公开(公告)号：WO2012101065A3

公开(公告)日：2013-01-10

申请号：PCT/EP2012050909

申请日：2012-01-20

Applicant: NOVARTIS AG ,  ANTONIOS-MCCREA WILLIAM R ,  BARSANTI PAUL A ,  HU CHENG ,  JIN XIANMING ,  LIN XIAODONG ,  MARTIN ERIC J ,  PAN YUE ,  PFISTER KEITH B ,  RENHOWE PAUL A ,  SENDZIK MARTIN ,  SUTTON JAMES ,  WAN LIFENG

Inventor： ANTONIOS-MCCREA WILLIAM R ,  BARSANTI PAUL A ,  HU CHENG ,  JIN XIANMING ,  LIN XIAODONG ,  MARTIN ERIC J ,  PAN YUE ,  PFISTER KEITH B ,  RENHOWE PAUL A ,  SENDZIK MARTIN ,  SUTTON JAMES ,  WAN LIFENG

IPC: C07D401/04 ,  A61K31/444 ,  A61K31/506 ,  A61P35/00 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

CPC classification number: C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

Abstract: The present invention provides a pyrimidine compound of formula (I): wherein one of X and Y but not both is N, and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, deuterated versions, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.

Abstract translation: 本发明提供式（I）的嘧啶化合物：其中X和Y之一，但不是二者均为N，以及其药学上可接受的盐，对映异构体，立体异构体，旋转异构体，互变异构体，非对映异构体，氘化形式或其外消旋体。 这些化合物抑制CDK9的活性，因此可用作药物。 还提供了使用式I化合物及其异构体治疗由CDK9介导的疾病或病症的方法，以及包含这些化合物的药物组合物。

公开(公告)号：WO2007021794A1

公开(公告)日：2007-02-22

申请号：PCT/US2006/031129

申请日：2006-08-09

Applicant: NOVARTIS AG ,  BARSANTI, Paul A. ,  XIA, Yi ,  WANG, Weibo ,  MENDENHALL, Kris G. ,  LAGNITON, Liana M. ,  RAMURTHY, Savithri ,  PHILLIPS, Megan C. ,  SUBRAMANIAN, Sharadha ,  BOYCE, Rustum ,  BRAMMEIER, Nathan M. ,  CONSTANTINE, Ryan ,  DUHL, David ,  WALTER, Annette O. ,  ABRAMS, Tinya J. ,  RENHOWE, Paul A.

Inventor： BARSANTI, Paul A. ,  XIA, Yi ,  WANG, Weibo ,  MENDENHALL, Kris G. ,  LAGNITON, Liana M. ,  RAMURTHY, Savithri ,  PHILLIPS, Megan C. ,  SUBRAMANIAN, Sharadha ,  BOYCE, Rustum ,  BRAMMEIER, Nathan M. ,  CONSTANTINE, Ryan ,  DUHL, David ,  WALTER, Annette O. ,  ABRAMS, Tinya J. ,  RENHOWE, Paul A.

IPC: C07D401/14 ,  C07D233/54 ,  C07D403/12 ,  C07D403/06 ,  C07D409/12 ,  C07D413/12 ,  C07D407/12 ,  A61K31/4178 ,  A61K31/4545 ,  A61P35/00

CPC classification number: C07D401/14 ,  C07D233/64 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D413/12

Abstract: The present invention relates to new substituted imidazole compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the derivatives together with pharmaceutically acceptable carriers, and uses of the compounds. The compounds of the invention have the following general formula (I).

Abstract translation: 本发明涉及新的取代的咪唑化合物及其药学上可接受的盐，酯或前药，衍生物的组合物和药学上可接受的载体，以及该化合物的用途。 本发明的化合物具有以下通式（I）。

公开(公告)号：WO2004018419A2

公开(公告)日：2004-03-04

申请号：PCT/US2003/025990

申请日：2003-08-19

Applicant: CHIRON CORPORATION ,  BARSANTI, Paul, A. ,  BUSSIERE, Dirksen ,  HARRISON, Stephen, D. ,  HEISE, Carla, C. ,  JANSEN, Johanna, M. ,  JAZAN, Elisa ,  MACHAJEWSKI, Timothy, D. ,  McBRIDE, Christopher ,  McCREA, William, R. ,  NG, Simon ,  NI, Zhi-Jie ,  PECCHI, Sabina ,  PFISTER, Keith ,  RAMURTHY, Savithri ,  RENHOWE, Paul, A. ,  SHAFER, Cynthia, M. ,  SILVER, Joel, B. ,  WAGMAN, Allan ,  WEISMANN, Marion

