公开(公告)号：EP2349997B1

公开(公告)日：2015-08-12

申请号：EP09737501.8

申请日：2009-10-07

申请人： Exelixis, Inc. ,  Daiichi Sankyo Company, Limited

发明人： NUSS, John ,  WILLIAMS, Matthew ,  MOHAN, Raju ,  MARTIN, Richard ,  WANG, Tie-Lin ,  AOKI, Kazumasa ,  TSURUOKA, Hiroyuki ,  HAYASHI, Noriyuki ,  HOMMA, Tsuyoshi

IPC分类号： C07D207/34 ,  A61K31/40 ,  A61P9/00

CPC分类号： C07D207/34

公开(公告)号：EP2349996B1

公开(公告)日：2014-01-01

申请号：EP09793339.4

申请日：2009-10-07

申请人： Exelixis, Inc. ,  Daiichi Sankyo Company, Limited

发明人： NUSS, John ,  WILLIAMS, Matthew ,  MOHAN, Raju ,  MARTIN, Richard ,  WANG, Tie-lin ,  TSURUOKA, Hiroyuki ,  AOKI, Kazumasa ,  HONZUMI, Masatoshi ,  ASOH, Yusuke ,  SAITO, Keiji ,  HOMMA, Tsuyoshi

IPC分类号： C07D207/34 ,  C07D207/335 ,  A61K31/405 ,  A61P9/12 ,  A61P9/10 ,  A61P13/12 ,  A61P5/42 ,  A61P7/10

CPC分类号： C07D207/34

公开(公告)号：EP2349996A1

公开(公告)日：2011-08-03

申请号：EP09793339.4

申请日：2009-10-07

申请人： Exelixis, Inc. ,  Daiichi Sankyo Company, Limited

发明人： NUSS, John ,  WILLIAMS, Matthew ,  MOHAN, Raju ,  MARTIN, Richard ,  WANG, Tie-lin ,  TSURUOKA, Hiroyuki ,  AOKI, Kazumasa ,  HONZUMI, Masatoshi ,  ASOH, Yusuke ,  SAITO, Keiji ,  HOMMA, Tsuyoshi

IPC分类号： C07D207/335 ,  A61K31/405 ,  A61P9/12 ,  A61P9/10 ,  A61P13/12 ,  A61P5/42 ,  A61P7/10

CPC分类号： C07D207/34

摘要： The present invention comprises a compound for the prevention and/or treatment of cardiovascular diseases, nephropathy, fibrosis, primary aldosteronism or edema. The compound is of the following general formula (I): wherein R
1 represents a C1 -C3 alkyl group; R
2 represents a hydroxy -C1 -C4 alkyl group and the like; R
3 represents a halogeno group, a halogeno-C1 -C3 alkyl group and the like; R
4 represents a hydrogen atom, a halogeno group and the like,- R
5 represents a sulfamoyl group or a C1-C3 alkylsulf onyl group; R
6 represents a hydrogen atom, a halogeno group and the like] or an N-oxide, atropisomer of the foregoing, or pharmaceutically acceptable salt of the foregoing.

摘要翻译： 本发明包含用于预防和/或治疗心血管疾病，肾病，纤维化，原发性醛固酮增多症或水肿的化合物。 该化合物具有以下通式（I）：其中R 1代表C 1 -C 3烷基; R 2表示羟基-C 1 -C 4烷基等; R 3表示卤代基，卤代-C 1 -C 3烷基等; R 4表示氢原子，卤代基等，-R 5表示氨磺酰基或C 1 -C 3烷基磺酰基， R 6表示氢原子，卤代基等]或前述的N-氧化物，阻转异构体或前述的药学上可接受的盐。

公开(公告)号：EP1841760A2

公开(公告)日：2007-10-10

申请号：EP05855893.3

申请日：2005-12-28

申请人： Exelixis, Inc.

