公开(公告)号：US07476741B2

公开(公告)日：2009-01-13

申请号：US10514426

申请日：2003-05-16

申请人： Sui Xiong Cai ,  Songchun Jiang ,  Giorgio Attardo ,  Réal Denis ,  Richard Storer ,  Rabindra Rej

发明人： Sui Xiong Cai ,  Songchun Jiang ,  Giorgio Attardo ,  Réal Denis ,  Richard Storer ,  Rabindra Rej

IPC分类号： C07D405/00

CPC分类号： C07D311/04 ,  C07D311/74 ,  C07D311/76

摘要： The present invention is directed to substituted 4H-chromenes, 2H-chromenes, chromans and analogs thereof, represented by the general Formula (I) wherein R5, A, B, X, Y, Z and dotted lines are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

摘要翻译： 本发明涉及其中R5，A，B，X，Y，Z和虚线由本文定义的通式（I）表示的取代的4H-色烯，2H-色烯，色满及其类似物。 本发明还涉及具有式（I）的化合物是胱天蛋白酶的激活剂和凋亡诱导剂的发现。 因此，本发明的胱天蛋白酶和细胞凋亡诱导剂的激活剂可用于诱导异常细胞发生不受控制的生长和扩散的各种临床病症中的细胞死亡。

公开(公告)号：US20050176750A1

公开(公告)日：2005-08-11

申请号：US10514426

申请日：2003-05-16

申请人： Sui Cai ,  Songchun Jiang ,  Giorgio Attardo ,  Real Denis ,  Richard Storer ,  Rabindra Rej

发明人： Sui Cai ,  Songchun Jiang ,  Giorgio Attardo ,  Real Denis ,  Richard Storer ,  Rabindra Rej

IPC分类号： A61K31/353 ,  A61K31/407 ,  A61K31/4188 ,  A61K31/4741 ,  C07D311/04 ,  C07D311/74 ,  C07D311/76

CPC分类号： C07D311/04 ,  C07D311/74 ,  C07D311/76

摘要： The present invention is directed to substituted 4H-chromenes, 2H-chromenes, chromans and analogs thereof, represented by the general Formula (I) wherein R5, A, B, X, Y, Z and dotted lines are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

摘要翻译： 本发明涉及由通式（I）表示的取代的4H-色烯，2H-色烯，着色剂及其类似物，其中R 5，A，B，X，Y，Z和虚线 线条在本文中定义。 本发明还涉及具有式（I）的化合物是胱天蛋白酶的激活剂和凋亡诱导剂的发现。 因此，本发明的胱天蛋白酶和细胞凋亡诱导剂的激活剂可用于诱导异常细胞发生不受控制的生长和扩散的各种临床病症中的细胞死亡。

公开(公告)号：US07528164B2

公开(公告)日：2009-05-05

申请号：US10514427

申请日：2003-05-16

申请人： Sui Xiong Cai ,  Songchun Jiang ,  William E. Kemnitzer ,  Hong Zhang ,  Giorgio Attardo ,  Real Denis

发明人： Sui Xiong Cai ,  Songchun Jiang ,  William E. Kemnitzer ,  Hong Zhang ,  Giorgio Attardo ,  Real Denis

IPC分类号： A61K31/407

CPC分类号： C07D491/04

摘要： The present invention is directed to substituted 4H-chromenes and analogs thereof, represented by the Formula (I): wherein R1, R3-R5, A, D, Y and Z are defined herein. The present invention also relates to the discovery that compounds having Formula (I) are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

摘要翻译： 本发明涉及由式（I）表示的取代的4H-色烯及其类似物：其中R1，R3-R5，A，D，Y和Z如本文所定义。 本发明还涉及具有式（I）的化合物是胱天蛋白酶的激活剂和凋亡诱导剂的发现。 因此，本发明的胱天蛋白酶和细胞凋亡诱导剂的激活剂可用于诱导异常细胞发生不受控制的生长和扩散的各种临床病症中的细胞死亡。

公开(公告)号：US07235674B2

公开(公告)日：2007-06-26

申请号：US10989057

申请日：2004-11-16

申请人： Sui Xiong Cai ,  Hong Zhang ,  William E. Kemnitzer ,  Songchun Jiang ,  John Drewe ,  Richard Storer

发明人： Sui Xiong Cai ,  Hong Zhang ,  William E. Kemnitzer ,  Songchun Jiang ,  John Drewe ,  Richard Storer

