公开(公告)号：WO2007064902A2

公开(公告)日：2007-06-07

申请号：PCT/US2006/046021

申请日：2006-12-01

Applicant: SIRTRIS PHARMACEUTICALS, INC. ,  SMITH, Jesse ,  MILNE, Jill ,  LYNCH, Amy ,  CARNEY, David ,  IFFLAND, Andre ,  BOSS, Olivier

Inventor： SMITH, Jesse ,  MILNE, Jill ,  LYNCH, Amy ,  CARNEY, David ,  IFFLAND, Andre ,  BOSS, Olivier

IPC: G01N33/68 ,  C12Q1/25

CPC classification number: G01N33/6851 ,  C12Q1/25 ,  G01N33/6842 ,  G01N2333/98

Abstract: Provided are methods for determining the activity of proteins that modulate the acetylation state of a protein substrate. The methods may be used for determining both acetyltransferase activity and deacetylase activity. The methods utilize mass spectrometry for determining the acetylation state of a substrate peptide. The methods may also be used to identify compounds that modulate the activity of a protein having acetyltransferase or deacetylase activity.

Abstract translation: 提供了用于测定调节蛋白质底物的乙酰化状态的蛋白质的活性的方法。 该方法可用于测定乙酰转移酶活性和脱乙酰酶活性。 该方法利用质谱法测定底物肽的乙酰化状态。 该方法还可用于鉴定调节具有乙酰转移酶或脱乙酰酶活性的蛋白质的活性的化合物。

公开(公告)号：WO2006094209A3

公开(公告)日：2007-01-11

申请号：PCT/US2006007655

申请日：2006-03-03

Applicant: SIRTRIS PHARMACEUTICALS INC ,  MILBURN MICHAEL ,  MILNE JILL ,  NORMINGTON KARL D

Inventor： MILBURN MICHAEL ,  MILNE JILL ,  NORMINGTON KARL D

IPC: C07D401/06 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/4427 ,  A61P9/00 ,  A61P25/28 ,  A61P35/00 ,  C07D209/10 ,  C07D209/30 ,  C07D401/14 ,  C07D403/06

CPC classification number: C07D401/06 ,  C07D235/24 ,  C07D235/28

Abstract: Provided herein are novel sirtuin-modulating compounds of formula ( Ia ) and methods of use thereof . The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了式（Ia）的新型沉默调节蛋白的调节性化合物及其使用方法。 沉默调节蛋白的调节化合物可用于增加细胞的寿命，以及治疗和/或预防各种各样的疾病和病症，包括例如与老化或紧张相关的疾病或病症，糖尿病，肥胖症，神经变性疾病， 心血管疾病，凝血障碍，炎症，癌症和/或潮红以及由线粒体活性增加所致的疾病或病症。 还提供了包含与另一种治疗剂组合的沉默调节蛋白的调节化合物的组合物。

公开(公告)号：WO2006094246A3

公开(公告)日：2006-12-14

申请号：PCT/US2006007773

申请日：2006-03-03

Applicant: SIRTRIS PHARMACEUTICALS INC ,  MILBURN MICHAEL ,  MILLNE JILL ,  NORMINGTON KARL D

Inventor： MILBURN MICHAEL ,  MILLNE JILL ,  NORMINGTON KARL D

IPC: A61P43/00 ,  A61K31/4402 ,  A61K31/4436 ,  A61K31/4995 ,  A61K31/5377 ,  A61P3/04 ,  A61P9/00 ,  A61P25/28

CPC classification number: C07D401/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14

Abstract: Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了新的沉默调节蛋白的调节化合物及其使用方法。 沉默调节蛋白的调节化合物可用于增加细胞的寿命，以及治疗和/或预防各种各样的疾病和病症，包括例如与老化或紧张相关的疾病或病症，糖尿病，肥胖症，神经变性疾病， 心血管疾病，凝血障碍，炎症，癌症和/或潮红以及由线粒体活性增加所致的疾病或病症。 还提供了包含与另一种治疗剂组合的沉默调节蛋白的调节化合物的组合物。

公开(公告)号：WO2006105440A2

公开(公告)日：2006-10-05

申请号：PCT/US2006012076

申请日：2006-03-30

Applicant: SIRTRIS PHARMACEUTICALS INC ,  MILBURN MICHAEL ,  MILNE JILL ,  NORMINGTON KARL D ,  NUNES JOSEPH J ,  SALZMANN THOMAS ,  SINCLAIR DAVID ,  WESTPHAL CHRISTOPH H

Inventor： MILBURN MICHAEL ,  MILNE JILL ,  NORMINGTON KARL D ,  NUNES JOSEPH J ,  SALZMANN THOMAS ,  SINCLAIR DAVID ,  WESTPHAL CHRISTOPH H

CPC classification number: C07H19/048 ,  A61K31/4436 ,  A61K31/445 ,  A61K31/706 ,  C07H7/06

