公开(公告)号：US08809320B2

公开(公告)日：2014-08-19

申请号：US13774059

申请日：2013-02-22

申请人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

发明人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

IPC分类号： C07D519/00 ,  A61K31/5517 ,  A61P35/00 ,  A61K47/48 ,  C07D487/04 ,  A61K38/07 ,  A61K45/06 ,  C07D498/04 ,  C07K5/103 ,  C07K16/28

CPC分类号： C07K16/2896 ,  A61K31/5517 ,  A61K38/07 ,  A61K45/06 ,  A61K47/60 ,  A61K47/6835 ,  A61K47/6849 ,  A61K47/6863 ,  A61P35/00 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  C07K5/0202 ,  C07K5/1008 ,  C07K16/2803 ,  C07K16/46 ,  C07K19/00

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

摘要翻译： 本发明涉及具有抗增殖活性的新型苯并二氮杂衍生物，更具体地涉及式（I）和（II）的新型苯并二氮杂，其中二氮杂环（B）与杂环（CD）稠合，其中杂环是双环的 或其中二氮杂环（B）与杂环（C）稠合的式（III）化合物，其中杂环是单环的。 本发明提供这些化合物的细胞毒二聚体。 本发明还提供了单体和二聚体的共轭物。 本发明还提供了使用本发明的化合物或缀合物来抑制哺乳动物异常细胞生长或治疗增殖性病症的组合物和方法。 本发明还涉及将化合物或缀合物用于体外，原位和体内诊断或治疗哺乳动物细胞或相关病理状况的方法。

公开(公告)号：US08802667B2

公开(公告)日：2014-08-12

申请号：US13826181

申请日：2013-03-14

申请人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

发明人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V. J. Chari

IPC分类号： C07D519/00 ,  A61K31/5517 ,  A61K31/55 ,  A61P35/00 ,  A61K47/48 ,  C07K5/103 ,  C07D498/04 ,  A61K38/07 ,  A61K45/06 ,  C07D487/04 ,  C07K16/28

CPC分类号： C07K16/2896 ,  A61K31/5517 ,  A61K38/07 ,  A61K45/06 ,  A61K47/60 ,  A61K47/6835 ,  A61K47/6849 ,  A61K47/6863 ,  A61P35/00 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  C07K5/0202 ,  C07K5/1008 ,  C07K16/2803 ,  C07K16/46 ,  C07K19/00

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

公开(公告)号：US08889669B2

公开(公告)日：2014-11-18

申请号：US13827355

申请日：2013-03-14

申请人： Wei Li ,  Michael Louis Miller ,  Nathan Elliott Fishkin ,  Ravi V. J. Chari

发明人： Wei Li ,  Michael Louis Miller ,  Nathan Elliott Fishkin ,  Ravi V. J. Chari

IPC分类号： C07D519/00 ,  A61K31/5517 ,  A61K31/55 ,  A61K47/48 ,  C07D487/04 ,  A61K45/06

CPC分类号： C07K16/30 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/545 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6867 ,  A61K2039/505 ,  C07D487/04 ,  C07D519/00 ,  C07K2317/24 ,  C07K2317/92 ,  C07K2317/94

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

摘要翻译： 本发明涉及具有抗增殖活性的新型苯并二氮杂衍生物，更具体地涉及式（I） - （VII）的新型苯并二氮杂化合物。 本发明还提供了与细胞结合剂连接的苯并二氮杂类化合物的缀合物。 本发明还提供了使用本发明的化合物或缀合物来抑制哺乳动物异常细胞生长或治疗增殖性病症的组合物和方法。

公开(公告)号：US20130302359A1

公开(公告)日：2013-11-14

申请号：US13827355

申请日：2013-03-14

申请人： Wei Li ,  Michael Louis Miller ,  Nathan Elliott Fishkin ,  Ravi V.J. Chari

发明人： Wei Li ,  Michael Louis Miller ,  Nathan Elliott Fishkin ,  Ravi V.J. Chari

IPC分类号： A61K47/48 ,  A61K45/06

CPC分类号： C07K16/30 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/545 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6867 ,  A61K2039/505 ,  C07D487/04 ,  C07D519/00 ,  C07K2317/24 ,  C07K2317/92 ,  C07K2317/94

