公开(公告)号：US07968595B2

公开(公告)日：2011-06-28

申请号：US11822535

申请日：2007-07-06

申请人： Sui Xiong Cai ,  John A. Drewe ,  Shailaja Kasibhatla ,  William D. Kemnitzer ,  Ben Y. Tseng ,  Charles Blais ,  Denis Labrecque ,  Henriette Gourdeau

发明人： Sui Xiong Cai ,  John A. Drewe ,  Shailaja Kasibhatla ,  William D. Kemnitzer ,  Ben Y. Tseng ,  Charles Blais ,  Denis Labrecque ,  Henriette Gourdeau

IPC分类号： A61K31/353 ,  C07D311/58

CPC分类号： C07D405/12 ,  C07D311/58

摘要： The present invention is directed to a substituted 4H-chromene represented by the Formula 1R, substantially free from the corresponding (S)-stereoisomer: The present invention also relates to the discovery that compound 1R, substantially free from the corresponding (S)-stereoisomer, is an activator of caspases and inducer of apoptosis, as well as an antivascular agent. Therefore, compound 1R, substantially free from the corresponding (S)-stereoisomer, can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs. Compound 1R, substantially free from the corresponding (S)-stereoisomer, also can be used for the treatment of diseases due to overgrowth of vasculature, such as solid tumors and ocular neovascularization.

摘要翻译： 本发明涉及基本上不含相应（S） - 立体异构体的由式1R表示的取代的4H-色烯。本发明还涉及发现基本上不含相应的（S） - 立体异构体的化合物1R 是胱天蛋白酶和凋亡诱导剂的激活剂，以及抗血管性药剂。 因此，基本上不含相应（S） - 立体异构体的化合物1R可用于诱发异常细胞发生不受控制的生长和扩散的各种临床条件下的细胞死亡。 基本上不含相应（S） - 立体异构体的化合物1R也可用于治疗由于脉管系统过度生长（如实体瘤和眼新生血管形成）引起的疾病。

公开(公告)号：US20080085328A1

公开(公告)日：2008-04-10

申请号：US11822535

申请日：2007-07-06

申请人： Sui Xiong Cai ,  John A. Drewe ,  Shailaja Kasibhatla ,  William E. Kemnitzer ,  Ben Y. Tseng ,  Charles Blais ,  Denis Labrecque ,  Henriette Gourdeau

发明人： Sui Xiong Cai ,  John A. Drewe ,  Shailaja Kasibhatla ,  William E. Kemnitzer ,  Ben Y. Tseng ,  Charles Blais ,  Denis Labrecque ,  Henriette Gourdeau

IPC分类号： A61K31/352 ,  A61K31/351 ,  A61K31/403 ,  A61K31/4035 ,  A61K31/436 ,  A61K31/4412 ,  A61K31/502 ,  A61K31/513 ,  A61K31/661 ,  A61K33/24 ,  A61P17/00 ,  A61P35/00 ,  A61P35/02 ,  A61P37/00 ,  C07D311/68

CPC分类号： C07D405/12 ,  C07D311/58

摘要： The present invention is directed to a substituted 4H-chromene represented by the Formula 1R, substantially free from the corresponding (S)-stereoisomer: The present invention also relates to the discovery that compound 1R, substantially free from the corresponding (S)-stereoisomer, is an activator of caspases and inducer of apoptosis, as well as an antivascular agent. Therefore, compound 1R, substantially free from the corresponding (S)-stereoisomer, can be used to induce cell death in a variety of clinical conditions in which uncontrolled growth and spread of abnormal cells occurs. Compound 1R, substantially free from the corresponding (S)-stereoisomer, also can be used for the treatment of diseases due to overgrowth of vasculature, such as solid tumors and ocular neovascularization.

摘要翻译： 本发明涉及基本上不含相应（S） - 立体异构体的由式1R表示的取代的4H-色烯。本发明还涉及发现基本上不含相应的（S） - 立体异构体的化合物1R 是胱天蛋白酶和凋亡诱导剂的激活剂，以及抗血管性药剂。 因此，基本上不含相应（S） - 立体异构体的化合物1R可用于诱发异常细胞发生不受控制的生长和扩散的各种临床条件下的细胞死亡。 基本上不含相应（S） - 立体异构体的化合物1R也可用于治疗由于脉管系统过度生长（如实体瘤和眼新生血管形成）引起的疾病。

