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：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：US20080153802A1

公开(公告)日：2008-06-26

申请号：US11642591

申请日：2006-12-21

申请人： Guillaume Laurent Lessene ,  Jonathan Baell

发明人： Guillaume Laurent Lessene ,  Jonathan Baell

IPC分类号： C07C275/54 ,  A61K31/197 ,  A61K31/381 ,  A61K31/404 ,  C07D209/18 ,  C07D265/30 ,  C07D487/00 ,  C07D333/50 ,  C07D213/46 ,  A61K31/44 ,  A61K31/5375 ,  A61K31/55

CPC分类号： C07C275/54 ,  C07C323/44 ,  C07C323/59 ,  C07C323/60 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/14 ,  C07D209/26 ,  C07D213/40 ,  C07D213/56 ,  C07D223/16 ,  C07D333/60

摘要： Benzoyl urea derivatives that are alpha helical peptides mimetics that mimic BH3-only proteins, compositions containing them, their conjugation to cell-targeting-moieties, and their use in the regulation of cell death are disclosed. The benzoyl urea derivatives are capable of binding to and neutralizing pro-survival Bcl-2 proteins. Use of benzoyl urea derivatives in the treatment and/or prophylaxis of diseases or conditions associated with deregulation of cell death are also described.

摘要翻译： 公开了作为模拟仅含BH3蛋白质的α螺旋肽模拟物，含有它们的组合物，其与细胞靶向部分的缀合及其在调节细胞死亡中的用途的苯甲酰脲衍生物。 苯甲酰脲衍生物能够结合并中和原始存活的Bcl-2蛋白。 还描述了苯甲酰脲衍生物在治疗和/或预防与细胞死亡调节相关的疾病或病症中的用途。

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：US20130184274A1

公开(公告)日：2013-07-18

申请号：US13809369

申请日：2011-07-08

申请人： Guillaume Laurent Lessene ,  Jonathan Bayldon Baell ,  Antony Wilks Burgess ,  Hiroshi Maruta

发明人： Guillaume Laurent Lessene ,  Jonathan Bayldon Baell ,  Antony Wilks Burgess ,  Hiroshi Maruta

IPC分类号： C07D487/04

CPC分类号： C07D487/04 ,  A61K31/519

摘要： The present invention relates to chemical compounds of formula (I) and methods for their use and preparation. In particular, the invention relates to substituted pyrazolo[3,4-d]pyrimidine based compounds which can be used in treating proliferative disorders, use of these compounds in methods of therapy and the manufacture of medicaments as well as compositions containing these compounds.

摘要翻译： 本发明涉及式（I）的化合物及其使用和制备方法。 特别地，本发明涉及可用于治疗增殖性疾病的取代的吡唑并[3,4-d]嘧啶基化合物，在治疗方法和制备药物中使用这些化合物以及含有这些化合物的组合物。

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：US08962830B2

公开(公告)日：2015-02-24

申请号：US13809369

申请日：2011-07-08

申请人： Guillaume Laurent Lessene ,  Jonathan Bayldon Baell ,  Antony Wilks Burgess ,  Hiroshi Maruta

发明人： Guillaume Laurent Lessene ,  Jonathan Bayldon Baell ,  Antony Wilks Burgess ,  Hiroshi Maruta

IPC分类号： C07D487/00 ,  A61K31/519 ,  C07D487/04

CPC分类号： C07D487/04 ,  A61K31/519

摘要： The present invention relates to chemical compounds of formula (I) and methods for their use and preparation. In particular, the invention relates to substituted pyrazolo[3,4-d]pyrimidine based compounds which can be used in treating proliferative disorders, use of these compounds in methods of therapy and the manufacture of medicaments as well as compositions containing these compounds.

摘要翻译： 本发明涉及式（I）的化合物及其使用和制备方法。 特别地，本发明涉及可用于治疗增殖性疾病的取代的吡唑并[3,4-d]嘧啶基化合物，在治疗方法和制备药物中使用这些化合物以及含有这些化合物的组合物。

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：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 。