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

公开(公告)号：US20130302357A1

公开(公告)日：2013-11-14

申请号：US13826181

申请日：2013-03-14

申请人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V.J. Chari

发明人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V.J. Chari

IPC分类号： C07D487/04 ,  C07K16/28 ,  A61K45/06 ,  A61K38/07 ,  C07K5/103 ,  A61K47/48 ,  A61K31/5517

CPC分类号： C07K16/2896 ,  A61K31/5517 ,  A61K38/07 ,  A61K45/06 ,  A61K47/60 ,  A61K47/6835 ,  A61K47/6849 ,  A61K47/6863 ,  A61P35/00 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  C07K5/0202 ,  C07K5/1008 ,  C07K16/2803 ,  C07K16/46 ,  C07K19/00

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

公开(公告)号：US20130266596A1

公开(公告)日：2013-10-10

申请号：US13774059

申请日：2013-02-22

申请人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V.J. Chari

发明人： Wei Li ,  Nathan Elliott Fishkin ,  Robert Yongxin Zhao ,  Michael Louis Miller ,  Ravi V.J. Chari

IPC分类号： A61K47/48 ,  A61K45/06

CPC分类号： C07K16/2896 ,  A61K31/5517 ,  A61K38/07 ,  A61K45/06 ,  A61K47/60 ,  A61K47/6835 ,  A61K47/6849 ,  A61K47/6863 ,  A61P35/00 ,  C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  C07K5/0202 ,  C07K5/1008 ,  C07K16/2803 ,  C07K16/46 ,  C07K19/00

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepines of formula (I) and (II), in which the diazepine ring (B) is fused with a heterocyclic ring (CD), wherein the heterocyclic ring is bicyclic or a compound of formula (III), in which the diazepine ring (B) is fused with a heterocyclic ring (C), wherein the heterocyclic ring is monocyclic. The invention provides cytotoxic dimers of these compounds. The invention also provides conjugates of the monomers and the dimers. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention. The invention further relates to methods of using the compounds or conjugates for in vitro, in situ, and in vivo diagnosis or treatment of mammalian cells, or associated pathological conditions.

公开(公告)号：US08765740B2

公开(公告)日：2014-07-01

申请号：US13397195

申请日：2012-02-15

申请人： Wei Li ,  Michael Miller ,  Nathan Fishkin ,  Ravi V. J. Chari

发明人： Wei Li ,  Michael Miller ,  Nathan Fishkin ,  Ravi V. J. Chari

IPC分类号： C07D519/00 ,  A61K31/5517 ,  A61K31/55 ,  A61P35/00

CPC分类号： C07K16/30 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/545 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6867 ,  A61K2039/505 ,  C07D487/04 ,  C07D519/00 ,  C07K2317/24 ,  C07K2317/92 ,  C07K2317/94

摘要： The invention relates to novel benzodiazepine derivatives with antiproliferative activity and more specifically to novel benzodiazepine compounds of formula (I)-(VII). The invention also provides conjugates of the benzodiazepine compounds linked to a cell-binding agent. The invention further provides compositions and methods useful for inhibiting abnormal cell growth or treating a proliferative disorder in a mammal using the compounds or conjugates of the invention.

公开(公告)号：US08163736B2

公开(公告)日：2012-04-24

申请号：US12174195

申请日：2008-07-16

申请人： Laurence Gauzy ,  Herve Bouchard ,  Ravi V. J. Chari ,  Alain Commercon ,  Robert Zhao ,  Yonghong Deng ,  Wei Li

发明人： Laurence Gauzy ,  Herve Bouchard ,  Ravi V. J. Chari ,  Alain Commercon ,  Robert Zhao ,  Yonghong Deng ,  Wei Li

IPC分类号： C07D519/00 ,  C07D487/00 ,  A61K31/5517

CPC分类号： C07D487/04

摘要： The present invention is related to new tomaymycin derivatives, their process of preparation and their therapeutic uses.

