公开(公告)号：EP1836296A1

公开(公告)日：2007-09-26

申请号：EP06703258.1

申请日：2006-01-02

申请人： Novartis AG ,  NOVARTIS-PHARMA GMBH

发明人： JAHNKE, Wolfgang ,  RONDEAU, Jean-michel ,  GEISER, Martin ,  RAMAGE, Paul ,  STRAUSS, Andre

IPC分类号： C12N9/10 ,  C30B29/58 ,  C12Q1/48 ,  A61K38/00

CPC分类号： C12N9/1085 ,  C07K2299/00

摘要： The present invention relates to crystalline human farnesyl diphosphate synthase (FPPS), to the three-dimensional structure of free FPPS, as well as the three-dimensional structures of FPPS in complex with substrates such as IPP (isopentenyl diphosphate) and/or with inhibitors, such as Zometa® or Aredia®. Further, methods for preparing crystals of human FPPS are described. According to the invention the crystals can be used to determine the structures of FPPS homologs, mutants, complexes with ligands, FPPS crystal forms and similar molecules of unknown structure. The invention further relates to the use of FPPS crystals to select new FPPS ligands, e.g., by X-ray screening and to design and/or identify inhibitors against FPPS. Furthermore, the invention relates to NMR methods for selecting and/or identifying new low molecular weight binders to FPPS, which represent new therapeutic agents.

公开(公告)号：EP1421383A2

公开(公告)日：2004-05-26

申请号：EP02796261.2

申请日：2002-08-21

申请人： Novartis AG ,  Novartis Pharma GmbH

发明人： FLOERSHEIM, Philipp ,  OSTERMEIER, Christian ,  UZUNOV, Doncho ,  JAHNKE, Wolfgang

IPC分类号： G01N33/50 ,  C12Q1/00

CPC分类号： C12Q1/32 ,  G01N2500/04

摘要： 3 α-hydroxysteroid dehydrogenase (3a-HSD) plays a central role in the metabolism and action of steroid hormones and neurosteroids (steroids synthesized in the central nervous system). The high resolution structure of human type III 3a-HSD crystallized in complex with cofactor NADP is determined by X-ray diffraction. Furthermore the active site is determined. The structure coordinates of the enzyme may be used to design and select novel classes of modulators to human type III 3a-HSD.

公开(公告)号：EP2900637B1

公开(公告)日：2017-08-09

申请号：EP13730654.4

申请日：2013-05-09

申请人： Novartis AG

发明人： FURET, Pascal ,  GROTZFELD, Robert Martin ,  JONES, Darryl Brynley ,  MANLEY, Paul ,  MARZINZIK, Andreas ,  MOUSSAOUI, Saliha ,  PELLE, Xavier Francois Andre ,  SALEM, Bahaa ,  SCHOEPFER, Joseph ,  JAHNKE, Wolfgang

IPC分类号： C07D213/81 ,  C07D213/85 ,  C07D317/60 ,  C07D231/12 ,  C07D233/38 ,  C07D233/54 ,  C07D401/04 ,  C07D239/26 ,  C07D239/30 ,  C07D239/34 ,  C07D407/14 ,  C07D241/12 ,  C07D241/20 ,  C07D277/20 ,  A61K31/505 ,  A61P35/00 ,  A61P31/12 ,  A61P31/14 ,  A61P31/20 ,  A61P25/28

CPC分类号： C07D239/26 ,  A61K31/36 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/426 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/4965 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D213/81 ,  C07D213/85 ,  C07D231/12 ,  C07D233/38 ,  C07D233/54 ,  C07D233/56 ,  C07D239/30 ,  C07D239/34 ,  C07D241/12 ,  C07D241/20 ,  C07D277/22 ,  C07D277/30 ,  C07D317/60 ,  C07D333/22 ,  C07D333/38 ,  C07D401/04 ,  C07D403/04 ,  C07D405/14 ,  C07D407/14 ,  C07D409/06

公开(公告)号：EP2861579B9

公开(公告)日：2018-08-29

申请号：EP13730652.8

申请日：2013-05-09

申请人： Novartis AG

发明人： DODD, Stephanie Kay ,  FURET, Pascal ,  GROTZFELD, Robert Martin ,  JONES, Darryl Brynley ,  MANLEY, Paul ,  MARZINZIK, Andreas ,  PELLE, Xavier Francois Andre ,  SALEM, Bahaa ,  SCHOEPFER, Joseph ,  JAHNKE, Wolfgang