Inventor： BARSANTI, Paul, A. ,  BUSSIERE, Dirksen ,  HARRISON, Stephen, D. ,  HEISE, Carla, C. ,  JANSEN, Johanna, M. ,  JAZAN, Elisa ,  MACHAJEWSKI, Timothy, D. ,  McBRIDE, Christopher ,  McCREA, William, R. ,  NG, Simon ,  NI, Zhi-Jie ,  PECCHI, Sabina ,  PFISTER, Keith ,  RAMURTHY, Savithri ,  RENHOWE, Paul, A. ,  SHAFER, Cynthia, M. ,  SILVER, Joel, B. ,  WAGMAN, Allan ,  WEISMANN, Marion

IPC: C07D

CPC classification number: C07D401/04 ,  A61K31/4375 ,  A61K31/4709 ,  A61K31/496 ,  A61K31/52 ,  C07D401/14 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D453/02 ,  C07D453/06 ,  C07D471/04

Abstract: Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

Abstract translation: 提供了抑制各种酶和治疗各种病症的方法，其包括向受试者施用结构I或1B的化合物，其药学上可接受的盐，其互变异构体或其药学上可接受的盐 互变异构体。 具有结构I和IB的化合物具有以下结构并且具有本文所述的变量。 此类化合物可用于制备用于抑制各种酶的药物和用于治疗由这些酶介导的病症的药物。

公开(公告)号：WO2014151030A1

公开(公告)日：2014-09-25

申请号：PCT/US2014/024795

申请日：2014-03-12

Applicant: NOVARTIS AG ,  IRM LLC ,  BARSANTI, Paul A. ,  CHAMOIN, Sylvie ,  DOUMAMPOUOM-METOUL, Lionel ,  GEIERSTANGER, Bernhard Hubert ,  GROTZFELD, Robert Martin ,  GUERRO-LAGASSE, Stephanie ,  JONES, Darryl Brynley ,  KARPOV, Alexei ,  LAFRANCE, Marc ,  NIETO-OBERHUBER, Cristina ,  OU, Weijia ,  PIIZZI, Grazia

Inventor： BARSANTI, Paul A. ,  CHAMOIN, Sylvie ,  DOUMAMPOUOM-METOUL, Lionel ,  GEIERSTANGER, Bernhard Hubert ,  GROTZFELD, Robert Martin ,  GUERRO-LAGASSE, Stephanie ,  JONES, Darryl Brynley ,  KARPOV, Alexei ,  LAFRANCE, Marc ,  NIETO-OBERHUBER, Cristina ,  OU, Weijia ,  PIIZZI, Grazia

IPC: A61K47/48 ,  A61P35/00 ,  C07D405/14 ,  C07D233/64 ,  C07D401/12 ,  C07D249/10

CPC classification number: C07D249/10 ,  A61K47/6803 ,  C07D233/64 ,  C07D239/91 ,  C07D249/08 ,  C07D311/22 ,  C07D401/12 ,  C07D403/06 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14

Abstract: Disclosed herein are immunoconjugates comprising an inhibitor of Eg5 linked to an antigen binding moiety such as an antibody, useful for treating cell proliferative disorders. Also disclosed are novel inhibitors of Eg5 that can be used either alone or as part of an immunoconjugate to treat cell proliferation disorders. The Eg5 inhibitors include compounds of this formula as described herein: [insert last structure from page 68 here] The invention further provides pharmaceutical compositions comprising these compounds and immunoconjugates, optionally including a therapeutic co-agent, and methods to use these compounds, conjugates and compositions for treating cell proliferation disorders.

Abstract translation: 本文公开了包含与抗原结合部分如抗体连接的Eg5抑制剂的免疫缀合物，其可用于治疗细胞增殖性疾病。 还公开了Eg5的新型抑制剂，其可以单独使用或作为免疫缀合物的一部分用于治疗细胞增殖障碍。 Eg5抑制剂包括本文所述的该式的化合物：[在此从第68页开始插入最后的结构]本发明还提供包含这些化合物和免疫偶联物的药物组合物，任选地包括治疗性助剂，以及使用这些化合物，缀合物和 用于治疗细胞增殖障碍的组合物。

公开(公告)号：WO2012101065A2

公开(公告)日：2012-08-02

申请号：PCT/EP2012/050909

申请日：2012-01-20

Applicant: NOVARTIS AG ,  ANTONIOS-MCCREA, William R. ,  BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  LIN, Xiaodong ,  MARTIN, Eric J. ,  PAN, Yue ,  PFISTER, Keith B ,  RENHOWE, Paul A. ,  SENDZIK, Martin ,  SUTTON, James ,  WAN, Lifeng

Inventor： ANTONIOS-MCCREA, William R. ,  BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  LIN, Xiaodong ,  MARTIN, Eric J. ,  PAN, Yue ,  PFISTER, Keith B ,  RENHOWE, Paul A. ,  SENDZIK, Martin ,  SUTTON, James ,  WAN, Lifeng

IPC: C07D401/04

CPC classification number: C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14

Abstract: The present invention provides a pyrimidine compound of formula (I): wherein one of X and Y but not both is N, and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, deuterated versions, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.