摘要翻译： 本发明涉及新的茅屋霉素衍生物，其制备方法及其治疗用途。

公开(公告)号：US08665887B2

公开(公告)日：2014-03-04

申请号：US13059934

申请日：2009-07-29

申请人： Shu Ge ,  Jinxia Sun ,  Meng You ,  Wei Li ,  Wei Li ,  Yutian Nie ,  Yue Li ,  Lihong Wei ,  Sitao Lin

发明人： Shu Ge ,  Jinxia Sun ,  Meng You ,  Wei Li ,  Wei Li ,  Yutian Nie ,  Yue Li ,  Lihong Wei ,  Sitao Lin

IPC分类号： H04L12/28

CPC分类号： H04L45/04 ,  H04L45/50 ,  H04L45/52 ,  H04L45/741

摘要： A number automatic routing method, an updating method, a withdrawing method, a router and a device is provided wherein the number automatic routing method includes: converting to-be-distributed number into number routing information to add to dynamic routing protocol; generating a dynamic routing protocol message according to the number routing information; transmitting the dynamic routing protocol message through an Internet Protocol (IP) network and distributing the number through the dynamic routing protocol message and the IP network. The method supports automatic routing of numbers such as E.164 and E.214 and SP through expanding current Multi-Protocol Border Gateway Protocol (MP-BGP) that optimizes network structure and improves efficiency.

摘要翻译： 提供了一种数字自动路由方法，更新方法，撤销方法，路由器和设备，其中号码自动路由方法包括：将分配的号码转换为号码路由信息以添加到动态路由协议; 根据号码路由信息生成动态路由协议消息; 通过互联网协议（IP）网络传输动态路由协议消息，并通过动态路由协议消息和IP网络分配号码。 该方法通过扩展当前的优化网络结构并提高效率的多协议边界网关协议（MP-BGP）来支持自动路由数字，如E.164和E.214和SP。

公开(公告)号：US20110286466A1

公开(公告)日：2011-11-24

申请号：US13059934

申请日：2009-07-29

申请人： Shu Ge ,  Jinxia Sun ,  Meng You ,  Wei Li ,  Wei Li ,  Yutian Nie ,  Yue Li ,  Lihong Wei ,  Sitao Lin

发明人： Shu Ge ,  Jinxia Sun ,  Meng You ,  Wei Li ,  Wei Li ,  Yutian Nie ,  Yue Li ,  Lihong Wei ,  Sitao Lin

IPC分类号： H04L12/56

CPC分类号： H04L45/04 ,  H04L45/50 ,  H04L45/52 ,  H04L45/741

摘要： A number automatic routing method, an updating method, a withdrawing method, a router and a device is provided wherein the number automatic routing method includes: converting to-be-distributed number into number routing information to add to dynamic routing protocol; generating a dynamic routing protocol message according to the number routing information; transmitting the dynamic routing protocol message through an Internet Protocol (IP) network and distributing the number through the dynamic routing protocol message and the IP network. The method supports automatic routing of numbers such as E.164 and E.214 and SP through expanding current Multi-Protocol Border Gateway Protocol (MP-BGP) that optimizes network structure and improves efficiency.

摘要翻译： 提供了一种数字自动路由方法，更新方法，撤销方法，路由器和设备，其中号码自动路由方法包括：将分配的号码转换为号码路由信息以添加到动态路由协议; 根据号码路由信息生成动态路由协议消息; 通过互联网协议（IP）网络传输动态路由协议消息，并通过动态路由协议消息和IP网络分配号码。 该方法通过扩展当前的优化网络结构并提高效率的多协议边界网关协议（MP-BGP）来支持自动路由数字，如E.164和E.214和SP。