公开(公告)号：US07135480B2

公开(公告)日：2006-11-14

申请号：US10733229

申请日：2003-12-12

申请人： Sui Xiong Cai ,  John A Drewe ,  Sungchun Jiang ,  Shailaja Kasibhatla ,  Jared Daniel Kuemmerle ,  Nilantha Sudath Sirisoma ,  Han-Zhong Zhang

发明人： Sui Xiong Cai ,  John A Drewe ,  Sungchun Jiang ,  Shailaja Kasibhatla ,  Jared Daniel Kuemmerle ,  Nilantha Sudath Sirisoma ,  Han-Zhong Zhang

IPC分类号： A61K31/4745 ,  C07D471/02

CPC分类号： C07D471/04 ,  A61K31/4745 ,  A61K31/496 ,  A61K31/4985 ,  C07D471/14 ,  C07D487/04

摘要： The present invention is directed to substituted 1-benzoyl-3-cyano-pyrrolo[1,2-α]quinolines and analogs thereof, represented by the general Formula I: wherein R1–R8, L, Q, dash line and Ar 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1-苯甲酰基-3-氰基 - 吡咯并[1,2-a]喹啉及其类似物：其中R 1〜 8，L，Q，虚线和Ar在本文中定义。 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：US07041685B2

公开(公告)日：2006-05-09

申请号：US10164705

申请日：2002-06-10

申请人： Sui Xiong Cai ,  Han-Zhong Zhang ,  John A. Drewe ,  P. Sanjeeva Reddy ,  Shailaja Kasibhatla ,  Jared Daniel Kuemmerle ,  Kristin P. Ollis

发明人： Sui Xiong Cai ,  Han-Zhong Zhang ,  John A. Drewe ,  P. Sanjeeva Reddy ,  Shailaja Kasibhatla ,  Jared Daniel Kuemmerle ,  Kristin P. Ollis

IPC分类号： A61K31/44 ,  C07D413/14

CPC分类号： C07D413/14 ,  A61K31/335 ,  A61K31/38 ,  A61K31/395 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/14 ,  C07D471/04

摘要： The present invention is directed to substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: wherein Ar1, Ar3, A, B and D 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 may 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3-芳基-5-芳基 - [1,2,4] - 恶二唑及其类似物：其中Ar 1，Ar 3 A，B和D在本文中定义。 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在异常细胞发生不受控制的生长和扩散的各种临床病症中诱导细胞死亡。

公开(公告)号：US07256219B2

公开(公告)日：2007-08-14

申请号：US10471720

申请日：2002-03-14

申请人： Sui Xiong Cai ,  P. Sanjeeva Reddy ,  John A. Drewe ,  Bao Ngoc Nguyen ,  Shailaja Kasibhatla

发明人： Sui Xiong Cai ,  P. Sanjeeva Reddy ,  John A. Drewe ,  Bao Ngoc Nguyen ,  Shailaja Kasibhatla

IPC分类号： A61K31/12 ,  C07C49/00 ,  C07D333/00 ,  C07D307/02 ,  C07D221/02 ,  C07D209/04 ,  C07D207/18

CPC分类号： C07D213/50 ,  A61K31/12 ,  A61K31/34 ,  A61K31/40 ,  A61K31/47 ,  A61K45/06 ,  C07C45/74 ,  C07C49/84 ,  C07C205/45 ,  A61K2300/00

摘要： The present invention is directed to multifluoro-substituted Chalcones and analogs thereof, represented by the general Formula I: wherein Ar and R6-R10 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 may 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表示的多氟取代的查尔酮及其类似物：其中Ar和R 6 -R 10是本文定义的。 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在异常细胞发生不受控制的生长和扩散的各种临床病症中诱导细胞死亡。

公开(公告)号：US07176234B2

公开(公告)日：2007-02-13

申请号：US10609670

申请日：2003-07-01

申请人： Sui Xiong Cai ,  Shailaja Kasibhatla ,  Kristin P. Ollis ,  Han-Zhong Zhang ,  John A. Drewe ,  Ben Tseng ,  Nilantha Sudath Sirisoma

发明人： Sui Xiong Cai ,  Shailaja Kasibhatla ,  Kristin P. Ollis ,  Han-Zhong Zhang ,  John A. Drewe ,  Ben Tseng ,  Nilantha Sudath Sirisoma

IPC分类号： A61K31/352 ,  C07D313/06

CPC分类号： A61K31/00 ,  C07D493/20

摘要： The present invention is directed to derivatives of gambogic acid and analogs thereof. Exemplary gambogic acid derivatives of the present invention include, among others, derivatives substituted in the C10 and C28 positions of gambogic acid. The present invention also relates to the discovery that certain preferred compounds of the present invention 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衍生物。 本发明的示例性的吡咯烷酸衍生物包括其中取代为吡咯烷酸的C10和C28位置的衍生物。 本发明还涉及本发明的某些优选化合物是胱天蛋白酶的活化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：US06462041B1

