公开(公告)号：WO2010080503A1

公开(公告)日：2010-07-15

申请号：PCT/US2009/068496

申请日：2009-12-17

Applicant: GENENTECH, INC. ,  THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH ,  ABBOTT LABORATORIES ,  BAELL, Jonathon, Bayldon ,  BUI, Chinh, Thien ,  COLMAN, Peter ,  CZABOTAR, Peter ,  DUDLEY, Danette, A. ,  FAIRBROTHER, Wayne, J. ,  FLYGARE, John, A. ,  LASSENE, Guillaume, Laurent ,  NDUBAKU, Chudi ,  NIKOLAKOPOULOS, George ,  SLEEBS, Brad, Edmund ,  SMITH, Brian, John ,  WATSON, Keith, Geoffrey ,  ELMORE, Steven, W. ,  HASVOLD, Lisa, A. ,  PETROS, Andrew, M. ,  SOUERS, Andrew, J. ,  TAO, Zhi-Fu ,  WANG, Le ,  WANG, Xilu ,  DESHAYES, Kurt

Inventor： BAELL, Jonathon, Bayldon ,  BUI, Chinh, Thien ,  COLMAN, Peter ,  CZABOTAR, Peter ,  DUDLEY, Danette, A. ,  FAIRBROTHER, Wayne, J. ,  FLYGARE, John, A. ,  LASSENE, Guillaume, Laurent ,  NDUBAKU, Chudi ,  NIKOLAKOPOULOS, George ,  SLEEBS, Brad, Edmund ,  SMITH, Brian, John ,  WATSON, Keith, Geoffrey ,  ELMORE, Steven, W. ,  HASVOLD, Lisa, A. ,  PETROS, Andrew, M. ,  SOUERS, Andrew, J. ,  TAO, Zhi-Fu ,  WANG, Le ,  WANG, Xilu ,  DESHAYES, Kurt

IPC: A01N43/00

CPC classification number: C07D417/14 ,  C07D471/06 ,  C07D473/00 ,  C07D487/04 ,  C07D495/04 ,  C07D513/04 ,  C07D513/06

Abstract: In one aspect, the present invention provides for a compound of Formula I; in which the variable X 1a , X 1b , X 1c , X 1d , Q, A, R 1 , B, L, E, and the subscripts m and n have the meanings as described herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula I as well as methods for using compounds of Formula I for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-x L proteins.

Abstract translation: 一方面，本发明提供式I的化合物; 其中变量X1a，X1b，X1c，X1d，Q，A，R1，B，L，E和下标m和n具有如本文所述的含义。 另一方面，本发明提供包含式I化合物的药物组合物以及使用式I化合物治疗以表达或过表达为特征的疾病和病症（例如癌症，血小板增多症等）的方法 的Bcl-2抗凋亡蛋白，例如抗凋亡Bcl-xL蛋白。

公开(公告)号：WO2010065865A2

公开(公告)日：2010-06-10

申请号：PCT/US2009/066790

申请日：2009-12-04

Applicant: ABBOTT LABORATORIES ,  BRUNCKO, Milan ,  DING, Hong ,  DOHERTY, George, A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron, R. ,  MANTEI, Robert, A. ,  MCCLELLAN, William, J. ,  PARK, Chang, H. ,  PARK, Cheol-min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D.

Inventor： BRUNCKO, Milan ,  DING, Hong ,  DOHERTY, George, A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron, R. ,  MANTEI, Robert, A. ,  MCCLELLAN, William, J. ,  PARK, Chang, H. ,  PARK, Cheol-min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D.

IPC: C07D405/12 ,  A61K31/404 ,  A61P35/00

CPC classification number: C07D405/12 ,  C07D209/32 ,  C07D211/96 ,  C07D213/64 ,  C07D215/20 ,  C07D217/16 ,  C07D231/56 ,  C07D235/26 ,  C07D249/04 ,  C07D295/125 ,  C07D295/14 ,  C07D309/14 ,  C07D401/12 ,  C07D417/12

Abstract: Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 or Bcl-xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti-apoptotic Bcl-2 protein.

