公开(公告)号：US20070117765A1

公开(公告)日：2007-05-24

申请号：US11601714

申请日：2006-11-17

申请人： Anthony Sauve ,  Tianle Yang

发明人： Anthony Sauve ,  Tianle Yang

IPC分类号： A61K31/7052 ,  C07H19/048

CPC分类号： A61K31/706 ,  A61K31/351 ,  A61K45/06 ,  C07H1/00 ,  C07H19/048

摘要： The invention relates to compositions of nicotinoyl ribosides and nicotinamide riboside derivatives and their methods of use. In some embodiments, the invention relates to methods of making nicotinoyl ribosides. In some embodiments, the invention relates to pharmaceutical compositions and nutritional supplements containing a nicotinoyl riboside. In further embodiments, the invention relates to methods of using nicotinoyl ribosides and nicotinamide riboside derivatives that promote the increase of intracellular levels of nicotinamide adenine dinucleotide (NAD+) in cells and tissues for improving cell and tissue survival.

摘要翻译： 本发明涉及烟酰基核糖苷和烟酰胺核苷衍生物的组合物及其使用方法。 在一些实施方案中，本发明涉及制备烟酰基核糖苷的方法。 在一些实施方案中，本发明涉及含有烟酰基核苷的药物组合物和营养补充剂。 在进一步的实施方案中，本发明涉及使用促进细胞和组织中细胞内水平的烟酰胺腺嘌呤二核苷酸（NAD +）增加细胞和组织存活的烟酰胺核糖苷和烟酰胺核苷衍生物的方法。

公开(公告)号：US20120329748A1

公开(公告)日：2012-12-27

申请号：US13516190

申请日：2010-12-14

申请人： Anthony Sauve ,  Yana Cen

发明人： Anthony Sauve ,  Yana Cen

IPC分类号： A61K31/706 ,  C12Q1/34 ,  A61P3/00 ,  C12N9/96 ,  C12N5/071

CPC分类号： A61K31/706 ,  A61K31/341 ,  A61K31/443 ,  C07D405/04 ,  C07H19/048 ,  A61K2300/00

摘要： The invention provides a method of increasing a deacetylase activity of SIRT5 by contacting SIRT5 with an agent that binds SIRT5 and reduces the Km of SIRT5 for a substrate, thereby increasing the deacetylase activity of SIRT5. The invention also provides a method for treating a urea cycle disorder in a mammal, as well as a method of assaying a sirtuin modulator.

摘要翻译： 本发明提供了通过使SIRT5与结合SIRT5的试剂接触并降低基质的SIRT5的Km，从而增加SIRT5的脱乙酰酶活性而提高SIRT5的脱乙酰酶活性的方法。 本发明还提供了一种治疗哺乳动物尿素循环障碍的方法，以及测定沉默调节蛋白调节剂的方法。

公开(公告)号：US09322049B2

公开(公告)日：2016-04-26

申请号：US13516198

申请日：2010-12-14

申请人： Anthony Sauve ,  Ping Xu

发明人： Anthony Sauve ,  Ping Xu

IPC分类号： A61K31/70 ,  A61K31/185 ,  C12Q1/48

CPC分类号： C12Q1/48 ,  G01N2333/91142 ,  G01N2500/04

摘要： The invention provides a method of increasing a deacetylated activity of SIRT6 by contacting SIRT6 with an agent that binds SIRT6 and reduces the Km of SIRT6 for a substrate, thereby increasing the deacetylase activity of SIRT6. The invention also provides compounds of the formulas (II) and (III).

摘要翻译： 本发明提供了通过使SIRT6与结合SIRT6的试剂接触并降低底物的SIRT6的Km，从而增加SIRT6的脱乙酰酶活性而提高SIRT6脱乙酰化活性的方法。 本发明还提供式（II）和（III）的化合物。

公开(公告)号：US20060094670A1

公开(公告)日：2006-05-04

申请号：US11295120

申请日：2005-12-05

申请人： Anthony Sauve ,  Vern Schramm

发明人： Anthony Sauve ,  Vern Schramm

IPC分类号： A61K31/7056 ,  C07H19/048 ,  C07H19/056

CPC分类号： C07H19/052 ,  C07H19/048

摘要： The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds. Also provided are methods for inhibiting an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme, and methods for treating a disease or condition associated with an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme in a subject in need of treatment thereof.

