公开(公告)号：WO2010151601A1

公开(公告)日：2010-12-29

申请号：PCT/US2010/039685

申请日：2010-06-23

申请人： GENENTECH, INC. ,  BERGERON, Philippe ,  COHEN, Frederick ,  ESTRADA, Anthony ,  KOEHLER, Michael F.T. ,  LEE, Wendy ,  LY, Cuong ,  LYSSIKATOS, Joseph P. ,  PEI, Zhonghua ,  ZHAO, Xianrui

发明人： BERGERON, Philippe ,  COHEN, Frederick ,  ESTRADA, Anthony ,  KOEHLER, Michael F.T. ,  LEE, Wendy ,  LY, Cuong ,  LYSSIKATOS, Joseph P. ,  PEI, Zhonghua ,  ZHAO, Xianrui

IPC分类号： A01N43/54

CPC分类号： C07D491/052 ,  C07D491/048 ,  C07D491/18 ,  C07D519/00

摘要： Disclosed are compounds of Formula (I), including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR). Formula (I).

摘要翻译： 公开了式（I）化合物，其包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物和药学上可接受的盐，其可用于调节PIKK相关激酶信号传导，例如mTOR和用于治疗疾病（例如癌症 ），其至少部分地由PIKK信号传导途径的失调（例如，mTOR）介导。 式（I）。

公开(公告)号：WO2010077663A2

公开(公告)日：2010-07-08

申请号：PCT/US2009/067157

申请日：2009-12-08

申请人： INOTEK PHARMACEUTICALS CORPORATION ,  JAGTAP, Prakash ,  PHAM-HUU, Duy-Phong ,  COHEN, Frederick ,  HU, Huiyong ,  WANG, Xiaojing

发明人： JAGTAP, Prakash ,  PHAM-HUU, Duy-Phong ,  COHEN, Frederick ,  HU, Huiyong ,  WANG, Xiaojing

IPC分类号： C07D513/04 ,  C07D487/04 ,  C07D403/08 ,  A61P35/00 ,  A61K31/4738

CPC分类号： C07D221/18 ,  A61K31/4738 ,  C07D401/04 ,  C07D401/06 ,  C07D403/06 ,  C07D413/04 ,  C07D471/04 ,  C07D495/04

摘要： Provided herein are tetracyclic 1 H -indeno[1,2- b ]pyridine-2(5 H )-one analogs and derivatives, compositions comprising an effective amount of a tetracyclic 1 H - indeno[1,2- b ]pyridine-2(5 H )-one analog and/or derivative and methods for treating or preventing an inflammatory disease, a reperfusion injury, diabetes mellitus, a diabetic complication, a reoxygenation injury resulting from organ transplantation, an ischemic condition, a neurodegenerative disease, renal failure, a vascular disease, a cardiovascular disease, an ocular or ophthalmologic disease, cancer, a complication of prematurity, cardiomyopathy, retinopathy, nephropathy, contrast induced nephropathy, neuropathy, erectile dysfunction or urinary incontinence, comprising administering to a subject in need thereof an effective amount of a tetracyclic 1 H - indeno[1,2- b ]pyridine-2(5 H )-one analog or derivative.

摘要翻译： 本文提供的是四环的1H-茚并[1,2-b]吡啶-2（5H） - 酮类似物和衍生物，包含有效量的四环的1H-茚并[1,2-b]吡啶-2（5H） - 用于治疗或预防炎性疾病，再灌注损伤，糖尿病，糖尿病并发症，器官移植引起的再氧化损伤，缺血性疾病，神经变性疾病，肾衰竭，血管疾病的类似物和/或衍生物和方法 心血管疾病，眼睛或眼科疾病，癌症，早产儿并发症，心肌病，视网膜病变，肾病，造影剂肾病，神经病，勃起功能障碍或尿失禁，包括向有需要的受试者施用有效量的四环 1H-茚并[1,2-b]吡啶-2（5H） - 酮类似物或衍生物。

