公开(公告)号：US20100056517A1

公开(公告)日：2010-03-04

申请号：US12513835

申请日：2007-11-15

申请人： Jonathan Bayldon Baell ,  Guillaume Laurent Lessene ,  Brad Edmund Sleebs ,  Wayne J. Fairbrother ,  John A. Flygare ,  Michael F.T. Koeler

发明人： Jonathan Bayldon Baell ,  Guillaume Laurent Lessene ,  Brad Edmund Sleebs ,  Wayne J. Fairbrother ,  John A. Flygare ,  Michael F.T. Koeler

IPC分类号： A61K31/5377 ,  A61K31/496 ,  C07D413/14 ,  C07D239/86 ,  A61P35/00

CPC分类号： C07D239/94

摘要： The invention relates generally to small molecules that mimic the biological activity of certain peptides and proteins, to compositions containing them and to their use. In particular, the invention relates to compounds of the general formula (I) that mimic the biological activity of BH3-only proteins and are capable of binding to and neutralizing pro-survival Bcl-2 proteins: wherein A1, A2, B1, B2, B3, X, Z, R1, R2, R3 and t are as described herein. The invention also relates to processes of preparing the benzenesulfonamide compounds that mimic portions of peptides and proteins, and to the use of such compounds in the regulation of cell death and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death.

摘要翻译： 本发明一般涉及模拟某些肽和蛋白质的生物学活性的小分子，含有它们的组合物及其用途。 特别地，本发明涉及模拟仅含BH3蛋白的生物学活性的通式（I）的化合物，并能够结合并中和原生存Bcl-2蛋白：其中A1，A2，B1，B2， B3，X，Z，R1，R2，R3和t如本文所述。 本发明还涉及制备模仿肽和蛋白质的一部分的苯磺酰胺化合物的方法，以及这些化合物在调节细胞死亡中的用途以及治疗和/或预防与细胞死亡调节相关的疾病或病症 。

公开(公告)号：US20100190782A1

公开(公告)日：2010-07-29

申请号：US12641063

申请日：2009-12-17

申请人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers

发明人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers

IPC分类号： A61K31/536 ,  C07D417/14 ,  A61K31/4709 ,  C07D487/04 ,  A61K31/519 ,  A61K31/502 ,  A61K31/428 ,  A61K31/5377 ,  A61P35/02 ,  A61P35/00 ,  A61P7/02 ,  A61P9/00

CPC分类号： C07D417/14 ,  C07D417/12 ,  C07D487/04

摘要： In one aspect, the present invention provides for a compound of Formula I in which in Formula I, the variables X1, X2a, X2b, X2c, R1, 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-xL proteins.

摘要翻译： 一方面，本发明提供式I化合物，其中在式I中，变量X1，X2a，X2b，X2c，R1，B，L，E，A和下标n如本文所定义。 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：US20120184541A1

公开(公告)日：2012-07-19

申请号：US13347364

申请日：2012-01-10

申请人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers ,  Peter Czabotar

发明人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers ,  Peter Czabotar

IPC分类号： A61K31/4709 ,  A61K31/519 ,  A61P9/00 ,  A61P35/00 ,  A61P35/02 ,  A61P7/02 ,  A61K31/538 ,  A61K31/498

CPC分类号： C07D417/14 ,  C07D417/12 ,  C07D487/04

摘要： In one aspect, the present invention provides for a compound of Formula I in which in Formula I, the variables X1, X2a, X2b, X2c, R1, 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-xL proteins.

摘要翻译： 一方面，本发明提供式I化合物，其中在式I中，变量X1，X2a，X2b，X2c，R1，B，L，E，A和下标n如本文所定义。 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：US08168645B2

公开(公告)日：2012-05-01

申请号：US12513835

申请日：2007-11-15

申请人： Jonathan Bayldon Baell ,  Guillaume Laurent Lessene ,  Brad Edmund Sleebs ,  Wayne J. Fairbrother ,  John A. Flygare ,  Michael F. T. Koehler

发明人： Jonathan Bayldon Baell ,  Guillaume Laurent Lessene ,  Brad Edmund Sleebs ,  Wayne J. Fairbrother ,  John A. Flygare ,  Michael F. T. Koehler

IPC分类号： A61K31/517 ,  C07D239/72

CPC分类号： C07D239/94

摘要： The invention relates generally to small molecules that mimic the biological activity of certain peptides and proteins, to compositions containing them and to their use. In particular, the invention relates to compounds of the general formula (I) that mimic the biological activity of BH3-only proteins and are capable of binding to and neutralizing pro-survival Bcl-2 proteins: wherein A1, A2, B1, B2, B3, X, Z, R1, R2, R3 and t are as described herein. The invention also relates to processes of preparing the benzenesulfonamide compounds that mimic portions of peptides and proteins, and to the use of such compounds in the regulation of cell death and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death.