IPC分类号： C07D311/02 ,  C07D311/00

CPC分类号： C07D335/06 ,  A61K31/35 ,  A61K31/385 ,  A61K31/47 ,  C07D215/54 ,  C07D221/10 ,  C07D311/16 ,  C07D311/58 ,  C07D409/04 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D495/04 ,  C07D513/04

摘要： The present invention is directed to substituted coumarins and quinolines and analogs thereof, represented by the general Formula I: wherein A, B, X, Y, and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

摘要翻译： 本发明涉及由通式I表示的取代香豆素和喹啉及其类似物：其中A，B，X，Y和Z如本文所定义。 本发明还涉及发现具有式I的化合物是胱天蛋白酶的活化剂和凋亡诱导剂。 因此，本发明的胱天蛋白酶和细胞凋亡诱导剂的激活剂可用于诱导异常细胞发生不受控制的生长和扩散的各种临床病症中的细胞死亡。

公开(公告)号：US07015328B2

公开(公告)日：2006-03-21

申请号：US10146136

申请日：2002-05-16

申请人： Sui Xiong Cai ,  Hong Zhang ,  William E. Kemnitzer ,  Songchun Jiang ,  John Drewe ,  Richard Storer

发明人： Sui Xiong Cai ,  Hong Zhang ,  William E. Kemnitzer ,  Songchun Jiang ,  John Drewe ,  Richard Storer

IPC分类号： C07D311/04 ,  C07D405/00 ,  C07D217/02 ,  A61K31/47

CPC分类号： C07D335/06 ,  A61K31/35 ,  A61K31/385 ,  A61K31/47 ,  C07D215/54 ,  C07D221/10 ,  C07D311/16 ,  C07D311/58 ,  C07D409/04 ,  C07D471/04 ,  C07D491/04 ,  C07D493/04 ,  C07D495/04 ,  C07D513/04

摘要： The present invention is directed to substituted coumarins and quinolines and analogs thereof, represented by the general Formula I: wherein A, B, X, Y, and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

公开(公告)号：US06900325B2

公开(公告)日：2005-05-31

申请号：US10146136

申请日：2002-05-16

申请人： Sui Xiong Cai ,  Hong Zhang ,  William E. Kemnitzer ,  Songchun Jiang ,  John Drewe ,  Richard Storer

发明人： Sui Xiong Cai ,  Hong Zhang ,  William E. Kemnitzer ,  Songchun Jiang ,  John Drewe ,  Richard Storer

摘要： The present invention is directed to substituted coumarins and quinolines and analogs thereof, represented by the general Formula I: wherein A, B, X, Y, and Z are defined herein. The present invention also relates to the discovery that compounds having Formula I are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

公开(公告)号：US07842805B2

公开(公告)日：2010-11-30

申请号：US11773293

申请日：2007-07-03

申请人： Sui Xiong Cai ,  Mark B. Anderson ,  Adam Willardsen ,  Songchun Jiang ,  Robert J. Halter ,  Rachel Slade ,  Yevgeniya Klimova

发明人： Sui Xiong Cai ,  Mark B. Anderson ,  Adam Willardsen ,  Songchun Jiang ,  Robert J. Halter ,  Rachel Slade ,  Yevgeniya Klimova

IPC分类号： C07D403/12 ,  C07D253/08 ,  A61K31/53 ,  A61P35/00

CPC分类号： C07D237/34 ,  C07D253/08

摘要： Disclosed are 1-arylamino-phthalazines, 4-arylamino-benzo[d][1,2,3]triazines, and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

摘要翻译： 公开了1-芳基氨基 - 酞嗪，4-芳基氨基 - 苯并[d] [1,2,3]三嗪及其类似物作为胱天蛋白酶的活化剂和凋亡诱导剂。 本发明的化合物可用于治疗异常细胞发生不受控制的生长和扩散的各种临床病症。

公开(公告)号：US07592143B2

公开(公告)日：2009-09-22

申请号：US10826909

申请日：2004-04-19

申请人： Shailaja Kasibhatla ,  Sui Xiong Cai ,  Ben Tseng ,  Katayoun Alavi Jessen ,  Nicole Marion English ,  Serguei Maliartchouk ,  Songchun Jiang ,  Nilantha Sudath Sirisoma ,  Han-Zhong Zhang ,  Jared Kuemmerle