公开(公告)号：WO2007103308A2

公开(公告)日：2007-09-13

申请号：PCT/US2007005583

申请日：2007-03-06

申请人： ARRAY BIOPHARMA INC ,  GENENTECH INC ,  BLAKE JAMES F ,  BOYD STEVEN ARMEN ,  COHEN FREDERICK ,  DE MEESE JASON ,  FONG KIN CHIU ,  GAUDINO JOHN J ,  KAPLAN TOMAS ,  MARLOW ALLISON L ,  SEO JEONGBEOB ,  THOMAS ALLEN A ,  TIAN HONGQI ,  YOUNG WENDY B

发明人： BLAKE JAMES F ,  BOYD STEVEN ARMEN ,  COHEN FREDERICK ,  DE MEESE JASON ,  FONG KIN CHIU ,  GAUDINO JOHN J ,  KAPLAN TOMAS ,  MARLOW ALLISON L ,  SEO JEONGBEOB ,  THOMAS ALLEN A ,  TIAN HONGQI ,  YOUNG WENDY B

CPC分类号： C07D471/04

摘要： Compounds of Formulas (Ia) and (Ib), and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

摘要翻译： 式（Ia）和（Ib）的化合物及其立体异构体，几何异构体，互变异构体，溶剂合物，代谢物和药学上可接受的盐可用于抑制受体酪氨酸激酶和用于治疗由此介导的病症。 使用式Ia和Ib化合物及其立体异构体，几何异构体，互变异构体，溶剂化物及其药学上可接受的盐的方法用于体外，原位和体内诊断，预防或治疗哺乳动物细胞中的这种病症或相关病理学 条件被公开。

公开(公告)号：WO2005094818A1

公开(公告)日：2005-10-13

申请号：PCT/US2005/009328

申请日：2005-03-22

申请人： GENENTECH, INC. ,  COHEN, Frederick ,  FAIRBROTHER, Wayne ,  FLYGARE, John ,  TSUI, Vickie, Hsiao-Wei ,  KETELTAS, Stephen, Franz

发明人： COHEN, Frederick ,  FAIRBROTHER, Wayne ,  FLYGARE, John ,  TSUI, Vickie, Hsiao-Wei ,  KETELTAS, Stephen, Franz

IPC分类号： A61K31/403

CPC分类号： C07K5/06026 ,  C07K14/4747

摘要： The invention provides novel inhibitors of IAP that are useful as a therapeutic agents for treating malignancies where the compounds have the general formula (I) in which X 1 and X 2 are independently O or S; L is a bond or -C(X 3 )-, -C(X 3 )NR 12 , -C(X 3 )O- wherein X 3 is O or S and R 12 is H or R 1 ; R 1 is alkyl, a carbocycle, carbocycle-substituted alkyl, a heterocycle or heterocycle-substituted alkyl, wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, haloalkyl, alkoxy, alkylsulfonyl, amino, nitro, aryl and heteroaryl; R 2 is alkyl, cycloalkyl, cycloalkylalkyl, aryl, aralkyl, a heterocycle or heterocyclylalkyl; R 3 is H or alkyl; R 4 and R 4' are independently H, alkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl, or heteroaralkyl wherein each is optionally substituted with halogen, hydroxyl, mercapto, carboxyl, alkyl, alkoxy, amino and nitro; R 5 , and R 5' are each independently H or alkyl; R 6 is H or alkyl; and salts and solvates thereof.

摘要翻译： 本发明提供了可用作治疗恶性肿瘤的治疗剂的新的IAP抑制剂，其中化合物具有其中X 1和X 2独立地为O或S的通式（I）; L是键或-C（X3） - ， - C（X3）NR12，-C（X3）O-，其中X3是O或S，R12是H或R1; R 1是烷基，碳环，碳环取代的烷基，杂环或杂环取代的烷基，其中各自任选被卤素，羟基，巯基，羧基，烷基，卤代烷基，烷氧基，烷基磺酰基，氨基，硝基，芳基和杂芳基取代; R2是烷基，环烷基，环烷基烷基，芳基，芳烷基，杂环或杂环基烷基; R3是H或烷基; R 4和R 4'独立地是H，烷基，芳基，芳烷基，环烷基，环烷基烷基，杂芳基或杂芳烷基，其中各自任选被卤素，羟基，巯基，羧基，烷基，烷氧基，氨基和硝基取代; R5和R5'各自独立地为H或烷基; R6是H或烷基; 及其盐和溶剂合物。