Abstract: Provided herein are sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了沉默调节蛋白的调节性化合物及其使用方法。 沉默调节蛋白的调节化合物可用于增加细胞的寿命，以及治疗和/或预防各种各样的疾病和病症，包括例如与老化或紧张相关的疾病或病症，糖尿病，肥胖症，神经变性疾病， 心血管疾病，凝血障碍，炎症，癌症和/或潮红。 还提供了包含与另一种治疗剂组合的沉默调节蛋白的调节化合物的组合物。

公开(公告)号：WO2006094246A2

公开(公告)日：2006-09-08

申请号：PCT/US2006/007773

申请日：2006-03-03

Applicant: SIRTRIS PHARMACEUTICALS, INC. ,  MILBURN, Michael ,  MILLNE, Jill ,  NORMINGTON, Karl, D.

Inventor： MILBURN, Michael ,  MILLNE, Jill ,  NORMINGTON, Karl, D.

IPC: A61P43/00 ,  A61K31/4402 ,  A61K31/4436 ,  A61K31/4995

CPC classification number: C07D401/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14

Abstract: Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benfit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了新颖的瑟土因调节性化合物及其使用方法。 瑟土因调节性化合物可用于增加细胞寿命，以及治疗和/或预防各种疾病和病症，包括例如与衰老或压力相关的疾病或病症，糖尿病，肥胖症，神经退行性疾病， 心血管疾病，凝血障碍，炎症，癌症和/或潮红以及由线粒体活性增加引起的疾病或病症。 还提供了包含沉默调节蛋白调节化合物与另一种治疗剂组合的组合物。

公开(公告)号：WO2013059594A1

公开(公告)日：2013-04-25

申请号：PCT/US2012/061026

申请日：2012-10-19

Applicant: SIRTRIS PHARMACEUTICALS, INC. ,  BLUM, Charles, A. ,  DISCH, Jeremy, S. ,  SPRINGER, Stephanie, K.

Inventor： BLUM, Charles, A. ,  DISCH, Jeremy, S. ,  SPRINGER, Stephanie, K.

IPC: C07D487/04

CPC classification number: C07D487/04

Abstract: Provided herein are novel substituted bicyclic aza-heterocycle sirtuin- modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了新型取代的双环氮杂 - 杂环调节蛋白的调节化合物及其使用方法。 沉默调节蛋白的调节化合物可用于增加细胞的寿命，以及治疗和/或预防各种各样的疾病和病症，包括例如与老化或紧张相关的疾病或病症，糖尿病，肥胖症，神经变性疾病， 心血管疾病，血液凝固障碍，炎症，癌症和/或潮红以及将受益于增加的线粒体活性的疾病或病症。 还提供了包含与另一种治疗剂组合的沉默调节蛋白的调节化合物的组合物。

公开(公告)号：WO2011130595A2

公开(公告)日：2011-10-20

申请号：PCT/US2011/032628

申请日：2011-04-15

Applicant: SIRTRIS PHARMACEUTICALS, INC. ,  DAI, Han ,  RIERA, Thomas, V. ,  STEIN, Ross, L. ,  SZCZEPANKIEWICZ, Bruce

Inventor： DAI, Han ,  RIERA, Thomas, V. ,  STEIN, Ross, L. ,  SZCZEPANKIEWICZ, Bruce

IPC: C12Q1/37

CPC classification number: C07D513/04 ,  C07D401/04 ,  C07D401/14 ,  C07D417/14 ,  C07D519/00 ,  C12Q1/34 ,  C12Q1/37

Abstract: Provided are methods and compositions for detecting a compound that activates a sirtuin deacetylase activity on a fluorescent-free activation substrate in vitro. Further provided are sirtuin modulating compounds of the formulas (I) - (XXI), and related compounds (XXXI), (XXXII), (XXXIII), and (XXXIV), including the fluorescent free- substrate SIRT1 activator compounds of formulas (XL), (XI), (XII), and (XIII).

Abstract translation: 提供了用于在体外检测在无荧光活化底物上活化沉默调节蛋白脱乙酰酶活性的化合物的方法和组合物。 还提供了式（I） - （XXI）和相关化合物（XXXI），（XXXII），（XXXIII）和（XXXIV）的沉默调节蛋白调节性化合物，包括式（XL）的荧光自由基底物SIRT1活化剂 ），（XI），（XII）和（XIII）。

公开(公告)号：WO2010101949A1

公开(公告)日：2010-09-10

申请号：PCT/US2010/025963

申请日：2010-03-02

Applicant: SIRTRIS PHARMACEUTICALS, INC. ,  VU, Chi, B. ,  CASAUBON, Rebecca, L.

Inventor： VU, Chi, B. ,  CASAUBON, Rebecca, L.