Abstract translation: 本发明提供式（I）的嘧啶化合物：其中X和Y之一而不是二者均为N，以及其药学上可接受的盐，对映异构体，立体异构体，旋转异构体，互变异构体，非对映异构体，氘化形式或其外消旋体。 这些化合物抑制CDK9的活性，因此可用作药物。 还提供了使用式I化合物及其异构体治疗由CDK9介导的疾病或病症的方法，以及包含这些化合物的药物组合物。

公开(公告)号：WO2012101064A1

公开(公告)日：2012-08-02

申请号：PCT/EP2012/050907

申请日：2012-01-20

Applicant: NOVARTIS AG ,  BARSANTI, Paul, A. ,  HU, Cheng ,  JIN, Xianming ,  NG, Simon, C. ,  PFISTER, Keith, B. ,  SENDZIK, Martin ,  SUTTON, James

Inventor： BARSANTI, Paul, A. ,  HU, Cheng ,  JIN, Xianming ,  NG, Simon, C. ,  PFISTER, Keith, B. ,  SENDZIK, Martin ,  SUTTON, James

IPC: C07D405/14 ,  A61K31/506 ,  A61P9/00 ,  A61P29/00 ,  A61P35/00

CPC classification number: C07D405/14 ,  C07D213/73 ,  C07D213/75 ,  C07D401/14 ,  C07D405/12 ,  C07D413/14

Abstract: The present invention provides a compound of the general formula (1): wherein one of X and Y is N and the other is an optionally substituted carbon atom, and Z 2 -Z 5 represent one or two nitrogen atoms, as further described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals and as components of pharmaceutical compositions. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds described herein or pharmaceutical compositions comprising such compounds.

Abstract translation: 本发明提供通式（1）的化合物：其中X和Y中的一个是N，另一个是任选取代的碳原子，Z 2 -Z 5代表一个或两个氮原子，如本文进一步描述的，包括药学上 可接受的盐，对映异构体，立体异构体，旋转异构体，互变异构体，非对映体或其外消旋体。 这些化合物抑制CDK9的活性，因此可用作药物和药物组合物的组分。 还提供了使用本文所述的化合物或包含这些化合物的药物组合物治疗由CDK9介导的疾病或病症的方法。

公开(公告)号：WO2012101062A1

公开(公告)日：2012-08-02

申请号：PCT/EP2012/050903

申请日：2012-01-20

Applicant: NOVARTIS AG ,  ANTONIOS-MCCREA, William R. ,  BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  MARTIN, Eric J. ,  PAN, Yue ,  LIN, Xiaodong ,  PFISTER, Keith B. ,  RENHOWE, Paul A. ,  SENDZIK, Martin ,  SUTTON, James ,  WAN, Lifeng

Inventor： ANTONIOS-MCCREA, William R. ,  BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  MARTIN, Eric J. ,  PAN, Yue ,  LIN, Xiaodong ,  PFISTER, Keith B. ,  RENHOWE, Paul A. ,  SENDZIK, Martin ,  SUTTON, James ,  WAN, Lifeng

IPC: C07D213/74 ,  C07D401/04 ,  C07D405/14 ,  C07D413/14 ,  C07D491/107 ,  A61K31/444 ,  A61K31/505 ,  A61K31/553 ,  A61P35/00 ,  A61P29/00 ,  A61P9/00 ,  A61P37/00 ,  A61P31/18

CPC classification number: C07D401/14 ,  C07D213/74 ,  C07D401/04 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D487/04 ,  C07D491/107

Abstract: The present invention provides a compound of formula (II) where R 1 is a substituted alkyl, heterocyclic, or cycloalkyl, group, and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof, and pharmaceutical compositions comprising these compounds. Also provided are methods of using these compounds to treat a disease or condition mediated by CDK9, such as cancers and other conditions described herein.