发明人： Shailaja Kasibhatla ,  Sui Xiong Cai ,  Ben Tseng ,  Katayoun Alavi Jessen ,  Nicole Marion English ,  Serguei Maliartchouk ,  Songchun Jiang ,  Nilantha Sudath Sirisoma ,  Han-Zhong Zhang ,  Jared Kuemmerle

IPC分类号： G01N33/53

CPC分类号： A61K49/0052 ,  A61K31/352 ,  A61K49/0043 ,  A61K51/0412 ,  A61K51/0419 ,  A61K51/0421 ,  A61K51/0453 ,  A61K51/0495

摘要： The present invention relates to screening methods useful for drug discovery of apoptosis inducing compounds. In particular, the screening methodology relates to using Apoptosis Inducing Proteins (AIPs) as a target for the discovery of apoptosis activators useful as anticancer agents. The screening methods of the present invention can employ homogenous or heterogeneous binding assays using purified or partially purified AIPs; or whole cell assays using cells with altered levels of one or more AIPs. The invention also contemplates use of gambogic acid or GA-related compounds which bind AIPs and can accordingly be used to raise antibodies useful for drug discovery. Alternatively, labeled GA is used for competitive binding assays for drug discovery. Such assays afford high throughput screening of chemical libraries for apoptosis activators.

摘要翻译： 本发明涉及可用于药物发现凋亡诱导化合物的筛选方法。 特别地，筛选方法涉及使用细胞凋亡诱导蛋白（AIPs）作为发现用作抗癌剂的凋亡激活剂的靶标。 本发明的筛选方法可以使用纯化或部分纯化的AIPs进行均一或异质结合测定; 或使用具有改变水平的一种或多种AIP的细胞的全细胞测定。 本发明还考虑使用结合AIP的葡萄糖酸或GA相关化合物，因此可以用于产生可用于药物发现的抗体。 或者，标记的GA用于药物发现的竞争性结合测定。 这样的测定提供用于凋亡激活剂的化学文库的高通量筛选。

公开(公告)号：US20080032974A1

公开(公告)日：2008-02-07

申请号：US11779086

申请日：2007-07-17

申请人： Sui Xiong Cai ,  Nilantha Sirisoma ,  Azra Pervin ,  John Drewe ,  Shailaja Kasibhatla ,  Songchun Jiang ,  Hong Zhang ,  Chris Pleiman ,  Vijay Baichwal ,  John Manfredi ,  Leena Bhoite

发明人： Sui Xiong Cai ,  Nilantha Sirisoma ,  Azra Pervin ,  John Drewe ,  Shailaja Kasibhatla ,  Songchun Jiang ,  Hong Zhang ,  Chris Pleiman ,  Vijay Baichwal ,  John Manfredi ,  Leena Bhoite

IPC分类号： A61K31/517 ,  A61K31/52 ,  A61K31/5377 ,  A61P31/10 ,  A61P35/00 ,  C07D239/94 ,  C07D401/12 ,  C07D413/12 ,  C07D473/16

CPC分类号： C07D239/94 ,  C07D239/95 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D405/12 ,  C07D471/04 ,  C07D473/34 ,  C07D487/04

摘要： Disclosed are 4-arylamino-quinazolines and analogs thereof effective as activators of caspases and inducers of apoptosis. The compounds of this invention are useful in the treatment of a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

公开(公告)号：US07622497B2

公开(公告)日：2009-11-24

申请号：US10580263

申请日：2004-12-17

申请人： Sui Xiong Cai ,  Songchun Jiang ,  Han-Zhong Zhang

发明人： Sui Xiong Cai ,  Songchun Jiang ,  Han-Zhong Zhang

IPC分类号： A61K31/5377 ,  A61K31/496 ,  A61K31/352 ,  C07D265/30 ,  C07D493/22 ,  C07D241/04

CPC分类号： C07D493/22 ,  A61K31/352 ,  A61K31/366 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/655

摘要： The present invention is directed to novel derivatives of gambogic acid and analogs thereof. The present invention also relates to the discovery that novel derivatives of gambogic acid are activators of caspases and inducers of apoptosis. Therefore, the activators of caspases and inducers of apoptosis of this invention can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs.

摘要翻译： 本发明涉及吡啶酸及其类似物的新型衍生物。 本发明还涉及这样的发现：葡聚糖酸的新衍生物是胱天蛋白酶的活化剂和凋亡诱导剂。 因此，本发明的胱天蛋白酶和细胞凋亡诱导剂的激活剂可用于诱导异常细胞发生不受控制的生长和扩散的各种临床病症中的细胞死亡。