摘要翻译： 本发明一般涉及模拟某些肽和蛋白质的生物学活性的小分子，含有它们的组合物及其用途。 特别地，本发明涉及模拟仅含BH3蛋白的生物学活性的通式（I）的化合物，并能够结合并中和原生存Bcl-2蛋白：其中A1，A2，B1，B2， B3，X，Z，R1，R2，R3和t如本文所述。 本发明还涉及制备模仿肽和蛋白质的一部分的苯磺酰胺化合物的方法，以及这些化合物在调节细胞死亡中的用途以及治疗和/或预防与细胞死亡调节相关的疾病或病症 。

公开(公告)号：US08518970B2

公开(公告)日：2013-08-27

申请号：US13347364

申请日：2012-01-10

申请人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers ,  Peter Czabotar

发明人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers ,  Peter Czabotar

IPC分类号： C07D417/14 ,  A61K31/5377 ,  A61K31/538 ,  A61K31/496 ,  A61K31/498 ,  A61K31/4709

CPC分类号： C07D417/14 ,  C07D417/12 ,  C07D487/04

摘要： In one aspect, the present invention provides for a compound of Formula I in which in Formula I, the variables X1, X2a, X2b, X2c, R1, 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-xL proteins.

公开(公告)号：US20100210622A1

公开(公告)日：2010-08-19

申请号：US12641141

申请日：2009-12-17

申请人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Peter Czabotar ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A, Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Lisa A. Hasvold ,  Andrew M. Petros ,  Andrew J. Souers ,  Zhi-Fu Tao ,  Le Wang ,  Xilu Wang ,  Kurt Deshayes

发明人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Peter Czabotar ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A, Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Lisa A. Hasvold ,  Andrew M. Petros ,  Andrew J. Souers ,  Zhi-Fu Tao ,  Le Wang ,  Xilu Wang ,  Kurt Deshayes

IPC分类号： A61K31/4725 ,  C07D417/14 ,  A61P35/02 ,  A61P35/00 ,  A61P9/00 ,  A61P7/02 ,  C07D471/04 ,  A61K31/5377 ,  C07D487/04 ,  A61K31/519 ,  A61K31/496 ,  C07D471/06 ,  A61K31/4745

CPC分类号： C07D417/14 ,  C07D471/06 ,  C07D473/00 ,  C07D487/04 ,  C07D495/04 ,  C07D513/04 ,  C07D513/06

摘要： In one aspect, the present invention provides for a compound of Formula I in which the variable X1a, X1b, X1c, X1d, Q, A, R1, 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-xL proteins.

摘要翻译： 一方面，本发明提供了其中变量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的式I化合物 。 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：US08232273B2

公开(公告)日：2012-07-31

申请号：US12641141

申请日：2009-12-17

申请人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Peter Czabotar ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Lisa A. Hasvold ,  Andrew M. Petros ,  Andrew J. Souers ,  Zhi-Fu Tao ,  Le Wang ,  Xilu Wang ,  Kurt Deshayes

发明人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Peter Czabotar ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Lisa A. Hasvold ,  Andrew M. Petros ,  Andrew J. Souers ,  Zhi-Fu Tao ,  Le Wang ,  Xilu Wang ,  Kurt Deshayes

IPC分类号： A61K31/5377 ,  C07D413/14

CPC分类号： C07D417/14 ,  C07D471/06 ,  C07D473/00 ,  C07D487/04 ,  C07D495/04 ,  C07D513/04 ,  C07D513/06

摘要： In one aspect, the present invention provides for a compound of Formula I in which the variable X1a, X1b, X1c, X1d, Q, A, R1, 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-xL proteins.