Abstract translation: 本发明提供式（II）化合物，其中R 1是取代的烷基，杂环或环烷基，基团及其药学上可接受的盐，对映异构体，立体异构体，旋转异构体，互变异构体，非对映体或外消旋体，以及包含这些化合物 。 还提供了使用这些化合物治疗由CDK9介导的疾病或病症的方法，例如本文所述的癌症和其它病症。

公开(公告)号：WO2012101066A1

公开(公告)日：2012-08-02

申请号：PCT/EP2012/050914

申请日：2012-01-20

Applicant: NOVARTIS AG ,  ANTONIOS-MCCREA, William R. ,  BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  LIN, Xiaodong ,  MARTIN, Eric J. ,  PAN, Yue ,  PFISTER, Keith B. ,  RENHOWE, Paul A. ,  SENDZIK, Martin ,  SUTTON, James ,  WAN, Lifeng

Inventor： ANTONIOS-MCCREA, William R. ,  BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  LIN, Xiaodong ,  MARTIN, Eric J. ,  PAN, Yue ,  PFISTER, Keith B. ,  RENHOWE, Paul A. ,  SENDZIK, Martin ,  SUTTON, James ,  WAN, Lifeng

IPC: C07D213/74 ,  C07D401/04 ,  C07D405/14 ,  A61K31/444 ,  A61P35/00

CPC classification number: C07D213/74 ,  C07D401/04 ,  C07D405/14

Abstract: The present invention provides a compound of formula (I): and pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.

Abstract translation: 本发明提供式（I）化合物及其药学上可接受的盐，对映体，立体异构体，旋转异构体，互变异构体，非对映体或其外消旋物。 这些化合物抑制CDK9的活性，因此可用作药物。 还提供了使用式I化合物及其异构体治疗由CDK9介导的疾病或病症的方法，以及包含这些化合物的药物组合物。

公开(公告)号：WO2012101063A1

公开(公告)日：2012-08-02

申请号：PCT/EP2012/050906

申请日：2012-01-20

Applicant: NOVARTIS AG ,  BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  NG, Simon C. ,  PFISTER, Keith B. ,  SENDZIK, Martin ,  SUTTON, James

Inventor： BARSANTI, Paul A. ,  HU, Cheng ,  JIN, Xianming ,  NG, Simon C. ,  PFISTER, Keith B. ,  SENDZIK, Martin ,  SUTTON, James

IPC: C07D405/14 ,  A61K31/444 ,  A61P35/00 ,  C07D413/14 ,  C07D213/75

CPC classification number: C07D213/75 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14

Abstract: The present invention provides a compound of general formula:wherein Z 2 -Z 6 include one or two nitrogen atoms as described herein, including pharmaceutically acceptable salts, enantiomers, stereoisomers, rotamers, tautomers, diastereomers, or racemates thereof. These compounds inhibit the activity of CDK9 and are thus useful as pharmaceuticals. Also provided are methods of treating a disease or condition mediated by CDK9 using the compounds of Formula I and isomers thereof, and pharmaceutical compositions comprising such compounds.

Abstract translation: 本发明提供通式如下的化合物：其中Z2-Z6包括如本文所述的一个或两个氮原子，包括其药学上可接受的盐，对映异构体，立体异构体，旋转异构体，互变异构体，非对映体或其外消旋体。 这些化合物抑制CDK9的活性，因此可用作药物。 还提供了使用式I化合物及其异构体治疗由CDK9介导的疾病或病症的方法，以及包含这些化合物的药物组合物。

公开(公告)号：WO2011128381A1

公开(公告)日：2011-10-20

申请号：PCT/EP2011/055840

申请日：2011-04-13

Applicant: NOVARTIS AG ,  ABRAMS, Tinya ,  BARSANTI, Paul, A. ,  DING, Yu ,  DUHL, David ,  HAN, Wooseok ,  HU, Cheng ,  PAN, Yue

Inventor： ABRAMS, Tinya ,  BARSANTI, Paul, A. ,  DING, Yu ,  DUHL, David ,  HAN, Wooseok ,  HU, Cheng ,  PAN, Yue

IPC: C07D249/08 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  A61P35/00 ,  A61K31/55

CPC classification number: C07D403/12 ,  A61K31/4196 ,  A61K31/5377 ,  A61K45/06 ,  C07D207/10 ,  C07D249/08 ,  C07D405/12 ,  C07D405/14 ,  C07D413/14

Abstract: The present invention provides triazole compounds of Formula (I) : as further described herein. The invention also provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I), and a method of treating a disorder mediated, at least in part, by KSP in a mammalian patient comprising administering to a mammalian patient in need of such treatment a therapeutically effective amount of a compound of Formula (I).

Abstract translation: 本发明提供式（I）的三唑化合物：如本文进一步描述的。 本发明还提供了包含治疗有效量的式（I）化合物的药物组合物，以及治疗哺乳动物患者至少部分地由KSP介导的病症的方法，包括向需要的哺乳动物患者施用 治疗有效量的式（I）化合物。