公开(公告)日：2002-10-08

申请号：US09495120

申请日：2000-02-01

申请人： Sui Xiong Cai ,  Han-Zhong Zhang ,  Yan Wang ,  Ben Tseng ,  Shailaja Kasibhatla ,  John A. Drewe

发明人： Sui Xiong Cai ,  Han-Zhong Zhang ,  Yan Wang ,  Ben Tseng ,  Shailaja Kasibhatla ,  John A. Drewe

IPC分类号： A61K3145

CPC分类号： C07D493/20 ,  A61K31/352 ,  A61K31/4025 ,  A61K31/4178 ,  A61K31/4188 ,  A61K31/4433 ,  A61K31/45 ,  A61K31/453 ,  A61K31/496 ,  A61K31/497 ,  A61K31/5377 ,  A61K31/5513 ,  C07D493/22 ,  C07D519/00

摘要： The present invention is directed to gambogic acid, analogs and derivatives thereof, represented by the general Formulae I-III: wherein R1-R5 are defined herein. The present invention also relates to the discovery that compounds having Formula I-III 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 cell growth and spread of abnormal cells occurs.

摘要翻译： 本发明涉及由通式I-III表示的吡咯烷酸，类似物及其衍生物：其中R1-R5在本文中定义。 本发明还涉及发现具有式I-III的化合物是胱天蛋白酶的激活剂和凋亡诱导剂。 因此，本发明的胱天蛋白酶和细胞凋亡诱导剂的激活剂可以用于在发生不受控制的细胞生长和异常细胞扩散的各种临床条件下诱导细胞死亡。

公开(公告)号：US07435750B2

公开(公告)日：2008-10-14

申请号：US11074077

申请日：2005-03-08

申请人： Sui Xiong Cai ,  Han-Zhong Zhang ,  John A. Drewe ,  P. Sanjeeva Reddy ,  Shailaja Kasibhatla ,  Jared Daniel Kuemmerle ,  Kristin P. Ollis

发明人： Sui Xiong Cai ,  Han-Zhong Zhang ,  John A. Drewe ,  P. Sanjeeva Reddy ,  Shailaja Kasibhatla ,  Jared Daniel Kuemmerle ,  Kristin P. Ollis

IPC分类号： A61K31/422 ,  A61K31/4245 ,  A61K31/443 ,  A61K31/4709 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4025 ,  A61K31/381 ,  A61K31/341 ,  A61K31/519 ,  A61K31/4725

CPC分类号： C07D413/14 ,  A61K31/335 ,  A61K31/38 ,  A61K31/395 ,  C07D409/04 ,  C07D409/14 ,  C07D413/04 ,  C07D417/14 ,  C07D471/04

摘要： The present invention is directed to substituted 3-aryl-5-aryl-[1,2,4]-oxadiazoles and analogs thereof, represented by the Formula I: wherein Ar1, Ar3, A, B and D 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 may 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3-芳基-5-芳基 - [1,2,4] - 恶二唑及其类似物：其中Ar 1，Ar 3 A，B和D在本文中定义。 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在异常细胞发生不受控制的生长和扩散的各种临床病症中诱导细胞死亡。

公开(公告)号：US07618975B2

公开(公告)日：2009-11-17

申请号：US10885903

申请日：2004-07-06

申请人： Sui Xiong Cai ,  Nilantha Sudath Sirisoma ,  Azra Pervin ,  John A. Drewe ,  Shailaja Kasibhatla ,  Songchun Jiang ,  Hong Zhang ,  Chris Pleiman

发明人： Sui Xiong Cai ,  Nilantha Sudath Sirisoma ,  Azra Pervin ,  John A. Drewe ,  Shailaja Kasibhatla ,  Songchun Jiang ,  Hong Zhang ,  Chris Pleiman

IPC分类号： A01N43/90 ,  A01N43/54 ,  A61K31/519 ,  A61K31/517 ,  C07D413/00 ,  C07D473/00 ,  C07D401/00 ,  C07D403/00 ,  C07D417/00 ,  C07D419/00 ,  C07D239/72

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.

摘要翻译： 公开了作为胱天蛋白酶的活化剂和凋亡诱导剂的4-芳基氨基 - 喹唑啉及其类似物。 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：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.