公开(公告)号：US20090068695A1

公开(公告)日：2009-03-12

申请号：US12231880

申请日：2008-09-05

申请人： Vern L. Schramm ,  Jef D. Boeke ,  Anthony Sauve ,  Ivana Celic

发明人： Vern L. Schramm ,  Jef D. Boeke ,  Anthony Sauve ,  Ivana Celic

IPC分类号： C12Q1/34

CPC分类号： C12N9/1077 ,  C07H19/04 ,  C07H19/20 ,  C12N9/99 ,  C12P19/32

摘要： A novel compound, 2′/3′-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2′ and 3′ regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2′-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2′/3′-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2′/3′-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2′/3′-O-acetyl-ADP-ribose are also provided.

摘要翻译： 提供新的化合物2'/ 3'-O-乙酰基-ADP-核糖。 该化合物是O-乙酰基-ADP核糖的2'和3'区域异构体的混合物，并且由2'-O-乙酰基-ADP-核糖非酶催化形成，其是Sir2酶与 乙酰化肽和NAD +。 还提供了2'/ 3'-O-乙酰基-ADP-核糖的类似物。 另外，制备2'/ 3'-O-乙酰基-ADP-核糖的方法，确定测试化合物是否为Sir2酶抑制剂的方法，组合物中Sir2活性检测方法，乙酰化肽脱乙酰化的方法， 并提供了抑制乙酰化肽脱乙酰化的方法。 还提供了2'/ 3'-O-乙酰基-ADP-核糖的前药。

公开(公告)号：US20060089318A1

公开(公告)日：2006-04-27

申请号：US10516271

申请日：2003-05-30

申请人： Anthony Sauve ,  Vern Schramm

发明人： Anthony Sauve ,  Vern Schramm

IPC分类号： C07H19/048 ,  A61K31/7052

CPC分类号： C07H19/052 ,  C07H19/048

摘要： The present invention provides compounds having the formula: (I); Also provided are pro-drug compounds of the formula: (II); The invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds. Methods for inhibiting an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme using the above compounds, and methods for treating a disease or condition associated with an ADP-ribosyl transferase, ADP-‘ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme in a subject using the above compounds are also provided.

摘要翻译： 本发明提供具有下式的化合物：（I）; 还提供了下式的前药化合物：（II）; 本发明还提供含有上述化合物的药物组合物，使用上述化合物作为药物的方法，以及制备上述化合物的方法。 使用上述化合物抑制ADP-核糖基转移酶，ADP-核糖基环化酶，ADP-核糖基水解酶或NAD依赖性脱乙酰酶的方法，以及用于治疗与ADP-核糖基转移酶相关的疾病或病症的方法，ADP- 还提供了使用上述化合物的受试者中的环化酶，ADP-核糖基水解酶或NAD依赖性脱乙酰酶。

公开(公告)号：US20060058520A1

公开(公告)日：2006-03-16

申请号：US11248523

申请日：2005-10-12

申请人： Vern Schramm ,  Jef Boeke ,  Anthony Sauve ,  Ivana Celic

发明人： Vern Schramm ,  Jef Boeke ,  Anthony Sauve ,  Ivana Celic

IPC分类号： C07H19/20

CPC分类号： C12N9/1077 ,  C07H19/04 ,  C07H19/20 ,  C12N9/99 ,  C12P19/32

摘要： A novel compound, 2′/3′-O-acetyl-ADP-ribose, is provided. The compound is a mixture of the 2′ and 3′ regioisomers of O-acetyl-ADP ribose, and is formed nonenzymatically from 2′-O-acetyl-ADP-ribose, which is the newly discovered product of the reaction of Sir2 enzymes with acetylated peptides and NAD+. Analogs of 2′/3′-O-acetyl-ADP-ribose are also provided. Additionally, methods of preparing 2′/3′-O-acetyl-ADP-ribose, methods of determining whether a test compound is an inhibitor of a Sir2 enzyme, methods of detecting Sir2 activity in a composition, methods of deacetylating an acetylated peptide, and methods of inhibiting the deacetylation of an acetylated peptide are provided. Prodrugs of 2′/3′-O-acetyl-ADP-ribose are also provided.