IPC: C07D215/48 ,  A61K31/519 ,  C07D401/12 ,  A61K31/4375 ,  A61K31/5377 ,  C07D401/14 ,  A61K31/47 ,  A61K31/538 ,  C07D413/14 ,  A61K31/4709 ,  A61P3/00 ,  C07D417/12 ,  A61K31/497 ,  A61P5/50 ,  C07D417/14 ,  A61K31/501 ,  A61P9/00 ,  C07D487/04 ,  A61K31/506 ,  A61P35/02

CPC classification number: C07D471/04 ,  C07D215/48 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D413/14 ,  C07D417/04 ,  C07D417/12 ,  C07D417/14

Abstract: Provided herein are 8-substituted quinolines and related analogues as sirtuin-modulating compounds of Structural Formula (I) and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了8-取代的喹啉和相关的类似物作为结构式（I）的沉默调节蛋白的调节性化合物及其使用方法。 沉默调节蛋白的调节化合物可用于增加细胞的寿命，以及治疗和/或预防各种各样的疾病和病症，包括例如与老化或紧张相关的疾病或病症，糖尿病，肥胖症，神经变性疾病， 心血管疾病，血液凝固障碍，炎症，癌症和/或潮红以及将受益于增加的线粒体活性的疾病或病症。 还提供了包含与另一种治疗剂组合的沉默调节蛋白的调节化合物的组合物。

公开(公告)号：WO2010071853A1

公开(公告)日：2010-06-24

申请号：PCT/US2009/068865

申请日：2009-12-18

Applicant: SIRTRIS PHARMACEUTICALS, INC. ,  OALMANN, Christopher ,  DISCH, Jeremy, S. ,  NG, Pui, Yee ,  PERNI, Robert, B.

Inventor： OALMANN, Christopher ,  DISCH, Jeremy, S. ,  NG, Pui, Yee ,  PERNI, Robert, B.

IPC: C07D513/04 ,  A61P3/00 ,  A61P25/00 ,  A61K31/437 ,  A61P5/50 ,  A61P31/00 ,  A61K31/496 ,  A61P9/00 ,  A61P37/00 ,  A61K31/5377 ,  A61P19/00

CPC classification number: C07D513/04 ,  A61K31/437 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06

Abstract: Provided herein are novel sirtuin-modulating compounds of Structural Formula (Ia) and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了结构式（Ia）的新型沉默调节蛋白的调节性化合物及其使用方法。 沉默调节蛋白的调节化合物可用于增加细胞的寿命，以及治疗和/或预防各种各样的疾病和病症，包括例如与老化或紧张相关的疾病或病症，糖尿病，肥胖症，神经变性疾病， 心血管疾病，血液凝固障碍，炎症，癌症和/或潮红以及将受益于增加的线粒体活性的疾病或病症。 还提供了包含与另一种治疗剂组合的沉默调节蛋白的调节化合物的组合物。

公开(公告)号：WO2010037127A1

公开(公告)日：2010-04-01

申请号：PCT/US2009/058862

申请日：2009-09-29

Applicant: SIRTRIS PHARMACEUTICALS, INC. ,  OALMANN, Christopher ,  PERNI, Robert, B. ,  VU, Chi, B.

Inventor： OALMANN, Christopher ,  PERNI, Robert, B. ,  VU, Chi, B.

IPC: C07D311/22 ,  A61K31/353 ,  A61P3/10

CPC classification number: A61K31/5377 ,  A61K31/353 ,  A61K31/4025 ,  A61K31/4155 ,  A61K31/422 ,  A61K31/427 ,  A61K31/4433 ,  A61K31/4439 ,  A61K31/497 ,  A61K31/506 ,  A61K45/06 ,  C07D311/30 ,  C07D405/12 ,  C07D405/14 ,  C07D417/12 ,  C07D417/14 ,  A61K2300/00

Abstract: Provided herein are novel sirtuin-modulating compounds and methods of use thereof. The sirtuin-modulating compounds may be used for increasing the lifespan of a cell, and treating and/or preventing a wide variety of diseases and disorders including, for example, diseases or disorders related to aging or stress, diabetes, obesity, neurodegenerative diseases, cardiovascular disease, blood clotting disorders, inflammation, cancer, and/or flushing as well as diseases or disorders that would benefit from increased mitochondrial activity. Also provided are compositions comprising a sirtuin-modulating compound in combination with another therapeutic agent.

Abstract translation: 本文提供了新的沉默调节蛋白的调节化合物及其使用方法。 沉默调节蛋白的调节化合物可用于增加细胞的寿命，以及治疗和/或预防各种各样的疾病和病症，包括例如与老化或紧张相关的疾病或病症，糖尿病，肥胖症，神经变性疾病， 心血管疾病，血液凝固障碍，炎症，癌症和/或潮红以及将受益于增加的线粒体活性的疾病或病症。 还提供了包含与另一种治疗剂组合的沉默调节蛋白的调节化合物的组合物。