公开(公告)号：WO2010014939A1

公开(公告)日：2010-02-04

申请号：PCT/US2009/052469

申请日：2009-07-31

申请人： GENENTECH, INC. ,  BERGERON, Philippe ,  COHEN, Frederick ,  ESTRADA, Anthony ,  KOEHLER, Michael, F. T. ,  LAU, Kevin, Hon Luen ,  LY, Cuong ,  LYSSIKATOS, Joseph, P. ,  ORTWINE, Daniel, Fred ,  PEI, Zhonghua ,  ZHAO, Xianrui

发明人： BERGERON, Philippe ,  COHEN, Frederick ,  ESTRADA, Anthony ,  KOEHLER, Michael, F. T. ,  LAU, Kevin, Hon Luen ,  LY, Cuong ,  LYSSIKATOS, Joseph, P. ,  ORTWINE, Daniel, Fred ,  PEI, Zhonghua ,  ZHAO, Xianrui

IPC分类号： C07D239/02

CPC分类号： C07D471/18 ,  C07D471/14

摘要： Disclosed are compounds of Formula I, including steroisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, that are useful in modulating PIKK related kinase signaling, e.g., mTOR, and for the treatment of diseases (e.g., cancer) that are mediated at least in part by the dysregulation of the PIKK signaling pathway (e.g., mTOR).

摘要翻译： 公开了式I化合物，包括立体异构体，几何异构体，互变异构体，溶剂合物，代谢物和药学上可接受的盐，其可用于调节PIKK相关激酶信号传导，例如mTOR，以及用于治疗疾病（例如癌症）， 至少部分地由PIKK信号通路的失调（例如mTOR）介导。

公开(公告)号：WO2007103308A3

公开(公告)日：2007-09-13

申请号：PCT/US2007/005583

申请日：2007-03-06

申请人： ARRAY BIOPHARMA INC. ,  GENENTECH, INC. ,  BLAKE, James F. ,  BOYD, Steven Armen ,  COHEN, Frederick ,  DE MEESE, Jason ,  FONG, Kin Chiu ,  GAUDINO, John J. ,  KAPLAN, Tomas ,  MARLOW, Allison L. ,  SEO, Jeongbeob ,  THOMAS, Allen A. ,  TIAN, Hongqi ,  YOUNG, Wendy B.

发明人： BLAKE, James F. ,  BOYD, Steven Armen ,  COHEN, Frederick ,  DE MEESE, Jason ,  FONG, Kin Chiu ,  GAUDINO, John J. ,  KAPLAN, Tomas ,  MARLOW, Allison L. ,  SEO, Jeongbeob ,  THOMAS, Allen A. ,  TIAN, Hongqi ,  YOUNG, Wendy B.

IPC分类号： C07D471/04 ,  A61K31/437 ,  A61P35/00

摘要： Compounds of Formulas (Ia) and (Ib), and stereoisomers, geometric isomers, tautomers, solvates, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting receptor tyrosine kinases and for treating disorders mediated thereby. Methods of using compounds of Formula Ia and Ib, and stereoisomers, geometric isomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

公开(公告)号：WO2006125227A2

公开(公告)日：2006-11-23

申请号：PCT/US2006019876

申请日：2006-05-18

申请人： GENENTECH INC ,  COHEN FREDERICK ,  FAIRBROTHER WAYNE J ,  QUAN CLIFFORD ,  SUTHERLIN DANIEL P ,  WOLF BENI B

发明人： COHEN FREDERICK ,  FAIRBROTHER WAYNE J ,  QUAN CLIFFORD ,  SUTHERLIN DANIEL P ,  WOLF BENI B

CPC分类号： C07F5/025

摘要： Amino terminus-blocked peptide boronate compounds of Formulas (I) and (II) are useful for inhibiting Fibroblast Activation Protein (FAP) and other proteases, and for treating disorders mediated by FAP. Methods of using the amino terminus blocked peptide boronate compounds, and stereoisomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