发明人： CHEN, Jeff ,  DALRYMPLE, Lisa, Esther ,  EPSHTEYN, Sergey ,  FORSYTH, Timothy, Patrick ,  HUYNH, Tai, Phat ,  IBRAHIM, Mohamed, Abdulkader ,  LEAHY, James, W. ,  LEWIS, Gary, Lee ,  MANN, Grace ,  MANN, Lary, W. ,  NOGUCHI, Robin, Tammie ,  RIDGWAY, Brian, Hugh ,  SANGALANG, Joan, Cruz ,  SCHNEPP, Kevin, Luke ,  SHI, Xian ,  TAKEUCHI, Craig, Stacy ,  WILLIAMS, Matthew, Alan ,  NUSS, John ,  CHEUNG, Atwood, K.

IPC分类号： C07D403/14 ,  C07D401/12 ,  C07D413/14 ,  A61K31/495 ,  A61K31/42 ,  A61P35/00 ,  A61P29/00

CPC分类号： C07D413/14 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/14 ,  C07D487/04

摘要： The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wild­type Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a farmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NR1R1a, or O-R1, wherein X is H, halo, C1-C6 alkyl, NO2, mono-, di-, or tri-halo substituted methyl, NR13R,14. C(O)O-C1-C6 alkyl, or N(R13)-C(O)-C1-C6 alkyl; Y is H, halo, OH, C1-C6 alkyl, C0-C6 alkyl-NR,15R16, NRI5R,6, C1-C6 alkoxy, -N(R13)-(CH2)n-­NR15R16, -C(O)O-C1-C6 alkyl, -O-(CH2)n-NR15R16, -C(O)-C1-C6 alkyl, -C0-C6-alkyl-R21, -O-R21, -C(O)-R21, -O-(CH2)n-R21, -C(O)-NR13R14, -C(O)-N(R13)-aryl, -C(O)-N(R13)­(CH2)n-NR15R16, -C(O)-N(R13)-(CH2)n-aryl -C(O)-N(R13)-(CH2)n-heterocyclyl; or X and Y together with the atoms to which they are attached form a 4-7 membered heterocyclyl or heteroaryl group containing one or two heteroatoms independently selected from O, N, and S. Z is H, NR2R3, -S-R2a, or -0-R2a

公开(公告)号：EP1848719A1

公开(公告)日：2007-10-31

申请号：EP05855490.8

申请日：2005-12-27

申请人： Exelixis, Inc.

发明人： RICE, Kenneth, D. ,  CO, Erick, Wang ,  KIM, Moon, Hwan ,  BANNEN, Lynn, Canne ,  BUSSENIUS, Joerg ,  LE, Donna ,  TSUHAKO, Amy, Lew ,  NUSS, John ,  WANG, Yong ,  XU, Wei ,  KLEIN, Rhett, Ronald

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P35/00 ,  A61P29/00 ,  A61P37/00

CPC分类号： C07D487/04

摘要： The invention provides compounds of formula (I) and methods for inhibition of kinases, more specifically p70S6 kinases, and more preferably p70S6, Akt-1 and Akt-2 kinases. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration, chemoinvasion and metabolism. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions.

公开(公告)号：EP1848719B1

公开(公告)日：2012-02-01

申请号：EP05855490.8

申请日：2005-12-27

申请人： Exelixis, Inc.

发明人： RICE, Kenneth, D. ,  CO, Erick, Wang ,  KIM, Moon, Hwan ,  BANNEN, Lynn, Canne ,  BUSSENIUS, Joerg ,  LE, Donna ,  TSUHAKO, Amy, Lew ,  NUSS, John ,  WANG, Yong ,  XU, Wei ,  KLEIN, Rhett, Ronald

IPC分类号： C07D487/04 ,  A61K31/519 ,  A61P35/00 ,  A61P29/00 ,  A61P37/00

CPC分类号： C07D487/04

摘要： The invention provides compounds of formula (I) and methods for inhibition of kinases, more specifically p70S6 kinases, and more preferably p70S6, Akt-1 and Akt-2 kinases. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration, chemoinvasion and metabolism. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions.

公开(公告)号：EP1841760B1

公开(公告)日：2011-08-10

申请号：EP05855893.3

申请日：2005-12-28

申请人： Exelixis, Inc.