Abstract translation: 公开了抑制抗凋亡Bcl-2或Bcl-xL蛋白的活性的化合物，含有该化合物的组合物和治疗疾病的方法，其中表达抗凋亡Bcl-2蛋白。

公开(公告)号：WO2010065824A2

公开(公告)日：2010-06-10

申请号：PCT/US2009/066722

申请日：2009-12-04

Applicant: ABBOTT LABORATORIES ,  BRUNCKO, Milan ,  DAI, Yujia ,  DING, Hong ,  DOHERTY, George, A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron, R. ,  MANTEI, Robert, A. ,  MCCLELLAN, William, J. ,  PARK, Chang, H. ,  PARK, Cheol-Min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-Fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D.

Inventor： BRUNCKO, Milan ,  DAI, Yujia ,  DING, Hong ,  DOHERTY, George, A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron, R. ,  MANTEI, Robert, A. ,  MCCLELLAN, William, J. ,  PARK, Chang, H. ,  PARK, Cheol-Min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-Fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D.

IPC: A61P35/00 ,  A61K31/496 ,  C07D403/12

CPC classification number: C07D405/12 ,  C07D209/08 ,  C07D211/58 ,  C07D213/74 ,  C07D213/84 ,  C07D231/56 ,  C07D235/06 ,  C07D277/24 ,  C07D295/30 ,  C07D309/04 ,  C07D401/14 ,  C07D405/14 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04

Abstract: Disclosed are compounds which inhibit the activity of anti-apoptotic Bcl-2 proteins, compositions containing the compounds and methods of treating diseases during which is expressed anti-apoptotic Bcl-2 protein.

Abstract translation: 公开了抑制抗凋亡Bcl-2蛋白活性的化合物，含有化合物的组合物和治疗疾病的方法，其中表达抗凋亡Bcl-2蛋白。

公开(公告)号：WO2011068561A1

公开(公告)日：2011-06-09

申请号：PCT/US2010/036919

申请日：2010-06-01

Applicant: ABBOTT LABORATORIES ,  BRUNCKO, Milan ,  DING, Hong ,  DOHERTY, George A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron ,  MANTEI, Robert, A. ,  McCLELLAN, William, J. ,  PARK, Chang, H. ,  PARK, Cheol-Min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-Fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D. ,  HANSEN, Todd, M.

Inventor： BRUNCKO, Milan ,  DING, Hong ,  DOHERTY, George A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron ,  MANTEI, Robert, A. ,  McCLELLAN, William, J. ,  PARK, Chang, H. ,  PARK, Cheol-Min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-Fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D. ,  HANSEN, Todd, M.

IPC: C07D405/12 ,  A61K31/404 ,  A61P35/00 ,  C07D209/32 ,  C07D211/96 ,  C07D213/64 ,  C07D215/20 ,  C07D217/16 ,  C07D235/26 ,  C07D249/04 ,  C07D295/14 ,  C07D309/14 ,  C07D401/12 ,  C07D295/125 ,  C07D231/56 ,  C07D405/14

CPC classification number: C07D401/12 ,  A61K31/407 ,  A61K31/495 ,  A61K31/496 ,  A61K31/501 ,  A61K31/5377 ,  A61K45/06 ,  C07D209/08 ,  C07D209/32 ,  C07D211/58 ,  C07D211/96 ,  C07D213/64 ,  C07D215/20 ,  C07D217/16 ,  C07D231/56 ,  C07D235/26 ,  C07D241/04 ,  C07D249/04 ,  C07D295/125 ,  C07D295/14 ,  C07D295/155 ,  C07D309/04 ,  C07D309/14 ,  C07D401/06 ,  C07D403/06 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D413/06 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04

Abstract: Disclosed are compounds (I) which inhibit the activity of anti-apoptotic Bc1-2 or Bc1 xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti apoptotic Bc1-2 protein.

