公开(公告)号：US10947315B2

公开(公告)日：2021-03-16

申请号：US16229028

申请日：2018-12-21

申请人： IMMUNOGEN, INC.

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

IPC分类号： C07D487/04 ,  C07D498/04 ,  C07D519/00 ,  A61K47/60 ,  A61P35/00 ,  C07K16/28 ,  A61K47/68 ,  A61K45/06 ,  A61K31/5517 ,  A61K38/07 ,  C07K5/103 ,  C07K5/02 ,  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：US20190263924A1

公开(公告)日：2019-08-29

申请号：US16205609

申请日：2018-11-30

申请人： IMMUNOGEN, INC.

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

IPC分类号： C07K16/30 ,  C07D519/00 ,  A61K45/06 ,  A61K31/5517 ,  A61K47/68 ,  C07D487/04 ,  A61P35/00 ,  A61K47/54

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：US20180037659A1

公开(公告)日：2018-02-08

申请号：US15677846

申请日：2017-08-15

申请人： IMMUNOGEN, INC.

发明人： Nathan Elliott Fishkin ,  Michael Louis Miller ,  Wei Li ,  Rajeeva Singh

IPC分类号： C07K16/30 ,  C07D487/04 ,  A61K47/68 ,  A61K47/54

CPC分类号： C07K16/30 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/545 ,  A61K47/6803 ,  A61K47/6849 ,  A61K47/6851 ,  A61K47/6867 ,  A61K2039/505 ,  A61P35/00 ,  C07D487/04 ,  C07D519/00 ,  C07K2317/24 ,  C07K2317/92 ,  C07K2317/94

摘要： The present invention is directed to methods of preparing a conjugate of a cell-binding agent and a drug (such as a cytotoxic compound). The methods comprise the use of an imine reactive compound to enable efficient conjugations of cytotoxic compounds with cell binding agents.

公开(公告)号：US20180002440A1

公开(公告)日：2018-01-04

申请号：US15645597

申请日：2017-07-10

申请人： IMMUNOGEN, INC.

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

IPC分类号： C07K16/30 ,  A61K47/54 ,  C07D519/00 ,  C07D487/04 ,  A61K31/5517 ,  A61K45/06 ,  A61K47/68 ,  A61K39/00

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：US09617270B2

公开(公告)日：2017-04-11

申请号：US14621813

申请日：2015-02-13

申请人： ImmunoGen, Inc.

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

IPC分类号： C07D487/04 ,  A61K47/48

CPC分类号： C07D487/04 ,  A61K47/60 ,  A61K47/6849

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：US20150166482A1

公开(公告)日：2015-06-18

申请号：US14539361

申请日：2014-11-12

申请人： ImmunoGen, Inc.

发明人： Wei Li ,  Robert Yongxin Zhao

IPC分类号： C07D213/71 ,  C07D401/12

CPC分类号： C07D401/12 ,  C07B2200/13 ,  C07D207/452 ,  C07D207/46 ,  C07D213/71

摘要： Processes for the preparation of charged crosslinkers bearing a sulfonic acid moiety are disclosed. These procedures also optionally include methods to convert the resulting products to substantially a single salt form.

摘要翻译： 公开了制备带有磺酸部分的带电交联剂的方法。 这些方法还任选地包括将所得产物转化为基本上单一盐形式的方法。

公开(公告)号：US20150030616A1

公开(公告)日：2015-01-29

申请号：US14316105

申请日：2014-06-26

申请人： ImmunoGen, Inc.

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

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

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：US11229639B2

公开(公告)日：2022-01-25

申请号：US17032219

申请日：2020-09-25

申请人： IMMUNOGEN, INC.

发明人： Ravi V. J. Chari ,  Wayne C. Widdison ,  Wei Li ,  David P. Pleynet

IPC分类号： A61K31/4745 ,  A61K47/68 ,  A61P35/00 ,  A61K39/395 ,  C07D491/22

摘要： Disclosed herein are novel cytotoxic compounds, and cytotoxic conjugates comprising these cytotoxic compounds and cell-binding agents. More specifically, this disclosure relates to novel camptothecin derivatives thereof, intermediates thereof, conjugates thereof, and pharmaceutically acceptable salts thereof, which are useful as medicaments, in particular as anti-proliferative agents (anticancer agents).

公开(公告)号：US20210238301A1

公开(公告)日：2021-08-05

申请号：US17143738

申请日：2021-01-07

申请人： IMMUNOGEN, INC.

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

IPC分类号： C07K16/28 ,  C07D498/04 ,  C07D519/00 ,  A61K47/60 ,  A61K47/68 ,  A61P35/00 ,  C07D487/04 ,  A61K45/06 ,  A61K31/5517 ,  A61K38/07 ,  C07K5/103 ,  C07K5/02 ,  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：US10208127B2

公开(公告)日：2019-02-19

申请号：US15974089

申请日：2018-05-08

申请人： ImmunoGen, Inc.

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 ,  C07K5/103 ,  A61K31/5517 ,  A61K45/06 ,  C07D519/00 ,  C07D498/04 ,  A61K47/68 ,  A61K47/60 ,  C07K19/00 ,  C07K16/46 ,  C07K5/02 ,  A61P35/00 ,  A61K38/07

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.