发明人： CHEN, Jeff ,  DALRYMPLE MEYR, Lisa, Esther ,  EPSHTEYN, Sergey ,  FORSYTH, Timothy, Patrick ,  HUYNH, Tai, Phat ,  IBRAHIM, Mohamed, Abdulkader ,  LEAHY, James, W. ,  LEWIS, Gary, Lee ,  MANN, Grace ,  MANN, Larry, W. ,  NOGUCHI, Robin, Tammie ,  RIDGWAY, Brian, Hugh ,  SANGALANG, Joan, Cruz ,  SCHNEPP, Kevin, Luke ,  SHI, Xian ,  TAKEUCHI, Craig, Stacy ,  WILLIAMS, Matthew, Alan ,  NUSS, John ,  CHEUNG, Atwood, K.

IPC分类号： C07D403/14 ,  C07D401/12 ,  C07D413/14 ,  A61K31/495 ,  A61K31/42 ,  A61P35/00 ,  A61P29/00

CPC分类号： C07D413/14 ,  C07D239/48 ,  C07D401/14 ,  C07D403/12 ,  C07D405/14 ,  C07D413/04 ,  C07D413/12 ,  C07D417/14 ,  C07D487/04

摘要： The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wild­type Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a farmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NR1R1a, or O-R1, wherein X is H, halo, C1-C6 alkyl, NO2, mono-, di-, or tri-halo substituted methyl, NR13R,14. C(O)O-C1-C6 alkyl, or N(R13)-C(O)-C1-C6 alkyl; Y is H, halo, OH, C1-C6 alkyl, C0-C6 alkyl-NR,15R16, NRI5R,6, C1-C6 alkoxy, -N(R13)-(CH2)n-­NR15R16, -C(O)O-C1-C6 alkyl, -O-(CH2)n-NR15R16, -C(O)-C1-C6 alkyl, -C0-C6-alkyl-R21, -O-R21, -C(O)-R21, -O-(CH2)n-R21, -C(O)-NR13R14, -C(O)-N(R13)-aryl, -C(O)-N(R13)­(CH2)n-NR15R16, -C(O)-N(R13)-(CH2)n-aryl -C(O)-N(R13)-(CH2)n-heterocyclyl; or X and Y together with the atoms to which they are attached form a 4-7 membered heterocyclyl or heteroaryl group containing one or two heteroatoms independently selected from O, N, and S. Z is H, NR2R3, -S-R2a, or -0-R2a

公开(公告)号：EP2349997A1

公开(公告)日：2011-08-03

申请号：EP09737501.8

申请日：2009-10-07

申请人： Exelixis, Inc. ,  Daiichi Sankyo Company, Limited

发明人： NUSS, John ,  WILLIAMS, Matthew ,  MOHAN, Raju ,  MARTIN, Richard ,  WANG, Tie-Lin ,  AOKI, Kazumasa ,  TSURUOKA, Hiroyuki ,  HAYASHI, Noriyuki ,  HOMMA, Tsuyoshi

IPC分类号： C07D207/34 ,  A61K31/40 ,  A61P9/00

CPC分类号： C07D207/34

摘要： The present invention comprises a compound for the prevention and/or treatment of cardiovascular diseases. The compound is an atropisomer of a compound represented by the following general formula (I ) : wherein R
1 represents a C1-C3 alkyl group; R
2 represents a 2-hydroxy- C4-C6 alkyl group; R
3 represents a halogeno group, a halogeno-C1-C3 alkyl group and the like; R
4 represents a hydrogen atom, a halogeno group and the like; R
5 represents a C1-C3 alkyl group; and R
6 represents a hydrogen atom, a halogeno group and the like] or atropisomers thereof.

公开(公告)号：EP1610774A2

公开(公告)日：2006-01-04

申请号：EP04749893.6

申请日：2004-04-08

申请人： Exelixis, Inc.

发明人： IBRAHIM, Mohamed ,  LEAHY, James ,  SANGALANG, Joan, C. ,  SCHNEPP, Kevin ,  SHI, Xian ,  NUSS, John

IPC分类号： A61K31/395 ,  A61K31/505 ,  C07D239/95 ,  C07D215/16 ,  C07D401/04 ,  C07D401/06 ,  C07D405/04 ,  C07D409/04 ,  C07D413/14 ,  C07D401/14 ,  C07D409/14

CPC分类号： C07D239/94 ,  C07D401/04 ,  C07D405/04

摘要： A compound according to Formula IV: or a pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and methods of use thereof, wherein R1, R2, R3, R4, R5 and X are as defined in the specification.