Abstract translation: 公开了抑制抗凋亡Bc1-2或Bc1 xL蛋白活性的化合物（I），含有该化合物的组合物和治疗其中表达抗凋亡Bc1-2蛋白的疾病的方法。

公开(公告)号：WO2010080478A1

公开(公告)日：2010-07-15

申请号：PCT/US2009/068400

申请日：2009-12-17

Applicant: GENENTECH, INC. ,  THE WALTER AND ELIZA HALL INSTITUTE OF MEDICAL RESEARCH ,  ABBOTT LABORATORIES ,  BAELL, Jonathon, Bayldon ,  BUI, Chinh, Thien ,  COLMAN, Peter ,  DUDLEY, Danette, A. ,  FAIRBROTHER, Wayne, J. ,  FLYGARE, John, A. ,  LASSENE, Guillaume, Laurent ,  NDUBAKU, Chudi ,  NIKOLAKOPOULOS, George ,  RYE, Carl, Steven ,  SLEEBS, Brad, Edmund ,  SMITH, Brian, John ,  WATSON, Keith, Geoffrey ,  ELMORE, Steven, W. ,  PETROS, Andrew, M. ,  SOUERS, Andrew, J.

Inventor： BAELL, Jonathon, Bayldon ,  BUI, Chinh, Thien ,  COLMAN, Peter ,  DUDLEY, Danette, A. ,  FAIRBROTHER, Wayne, J. ,  FLYGARE, John, A. ,  LASSENE, Guillaume, Laurent ,  NDUBAKU, Chudi ,  NIKOLAKOPOULOS, George ,  RYE, Carl, Steven ,  SLEEBS, Brad, Edmund ,  SMITH, Brian, John ,  WATSON, Keith, Geoffrey ,  ELMORE, Steven, W. ,  PETROS, Andrew, M. ,  SOUERS, Andrew, J.

IPC: A61K31/535

CPC classification number: C07D417/14 ,  C07D417/12 ,  C07D487/04

Abstract: In one aspect, the present invention provides for a compound of Formula (I) in which, the variables X 1 , X 2a , X 2b , X 2c , R 1 , B, L, E, A and the subscript n are as defined herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula (I) as well as methods for using compounds of Formula (I) for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-x L proteins.

Abstract translation: 一方面，本发明提供式（I）的化合物，其中变量X1，X2a，X2b，X2c，R1，B，L，E，A和下标n如本文所定义。 在另一方面，本发明提供包含式（I）化合物的药物组合物以及使用式（I）化合物治疗由表达特征的疾病和病症（例如癌症，血小板增多症等）的方法 或过度表达Bcl-2抗凋亡蛋白，例如抗凋亡Bcl-xL蛋白。

公开(公告)号：EP2507229A1

公开(公告)日：2012-10-10

申请号：EP10727241.1

申请日：2010-06-01

Applicant: Abbott Laboratories

Inventor： PARK, Chang, H. ,  BRUNCKO, Milan ,  DING, Hong ,  DOHERTY, George A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron ,  MANTEI, Robert, A. ,  McCLELLAN, William, J. ,  PARK, Cheol-Min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-Fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D. ,  HANSEN, Todd, M.