IPC分类号： C07D401/14 ,  C07D401/04 ,  C07D403/10 ,  C07D213/82 ,  A61K31/4439 ,  A61P35/00

CPC分类号： C07D213/82 ,  A61K31/4439 ,  A61K31/506 ,  A61K45/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07F9/58

摘要： The present invention relates to compounds of formula (I): in which Y, Y1, R1, R2, R3 and R4 are defined in the Summary of the Invention; capable of inhibiting the activity of BCR-ABL1 and mutants thereof. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

公开(公告)号：EP2861576B1

公开(公告)日：2018-01-10

申请号：EP13730655.1

申请日：2013-05-09

申请人： Novartis AG

发明人： FURET, Pascal ,  GROTZFELD, Robert Martin ,  JONES, Darryl Brynley ,  MANLEY, Paul ,  MARZINZIK, Andreas ,  PELLE, Xavier Francois Andre ,  SALEM, Bahaa ,  SCHOEPFER, Joseph ,  JAHNKE, Wolfgang

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/5377 ,  A61P31/00

CPC分类号： C07D417/14 ,  A61K31/4025 ,  A61K31/4155 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/10 ,  C07D487/10

摘要： in which Y, Y1, R1, R2, R3 and R4 are defined in the Summary of the Invention; capable of inhibiting the tyrosine kinase enzymatic activity of the Abelson protein (ABL1), the Abelson-related protein (ABL2) and related chimeric proteins, in particular BCR-ABL1. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

公开(公告)号：EP2861579A1

公开(公告)日：2015-04-22

申请号：EP13730652.8

申请日：2013-05-09

申请人： Novartis AG

发明人： DODD, Stephanie Kay ,  FURET, Pascal ,  GROTZFELD, Robert Martin ,  JONES, Darryl Brynley ,  MANLEY, Paul ,  MARZINZIK, Andreas ,  PELLE, Xavier Francois Andre ,  SALEM, Bahaa ,  SCHOEPFER, Joseph ,  JAHNKE, Wolfgang

IPC分类号： C07D401/14 ,  C07D401/04 ,  C07D403/10 ,  C07D213/82 ,  A61K31/4439 ,  A61P35/00

CPC分类号： C07D213/82 ,  A61K31/4439 ,  A61K31/506 ,  A61K45/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07F9/58

摘要： The present invention relates to compounds of formula (I): in which Y, Y1, R1, R2, R3 and R4 are defined in the Summary of the Invention; capable of inhibiting the activity of BCR-ABL1 and mutants thereof. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

摘要翻译： 本发明涉及式（I）的化合物：其中Y，Y 1，R 1，R 2，R 3和R 4在发明概述中定义; 能够抑制BCR-ABL1及其突变体的活性。 本发明进一步提供了制备本发明化合物的方法，包含此类化合物的药物制剂以及使用此类化合物治疗癌症的方法。

公开(公告)号：EP2861579B1

公开(公告)日：2018-02-21

申请号：EP13730652.8

申请日：2013-05-09

申请人： Novartis AG

发明人： DODD, Stephanie Kay ,  FURET, Pascal ,  GROTZFELD, Robert Martin ,  JONES, Darryl Brynley ,  MANLEY, Paul ,  MARZINZIK, Andreas ,  PELLE, Xavier Francois Andre ,  SALEM, Bahaa ,  SCHOEPFER, Joseph ,  JAHNKE, Wolfgang

IPC分类号： C07D401/14 ,  C07D401/04 ,  C07D403/10 ,  C07D213/82 ,  A61K31/4439 ,  A61P35/00

CPC分类号： C07D213/82 ,  A61K31/4439 ,  A61K31/506 ,  A61K45/06 ,  C07D401/04 ,  C07D401/10 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07F9/58

摘要： The present invention relates to compounds of formula (I): in which Y, Y1, R1, R2, R3 and R4 are defined in the Summary of the Invention; capable of inhibiting the activity of BCR-ABL1 and mutants thereof. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

公开(公告)号：EP2900637A1

公开(公告)日：2015-08-05

申请号：EP13730654.4

申请日：2013-05-09

申请人： Novartis AG

发明人： FURET, Pascal ,  GROTZFELD, Robert Martin ,  JONES, Darryl Brynley ,  MANLEY, Paul ,  MARZINZIK, Andreas ,  MOUSSAOUI, Saliha ,  PELLE, Xavier Francois Andre ,  SALEM, Bahaa ,  SCHOEPFER, Joseph ,  JAHNKE, Wolfgang