摘要翻译： 式（I）和（II）的氨基末端封闭的肽硼酸酯化合物可用于抑制成纤维细胞激活蛋白（FAP）和其它蛋白酶，以及用于治疗由FAP介导的病症。 使用氨基末端阻断肽硼酸酯化合物及其立体异构体，互变异构体，溶剂合物及其药学上可接受的盐的方法用于体外，原位和体内诊断，预防或治疗哺乳动物细胞或相关病理学病症中的这种病症。 披露。

公开(公告)号：WO2018023081A1

公开(公告)日：2018-02-01

申请号：PCT/US2017/044534

申请日：2017-07-28

申请人： ACHAOGEN, INC. ,  COHEN, Frederick ,  KANE, Timothy Robert ,  DOZZO, Paola ,  HILDEBRANDT, Darin James ,  LINSELL, Martin Sheringham ,  MACHAJEWSKI, Timothy D. ,  MCENROE, Glenn A.

发明人： COHEN, Frederick ,  KANE, Timothy Robert ,  DOZZO, Paola ,  HILDEBRANDT, Darin James ,  LINSELL, Martin Sheringham ,  MACHAJEWSKI, Timothy D. ,  MCENROE, Glenn A.

IPC分类号： C07D471/04 ,  A61K31/519 ,  A61P31/04

摘要： The disclosure relates to antibacterial compounds having the Formula (I), where R1, R2, R3, R4, R8, n, and p are described herein, as well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof, pharmaceutical compositions comprising such compounds, methods of treating bacterial infections by the administration of such compounds, and processes for the preparation of the compounds.

摘要翻译： 本公开涉及具有式（I）的抗菌化合物，其中R 1，R 2，R 3，R 4，R 8，n和p在本文中描述，以及其立体异构体，药学上可接受的盐，酯 及其前药，包含此类化合物的药物组合物，通过施用此类化合物来治疗细菌感染的方法，以及制备所述化合物的方法。

公开(公告)号：WO2006125227A3

公开(公告)日：2006-11-23

申请号：PCT/US2006/019876

申请日：2006-05-18

申请人： GENENTECH, INC. ,  COHEN, Frederick ,  FAIRBROTHER, Wayne J. ,  QUAN, Clifford ,  SUTHERLIN, Daniel P. ,  WOLF, Beni B.

发明人： COHEN, Frederick ,  FAIRBROTHER, Wayne J. ,  QUAN, Clifford ,  SUTHERLIN, Daniel P. ,  WOLF, Beni B.

IPC分类号： C07F5/02 ,  A61K31/00 ,  A61P35/00

摘要： Amino terminus-blocked peptide boronate compounds of Formulas (I) and (II) are useful for inhibiting Fibroblast Activation Protein (FAP) and other proteases, and for treating disorders mediated by FAP. Methods of using the amino terminus blocked peptide boronate compounds, and stereoisomers, tautomers, solvates and pharmaceutically acceptable salts thereof, for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions are disclosed.

公开(公告)号：WO2006069063A1

公开(公告)日：2006-06-29

申请号：PCT/US2005/046161

申请日：2005-12-19

申请人： GENENTECH, INC. ,  COHEN, Frederick ,  TSUI, Vickie Hsiao-wei ,  LY, Cuong ,  FLYGARE, John, A.

发明人： COHEN, Frederick ,  TSUI, Vickie Hsiao-wei ,  LY, Cuong ,  FLYGARE, John, A.

IPC分类号： C07D417/04 ,  C07D417/14 ,  A61K31/427 ,  A61P35/00

CPC分类号： C07D471/04 ,  C07D417/04 ,  C07D417/14

摘要： The invention provides novel inhibitors of IAP that are useful as therapeutic agents for treating malignancies where the compounds have the general formula (I), wherein A,Q,X 1 ,X 2 ,Y,R 1 ,R 2 ,R 3 ,R 4 ,R 4’ ,R 5 ,R 6 and R 6’ are described herein.

摘要翻译： 本发明提供了新的IAP抑制剂，其可用作治疗恶性肿瘤的治疗剂，其中化合物具有通式（I），其中A，Q，X 1，X 2， >，Y，R _{1 ，R 2 ，R 3 ，R 4 ，R 4' 本文描述了R 5，R 6和R 6'。}