摘要翻译： 一方面，本发明提供了其中变量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的式I化合物 。 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：US08114893B2

公开(公告)日：2012-02-14

申请号：US12641063

申请日：2009-12-17

申请人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers ,  Peter Czabotar

发明人： Jonathan Bayldon Baell ,  Chinh Thien Bui ,  Peter Colman ,  Danette A. Dudley ,  Wayne J. Fairbrother ,  John A. Flygare ,  Guillaume Laurent Lessene ,  Chudi Ndubaku ,  George Nikolakopoulos ,  Carl Steven Rye ,  Brad Edmund Sleebs ,  Brian John Smith ,  Keith Geoffrey Watson ,  Steven W. Elmore ,  Andrew M. Petros ,  Andrew J. Souers ,  Peter Czabotar

IPC分类号： C07D417/14 ,  A61K31/5377 ,  A61K31/538 ,  A61K31/496 ,  A61K31/498 ,  A61K31/4709

CPC分类号： C07D417/14 ,  C07D417/12 ,  C07D487/04

摘要： In one aspect, the present invention provides for a compound of Formula I in which in Formula I, the variables X1, X2a, X2b, X2c, R1, 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-xL proteins.

摘要翻译： 一方面，本发明提供式I化合物，其中在式I中，变量X1，X2a，X2b，X2c，R1，B，L，E，A和下标n如本文所定义。 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：US20100197711A1

公开(公告)日：2010-08-05

申请号：US12678836

申请日：2007-09-27

申请人： Keith Geoffrey Watson ,  Guillaume Laurent Lessene ,  Jonathan Bayldon Baell ,  David Ching Siang Huang ,  Ian Philip Street ,  Jerry McKee Adams ,  Peter Malcolm Colman ,  Brad Edmund Sleebs ,  Brian John Smith ,  Peter Edward Czabotar

发明人： Keith Geoffrey Watson ,  Guillaume Laurent Lessene ,  Jonathan Bayldon Baell ,  David Ching Siang Huang ,  Ian Philip Street ,  Jerry McKee Adams ,  Peter Malcolm Colman ,  Brad Edmund Sleebs ,  Brian John Smith ,  Peter Edward Czabotar

IPC分类号： A61K31/428 ,  C07D277/82 ,  C07D417/12 ,  C12N5/09 ,  A61K31/506 ,  A61K31/4439 ,  A61P29/00 ,  A61P35/00 ,  A61P37/00 ,  A61P35/02 ,  A61P19/02

CPC分类号： C07D417/12 ,  C07D277/82 ,  C07D417/14

摘要： The present invention relates to benzothiazole compounds that mimic the activity of BH3 only proteins and are capable of binding to and neutralizing pro survival Bcl 2 proteins. The invention also relates to the use of such compounds in the regulation of cell death or cell survival and the treatment and/or prophylaxis of diseases or conditions associated with the deregulation of cell death or cell survival.

摘要翻译： 本发明涉及苯并噻唑化合物，其类似于仅BH3蛋白的活性并且能够结合和中和生存的Bcl 2蛋白。 本发明还涉及这些化合物在调节细胞死亡或细胞存活以及治疗和/或预防与细胞死亡或细胞存活失调相关的疾病或病症中的用途。

公开(公告)号：US20110098305A1

公开(公告)日：2011-04-28

申请号：US12993574

申请日：2009-05-20

申请人： Jonathan Bayldon Baell ,  Guillaume Laurent Lessene ,  Brad Edmund Sleebs ,  Wayne Fairbrother ,  John Flygare ,  Michael F.T. Koehler

发明人： Jonathan Bayldon Baell ,  Guillaume Laurent Lessene ,  Brad Edmund Sleebs ,  Wayne Fairbrother ,  John Flygare ,  Michael F.T. Koehler

IPC分类号： A61K31/501 ,  C07D239/88 ,  A61K31/497 ,  C07D237/30 ,  A61P35/00

CPC分类号： C07D215/38

摘要： Disclosed are compounds which inhibit the activity of anti-apoptotic protein family members, compositions containing the compounds and uses of the compounds for preparing medicaments for treating diseases during which occurs expression one or more than one of an anti-apoptotic protein family member.

摘要翻译： 公开了抑制抗凋亡蛋白家族成员的活性的化合物，含有化合物的组合物和该化合物用于制备用于治疗疾病的药物的用途，其中发生表达一种或多种抗凋亡蛋白家族成员。