IPC分类号： C07D213/81 ,  C07D213/85 ,  C07D317/60 ,  C07D231/12 ,  C07D233/38 ,  C07D233/54 ,  C07D401/04 ,  C07D239/26 ,  C07D239/30 ,  C07D239/34 ,  C07D407/14 ,  C07D241/12 ,  C07D241/20 ,  C07D277/20 ,  A61K31/505

CPC分类号： C07D239/26 ,  A61K31/36 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/415 ,  A61K31/4164 ,  A61K31/426 ,  A61K31/4418 ,  A61K31/4439 ,  A61K31/4965 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06 ,  C07D213/81 ,  C07D213/85 ,  C07D231/12 ,  C07D233/38 ,  C07D233/54 ,  C07D233/56 ,  C07D239/30 ,  C07D239/34 ,  C07D241/12 ,  C07D241/20 ,  C07D277/22 ,  C07D277/30 ,  C07D317/60 ,  C07D333/22 ,  C07D333/38 ,  C07D401/04 ,  C07D403/04 ,  C07D405/14 ,  C07D407/14 ,  C07D409/06

摘要： The present invention relates to compounds of formula I: in which Y, Y
1 , Y
4 , Y
5 , Y
6 , R
1 , R
2 , R
3 and R
4 are defined in the Summary of the Invention; capable of inhibiting the activity of BCR-ABL1 and mutants thereof. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

摘要翻译： 本发明涉及式I的化合物：其中Y，Y1，Y4，Y5，Y6，R1，R2，R3和R4在发明概述中所定义; 能够抑制BCR-ABL1和其突变体的活性。 本发明进一步提供了一种用于本发明的化合物的制备方法，药物制剂，其包括测试的化合物，并使用在癌症的治疗中搜索化合物的方法。

公开(公告)号：EP2225252B1

公开(公告)日：2012-06-27

申请号：EP08854485.3

申请日：2008-11-26

申请人： Novartis AG

发明人： WEILER, Sven ,  WIDLER, Leo ,  RONDEAU, Jean-Michel ,  COTESTA, Simona ,  JAHNKE, Wolfgang

IPC分类号： C07F9/6506 ,  A61K31/663 ,  A61P19/00

CPC分类号： C07F9/65061

摘要： C2-C5-Alkyl-substituted [(imidazol-1 -yl)-1-hydroxy-1-phosphono-ethyl]-phosphonic acids, as well as methods or processes for their manufacture, their use in the manufacture of pharmaceutical formulations, their use in the treatment of diseases, methods of using them in the treatment of diseases, pharmaceutical formulations encompassing them and/or the compounds for use in the treatment of diseases, are described. The compounds are able to inhibit excessive or inappropriate bone resorption and for the treatment of other diseases which are caused by excessive prenylation of target proteins, such as Hutchinson-Gilford progeria syndrome. The compounds are of the formula (I), wherein one of R1 and R2 is hydrogen and the other is C2-C5-alkyl that is branched or unbranched, and can be in free form, in the form of an ester, and/or of a salt.

公开(公告)号：EP2861576A1

公开(公告)日：2015-04-22

申请号：EP13730655.1

申请日：2013-05-09

申请人： Novartis AG

发明人： FURET, Pascal ,  GROTZFELD, Robert Martin ,  JONES, Darryl Brynley ,  MANLEY, Paul ,  MARZINZIK, Andreas ,  PELLE, Xavier Francois Andre ,  SALEM, Bahaa ,  SCHOEPFER, Joseph ,  JAHNKE, Wolfgang

IPC分类号： C07D401/04 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/10 ,  C07D417/14 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/496 ,  A61K31/5377 ,  A61P31/00

CPC分类号： C07D417/14 ,  A61K31/4025 ,  A61K31/4155 ,  A61K31/427 ,  A61K31/4439 ,  A61K31/5377 ,  A61K45/06 ,  C07D401/04 ,  C07D401/14 ,  C07D403/10 ,  C07D405/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/10 ,  C07D487/10

摘要： in which Y, Y1, R1, R2, R3 and R4 are defined in the Summary of the Invention; capable of inhibiting the tyrosine kinase enzymatic activity of the Abelson protein (ABL1), the Abelson-related protein (ABL2) and related chimeric proteins, in particular BCR-ABL1. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

摘要翻译： 本发明涉及式（I）的化合物：其中Y，Y，R，R 2，R 3和R 4在发明内容中定义; 能够抑制Abelson蛋白（ABL1），Abelson相关蛋白（ABL2）和相关嵌合蛋白，特别是BCR-ABL1的酪氨酸激酶酶活性。 本发明进一步提供了制备本发明化合物的方法，包含此类化合物的药物制剂以及使用此类化合物治疗癌症的方法。