摘要翻译： 提供新的化合物2'/ 3'-O-乙酰基-ADP-核糖。 该化合物是O-乙酰基-ADP核糖的2'和3'区域异构体的混合物，并且由2'-O-乙酰基-ADP-核糖非酶催化形成，其是Sir2酶与 乙酰化肽和NAD +。 还提供了2'/ 3'-O-乙酰基-ADP-核糖的类似物。 另外，制备2'/ 3'-O-乙酰基-ADP-核糖的方法，确定测试化合物是否为Sir2酶抑制剂的方法，组合物中Sir2活性检测方法，乙酰化肽脱乙酰化的方法， 并提供了抑制乙酰化肽脱乙酰化的方法。 还提供了2'/ 3'-O-乙酰基-ADP-核糖的前药。

公开(公告)号：US20130029930A1

公开(公告)日：2013-01-31

申请号：US13516198

申请日：2010-12-14

申请人： Anthony Sauve ,  Ping Xu

发明人： Anthony Sauve ,  Ping Xu

IPC分类号： C07C309/51 ,  C07C237/42 ,  A61K31/185 ,  C12N9/96 ,  A61K31/706

CPC分类号： C12Q1/48 ,  G01N2333/91142 ,  G01N2500/04

摘要： The invention provides a method of increasing a deacetylated activity of SIRT6 by contacting SIRT6 with an agent that binds SIRT6 and reduces the Km of SIRT6 for a substrate, thereby increasing the deacetylase activity of SIRT6. The invention also provides compounds of the formulas (II) and (III).

摘要翻译： 本发明提供了通过使SIRT6与结合SIRT6的试剂接触并降低底物的SIRT6的Km，从而增加SIRT6的脱乙酰酶活性而提高SIRT6脱乙酰化活性的方法。 本发明还提供式（II）和（III）的化合物。

公开(公告)号：US20090012148A1

公开(公告)日：2009-01-08

申请号：US11555152

申请日：2006-10-31

申请人： Frederick R. Maxfield ,  Anthony Sauve

发明人： Frederick R. Maxfield ,  Anthony Sauve

IPC分类号： A61K31/4025 ,  A61P9/10 ,  C12N5/08 ,  C12N5/06 ,  C07D405/02 ,  C07D403/02

CPC分类号： A61K31/53

摘要： Compounds disclosed herein may be used in disclosed methods for reducing the amount of cholesterol in a cell, for treating a patient suffering from a disorder characterized by cellular accumulation of cholesterol (such as Niemann-Pick Disease Type C or atherosclerosis), and/or for treating or preventing phospholipidosis. In some embodiments, the compounds may include a pyrrolone or triazine moiety.

摘要翻译： 本文公开的化合物可用于公开的用于减少细胞中胆固醇量的方法，用于治疗患有以胆固醇细胞积聚为特征的病症（例如，尼曼 - 皮克病C型或动脉粥样硬化）特征的患者，和/或 治疗或预防磷脂病。 在一些实施方案中，化合物可以包括吡咯酮或三嗪部分。

公开(公告)号：US09603862B2

公开(公告)日：2017-03-28

申请号：US13516190

申请日：2010-12-14

申请人： Anthony Sauve ,  Yana Cen

发明人： Anthony Sauve ,  Yana Cen

IPC分类号： A61K31/706 ,  A61K31/341 ,  A61K31/443 ,  C07D405/04 ,  C07H19/048

CPC分类号： A61K31/706 ,  A61K31/341 ,  A61K31/443 ,  C07D405/04 ,  C07H19/048 ,  A61K2300/00

摘要： The invention provides a method of increasing a deacetylase activity of SIRT5 by contacting SIRT5 with an agent that binds SIRT5 and reduces the Km of SIRT5 for a substrate, thereby increasing the deacetylase activity of SIRT5. The invention also provides a method for treating a urea cycle disorder in a mammal, as well as a method of assaying a sirtuin modulator.