IPC: C07D405/12 ,  A61K31/404 ,  A61P35/00 ,  C07D209/32 ,  C07D211/96 ,  C07D213/64 ,  C07D215/20 ,  C07D217/16 ,  C07D235/26 ,  C07D249/04 ,  C07D295/14 ,  C07D309/14 ,  C07D401/12 ,  C07D295/125 ,  C07D231/56 ,  C07D405/14

CPC classification number: C07D401/12 ,  A61K31/407 ,  A61K31/495 ,  A61K31/496 ,  A61K31/501 ,  A61K31/5377 ,  A61K45/06 ,  C07D209/08 ,  C07D209/32 ,  C07D211/58 ,  C07D211/96 ,  C07D213/64 ,  C07D215/20 ,  C07D217/16 ,  C07D231/56 ,  C07D235/26 ,  C07D241/04 ,  C07D249/04 ,  C07D295/125 ,  C07D295/14 ,  C07D295/155 ,  C07D309/04 ,  C07D309/14 ,  C07D401/06 ,  C07D403/06 ,  C07D405/06 ,  C07D405/12 ,  C07D405/14 ,  C07D413/06 ,  C07D417/12 ,  C07D471/04 ,  C07D487/04

Abstract: Disclosed are compounds (I) which inhibit the activity of anti-apoptotic Bc1-2 or Bc1 xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti apoptotic Bc1-2 protein.

公开(公告)号：EP1337555A2

公开(公告)日：2003-08-27

申请号：EP01987213.4

申请日：2001-11-15

Applicant: ABBOTT LABORATORIES

Inventor： FESIK, Stephen, W. ,  PETROS, Andrew, M. ,  YOON, HoSup ,  NETTESHEIM, David, G.

IPC: C07K14/47

CPC classification number: C07K14/4747

Abstract: Mutant peptides derived from wild-type human Bcl-2 are disclosed. Assays to identify substances which block the ability of Bcl-2 to inhibit apoptosis also are disclosed.

公开(公告)号：EP2376085A1

公开(公告)日：2011-10-19

申请号：EP09837907.6

申请日：2009-12-17

Applicant: Genentech, Inc. ,  The Walter and Eliza Hall Institute of Medical Research ,  Abbott Laboratories

Inventor： BAELL, Jonathan, Bayldon ,  BUI, Chinh, Thien ,  COLMAN, Peter ,  DUDLEY, Danette, A. ,  FAIRBROTHER, Wayne, J. ,  FLYGARE, John, A. ,  LESSENE, Guillaume, Laurent ,  NDUBAKU, Chudi ,  NIKOLAKOPOULOS, George ,  RYE, Carl, Steven ,  SLEEBS, Brad, Edmund ,  SMITH, Brian, John ,  WATSON, Keith, Geoffrey ,  ELMORE, Steven, W. ,  PETROS, Andrew, M. ,  SOUERS, Andrew, J. ,  CZABOTAR, Peter

IPC: A61K31/535

CPC classification number: C07D417/14 ,  C07D417/12 ,  C07D487/04

Abstract: In one aspect, the present invention provides for a compound of Formula (I) in which, the variables X
1 , X
2a , X
2b , X
2c , R
1 , B, L, E, A and the subscript n are as defined herein. In another aspect, the present invention provides for pharmaceutical compositions comprising compounds of Formula (I) as well as methods for using compounds of Formula (I) for the treatment of diseases and conditions (e.g., cancer, thrombocythemia, etc) characterized by the expression or over-expression of Bcl-2 anti-apoptotic proteins, e.g., of anti-apoptotic Bcl-x
L proteins.

公开(公告)号：EP1318978B1

公开(公告)日：2006-02-08

申请号：EP01971244.7

申请日：2001-09-20

Applicant: ABBOTT LABORATORIES

Inventor： MCCLELLAN, William ,  OOST, Thorsten ,  BRUNCKO, Milan ,  WANG, Xilu ,  AUGERI, David, J. ,  BAUMEISTER, Steven, A. ,  DICKMAN, Daniel, A. ,  DING, Hong ,  DINGES, Jurgen ,  FESIK, Stephen, W. ,  HAJDUK, Philip, J. ,  KUNZER, Aaron, R. ,  NETTESHEIM, David, G. ,  PETROS, Andrew, M. ,  ROSENBERG, Saul, H. ,  SHEN, Wang ,  THOMAS, Sheela, A. ,  WENDT, Michael, D.

