋白质老化中具有特殊的应用。

4. 发明授权

US5661139A Bis-(2-aryl) hydrazones 失效
标题翻译：双 - （2-芳基）腙
公开(公告)号：US5661139A
公开(公告)日：1997-08-26
申请号：US485387
申请日：1995-06-07
申请人： Michael E. Lankin , David H. Shih , Dilip R. Wagle , San-Bao Hwang
发明人： Michael E. Lankin , David H. Shih , Dilip R. Wagle , San-Bao Hwang
IPC分类号： C07C251/76 , C07C251/86 , C07C281/18 , C07D213/53 , C07D213/77 , C07D233/52 , C07D233/88 , C07D239/18 , C07D249/04 , C07D249/08 , C07D333/22 , C07D401/14 , C07D405/14 , C07D409/14 , C07F9/09 , A61K31/66 , C07C241/00 , C07D211/72
CPC分类号： C07D213/77 , C07C251/76 , C07C251/86 , C07C281/18 , C07D213/53 , C07D233/52 , C07D239/18 , C07D249/04 , C07D333/22 , C07D401/14 , C07D405/14 , C07D409/14 , C07F9/096
摘要： The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises a bis-(2-aryl)hydrazone capable of inhibiting the formation of advanced glycosylation endproducts of target proteins. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
摘要翻译：本发明涉及抑制非酶交联（蛋白质老化）的组合物和方法。因此，公开了一种组合物，其包含能够抑制靶蛋白的高级糖基化终产物形成的双 - （2-芳基）腙。该方法包括使靶蛋白与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。

5. 发明授权

US5500439A Aminopyrazoles 失效
标题翻译：氨基吡唑
公开(公告)号：US5500439A
公开(公告)日：1996-03-19
申请号：US164466
申请日：1993-12-09
申请人： Peter C. Ulrich , Dilip R. Wagle
发明人： Peter C. Ulrich , Dilip R. Wagle
IPC分类号： A61K31/415
CPC分类号： A61K31/415
摘要： The present invention relates to compounds, compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, a composition is disclosed which comprises aminopyrazoles capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of an early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
摘要翻译：本发明涉及抑制非酶交联（蛋白质老化）的化合物，组合物和方法。因此，公开了一种组合物，其包含氨基吡唑，其能够通过与通过其初始糖基化形成的这种靶蛋白的早期糖基化产物的羰基部分反应来抑制靶蛋白的晚期糖基化终产物的形成。该方法包括使靶蛋白与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。

6. 发明授权

US5326779A Method of inhibiting the advanced glycosylation of proteins using 1,2-disubstituted-benzimidazoles 失效
标题翻译：使用1,2-二取代 - 苯并咪唑抑制蛋白质高级糖基化的方法
公开(公告)号：US5326779A
公开(公告)日：1994-07-05
申请号：US986673
申请日：1992-12-08
申请人： Peter C. Ulrich , Anthony Cerami , Dilip R. Wagle
发明人： Peter C. Ulrich , Anthony Cerami , Dilip R. Wagle
IPC分类号： A61K8/49 , A61K31/155 , A61K31/195 , A61K31/40 , A61K31/415 , A61K31/4178 , A61K31/44 , A61K31/445 , A61K31/495 , A61K31/535 , A61K31/55 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/08 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/68
CPC分类号： G01N33/6842 , A61K31/155 , A61K31/195 , A61K31/40 , A61K31/415 , A61K31/4178 , A61K31/44 , A61K31/445 , A61K31/495 , A61K31/535 , A61K31/55 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61K8/4946 , A61Q11/00 , A61Q19/08 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/68 , G01N33/6893 , A61K2039/6081 , G01N2333/922
摘要： The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging). Accordingly, composition is disclosed which comprises 1,2-disubstituted benzimidazoles capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
摘要翻译：本发明涉及抑制非酶交联（蛋白质老化）的组合物和方法。因此，公开了包含能够通过其初始糖基化形成的这种靶蛋白的早期糖基化产物的羰基部分反应来抑制靶蛋白的晚期糖基化终产物形成的1,2-二取代苯并咪唑的组合物。该方法包括使靶蛋白与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。

7. 发明授权

US5358960A Method for inhibiting advanced glycosylation of proteins using aminosubstituted imidazoles 失效
标题翻译：使用氨基取代咪唑抑制蛋白质晚期糖基化的方法
公开(公告)号：US5358960A
公开(公告)日：1994-10-25
申请号：US986662
申请日：1992-12-08
申请人： Peter Ulrich , Anthony Cerami , Dilip R. Wagle
发明人： Peter Ulrich , Anthony Cerami , Dilip R. Wagle
IPC分类号： A61K8/43 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/08 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/58 , G01N33/68
CPC分类号： A61K8/43 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61Q19/08 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/582 , G01N33/68 , G01N33/6842 , G01N33/6893 , A61K2039/6081 , G01N2333/922 , Y10S514/866
摘要： The present invention relates to compositions and methods for inhibiting nonenzymatic cross-linking (protein aging), Accordingly, a composition is disclosed which comprises 2-aminoimidazoles capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation, The method comprises contacting the target protein with the composition, Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
摘要翻译：本发明涉及抑制非酶交联（蛋白质老化）的组合物和方法。因此，公开了一种组合物，其包含2-氨基咪唑，其能够通过与靶蛋白的羰基部分反应来抑制靶蛋白的高级糖基化终产物的形成通过其初始糖基化形成的这种靶蛋白的早期糖基化产物。该方法包括使靶蛋白与组合物接触。本发明的工业和治疗应用都是可以想象的，因为可以处理食物腐败和动物蛋白质老化。