IPC: C07C311/51 ,  C07C317/28 ,  C07C323/12 ,  C07C323/17 ,  C07C323/25 ,  C07C323/30 ,  C07C323/37 ,  C07C323/58 ,  C07C323/60 ,  C07D209/08 ,  C07D209/96 ,  C07D213/61 ,  C07D213/70 ,  C07D215/48 ,  C07D221/20 ,  C07D263/56 ,  C07D277/62 ,  C07D277/64 ,  C07D295/14 ,  C07D295/20 ,  C07D333/28

CPC classification number: C07D207/404 ,  C07C311/51 ,  C07C317/28 ,  C07C323/12 ,  C07C323/17 ,  C07C323/25 ,  C07C323/30 ,  C07C323/37 ,  C07C323/58 ,  C07C323/60 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/16 ,  C07C2601/18 ,  C07C2602/08 ,  C07C2602/10 ,  C07C2602/28 ,  C07C2602/42 ,  C07C2602/44 ,  C07C2603/74 ,  C07D203/10 ,  C07D205/12 ,  C07D207/24 ,  C07D209/08 ,  C07D209/96 ,  C07D211/44 ,  C07D211/70 ,  C07D211/74 ,  C07D213/61 ,  C07D213/70 ,  C07D213/71 ,  C07D215/14 ,  C07D215/227 ,  C07D215/48 ,  C07D217/04 ,  C07D221/20 ,  C07D231/12 ,  C07D235/08 ,  C07D235/26 ,  C07D241/16 ,  C07D249/04 ,  C07D263/56 ,  C07D263/58 ,  C07D277/62 ,  C07D277/64 ,  C07D295/13 ,  C07D295/155 ,  C07D295/185 ,  C07D295/205 ,  C07D295/215 ,  C07D295/26 ,  C07D307/14 ,  C07D317/54 ,  C07D333/28 ,  C07D333/68 ,  C07D401/06 ,  C07D401/12 ,  C07D405/04 ,  C07D417/12 ,  C07D451/02

Abstract: N-Benzoyl arylsulfonamides having the formula (I) are BCL-Xl inhibitors and are useful for promoting apoptosis. Also disclosed are BCL-Xl inhibiting compositions and methods of promoting apoptosis in a mammal.

公开(公告)号：EP2376480A2

公开(公告)日：2011-10-19

申请号：EP09795606.4

申请日：2009-12-04

Applicant: Abbott Laboratories

Inventor： BRUNCKO, Milan ,  DING, Hong ,  DOHERTY, George, A. ,  ELMORE, Steven, W. ,  HASVOLD, Lisa ,  HEXAMER, Laura ,  KUNZER, Aaron, R. ,  MANTEI, Robert, A. ,  MCCLELLAN, William, J. ,  PARK, Chang, H. ,  PARK, Cheol-min ,  PETROS, Andrew, M. ,  SONG, Xiaohong ,  SOUERS, Andrew, J. ,  SULLIVAN, Gerard, M. ,  TAO, Zhi-fu ,  WANG, Gary, T. ,  WANG, Le ,  WANG, Xilu ,  WENDT, Michael, D.

IPC: C07D405/12 ,  A61K31/404 ,  A61P35/00

CPC classification number: C07D405/12 ,  C07D209/32 ,  C07D211/96 ,  C07D213/64 ,  C07D215/20 ,  C07D217/16 ,  C07D231/56 ,  C07D235/26 ,  C07D249/04 ,  C07D295/125 ,  C07D295/14 ,  C07D309/14 ,  C07D401/12 ,  C07D417/12

Abstract: Disclosed are compounds of formula (I) which inhibit the activity of anti-apoptotic BcI -2 or BcI -xL proteins, compositions containing the compounds and methods of treating diseases during which are expressed anti -aooptotic Bcl-2 protein.