8. 发明授权

US5221683A Diaminopyridine compounds and methods of use 失效
标题翻译：二氨基吡啶化合物和使用方法
公开(公告)号：US5221683A
公开(公告)日：1993-06-22
申请号：US822310
申请日：1992-01-17
申请人： Peter C. Ulrich , Anthony Cerami , Dilip R. Wagle
发明人： Peter C. Ulrich , Anthony Cerami , Dilip R. Wagle
IPC分类号： A61K8/43 , A61K8/49 , A61K31/15 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K31/44 , A61K31/495 , A61K31/535 , A61K38/19 , A61K38/20 , A61K38/21 , A61K38/38 , A61K39/00 , A61Q11/00 , A61Q19/00 , A61Q19/08 , C07D233/02 , C07D239/04 , C07D243/04 , C07D295/215 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/58 , G01N33/68
CPC分类号： G01N33/6842 , A61K31/15 , A61K31/155 , A61K31/195 , A61K31/415 , A61K31/4178 , A61K31/44 , A61K31/495 , A61K31/535 , A61K38/191 , A61K38/2006 , A61K38/217 , A61K38/38 , A61K39/0005 , A61K8/43 , A61K8/4926 , A61Q11/00 , A61Q19/00 , A61Q19/08 , C07D233/02 , C07D239/04 , C07D243/04 , C07D295/215 , C07D405/14 , C07K16/28 , G01N33/533 , G01N33/573 , G01N33/582 , G01N33/68 , G01N33/6893 , A61K2039/6081 , G01N2333/922
摘要： The present invention relates to compositions and method for inhibiting nonenzymatic cross-linking (protein aging) which contain diaminopyridines and derivates thereof. Accordingly, a composition is disclosed which comprises an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins by reacting with the carbonyl moiety of the early glycosylation product of such target proteins formed by their initial glycosylation. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated.
摘要翻译：本发明涉及抑制含有二氨基吡啶及其衍生物的非酶交联（蛋白质老化）的组合物和方法。因此，公开了一种组合物，其包含能够通过与通过其初始糖基化形成的这些靶蛋白的早期糖基化产物的羰基部分反应来抑制靶蛋白的高级糖基化终产物的形成的试剂。该方法包括使靶蛋白与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。

9. 发明授权

US06440749B1 Method of treating certain indications associated with hyperglycemia 失效
标题翻译：治疗与高血糖相关的某些适应症的方法
公开(公告)号：US06440749B1
公开(公告)日：2002-08-27
申请号：US09470482
申请日：1999-12-22
申请人： Anthony Cerami , Peter C. Ulrich , Dilip R. Wagle , San-Bao Hwang , Sara Vasan , John J. Egan
发明人： Anthony Cerami , Peter C. Ulrich , Dilip R. Wagle , San-Bao Hwang , Sara Vasan , John J. Egan
IPC分类号： C07D27762
CPC分类号： G01N33/6842 , A61K8/49 , A61K31/425 , A61K31/426 , A61K31/428 , A61Q11/00 , A61Q19/00 , A61Q19/08 , C07D277/22 , C07D277/40 , G01N33/68 , G01N33/6854 , G01N2500/02
摘要： The present invention relates to compositions and methods for inhibiting and reversing nonenzymatic cross-linking (protein aging). Accordingly, compositions are disclosed which comprise an agent capable of inhibiting the formation of advanced glycosylation endproducts of target proteins, and which additionally reverse pre-formed crosslinks in the advanced glycosylation endproducts by cleaving alpha-dicarbonyl-based protein crosslinks present in the advanced glycosylation endproducts. Certain agents useful are thiazolium salts. The method comprises contacting the target protein with the composition. Both industrial and therapeutic applications for the invention are envisioned, as food spoilage and animal protein aging can be treated. A immunoassay for detection of the reversal of the nonenzymatic crosslinking is also disclosed.
摘要翻译：本发明涉及用于抑制和逆转非酶交联（蛋白质老化）的组合物和方法。因此，公开了包含能够抑制靶蛋白的高级糖基化终产物形成的试剂的组合物，并且还通过切割高级糖基化终产物中存在的基于α-二羰基的蛋白质交联来进一步反转高级糖基化终产物中的预形成交联。有用的某些试剂是噻唑鎓盐。该方法包括使靶蛋白与组合物接触。预想到本发明的工业和治疗应用，因为可以处理食物腐败和动物蛋白质老化。还公开了用于检测非酶交联反转的免疫测定。

10. 发明授权

US06326396B1 Glucose and lipid lowering compounds 失效
标题翻译：葡萄糖和降脂化合物
公开(公告)号：US06326396B1
公开(公告)日：2001-12-04
申请号：US09439706
申请日：1999-11-12
申请人： Dilip R. Wagle , Sheng Ding Fang , Ihor Terleckyj , John Resek , John J. Egan
发明人： Dilip R. Wagle , Sheng Ding Fang , Ihor Terleckyj , John Resek , John J. Egan
IPC分类号： A61K3134
CPC分类号： A61K31/34
摘要： Provided are, among other things, lipid-lowering or glucose-lowering methods and compounds, particularly lipid-lowering or glucose-lowering compounds, with an A-B ring structure as follows: wherein the dotted line between carbons 5 and 6, the dotted line between carbon 4 and R2, and the dotted line between carbon 11 and R3 each independently represent an optional double bond from the respective numbered carbon to a linked carbon, and wherein X is hydroxy or, together with Y is oxy linking carbon 8 and carbon 12.
摘要翻译：尤其提供具有如下的AB环结构的降脂或葡萄糖降低方法和化合物，特别是降脂或葡萄糖降低化合物，其中碳5和6之间的虚线是虚线碳4和R 2之间的虚线，碳11和R 3之间的虚线各自独立地表示从相应的编号的碳到连接的碳的任选的双键，并且其中X是羟基，或者与Y一起是氧连接碳8和碳12。

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