公开(公告)号：EP1909846B1

公开(公告)日：2018-12-26

申请号：EP06783938.1

申请日：2006-08-03

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick Henry ,  DE GROOT, Franciscus Marinus Hendrikus

IPC分类号： A61K47/68 ,  A61K47/65 ,  A61K47/56 ,  A61P35/00 ,  C07D249/04 ,  C07K5/083 ,  C07K5/065

CPC分类号： C07D249/04 ,  A61K47/56 ,  A61K47/65 ,  A61K47/6803 ,  C07K5/06078 ,  C07K5/0806

摘要： This invention relates to compounds comprising one or more therapeutic and/or diagnostic moieties and one or more functional moieties linked together via one or more triazole-containing linkers and to their intermediates and methods of their preparation. The triazole-containing linker may optionally contain one or more conditionally-cleavable or conditionally-transformable moieties and one or more spacer systems in between said moiety/moieties and the one or more therapeutic and/or diagnostic moieties.

公开(公告)号：EP3108886A2

公开(公告)日：2016-12-28

申请号：EP16176625.8

申请日：2011-04-21

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick Henry ,  COUMANS, Rudy Gerardus Elisabeth ,  ELGERSMA, Ronald Christiaan ,  MENGE, Wiro Michael Petrus Bernardus ,  JOOSTEN, Johannes Albertus Frederikus ,  SPIJKER, Henri Johannes ,  GROOT de, Franciscus Marinus Hendrikus

IPC分类号： A61K31/437 ,  A61P35/00 ,  A61K47/48 ,  C07D471/04

CPC分类号： A61K47/64 ,  A61K31/437 ,  A61K38/385 ,  A61K39/44 ,  A61K47/545 ,  A61K47/60 ,  A61K47/643 ,  A61K47/646 ,  A61K47/65 ,  A61K47/6803 ,  A61K47/6851 ,  C07D471/04

摘要： This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

摘要翻译： 本发明涉及DNA-烷化剂CC-1065及其缀合物的新型类似物。 此外，本发明涉及制备所述试剂和共轭物的中间体。 缀合物被设计成在一个或多个活化步骤之后和/或在由缀合物控制的速率和时间范围内释放它们的（多重）有效载荷，以选择性递送和/或可控地释放一种或多种所述DNA烷基化剂。 药剂，缀合物和中间体可用于治疗以不期望（细胞）增殖为特征的疾病。 作为实例，本发明的药剂和缀合物可用于治疗肿瘤。

公开(公告)号：EP3056203B1

公开(公告)日：2017-12-13

申请号：EP16154533.0

申请日：2011-04-21

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick Henry ,  COUMANS, Rudy Gerardus Elisabeth ,  ELGERSMA, Ronald Christiaan ,  MENGE, Wiro Michael Petrus Bernardus ,  JOOSTEN, Johannes Albertus Frederikus ,  SPIJKER, Henri Johannes ,  GROOT de, Franciscus Marinus Hendrikus

IPC分类号： A61K31/437 ,  C07D471/04 ,  A61K47/68 ,  A61P35/00

CPC分类号： A61K47/64 ,  A61K31/437 ,  A61K38/385 ,  A61K39/44 ,  A61K47/545 ,  A61K47/60 ,  A61K47/643 ,  A61K47/646 ,  A61K47/65 ,  A61K47/6803 ,  A61K47/6851 ,  C07D471/04

摘要： This invention relates to novel conjugates of the DNA-alkylating agent CC-1065. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The conjugates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the conjugates of this invention may be used to treat a tumor.

公开(公告)号：EP3108886A3

公开(公告)日：2017-03-22

申请号：EP16176625.8

申请日：2011-04-21

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick Henry ,  COUMANS, Rudy Gerardus Elisabeth ,  ELGERSMA, Ronald Christiaan ,  MENGE, Wiro Michael Petrus Bernardus ,  JOOSTEN, Johannes Albertus Frederikus ,  SPIJKER, Henri Johannes ,  GROOT de, Franciscus Marinus Hendrikus

IPC分类号： A61K31/437 ,  A61P35/00 ,  A61K47/48 ,  C07D471/04

CPC分类号： A61K47/64 ,  A61K31/437 ,  A61K38/385 ,  A61K39/44 ,  A61K47/545 ,  A61K47/60 ,  A61K47/643 ,  A61K47/646 ,  A61K47/65 ,  A61K47/6803 ,  A61K47/6851 ,  C07D471/04

摘要： This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

摘要翻译： 本发明涉及DNA-烷化剂CC-1065的新型缀合物。 缀合物被设计成在一个或多个活化步骤之后和/或在由缀合物控制的速率和时间范围内释放它们的（多重）有效载荷，以选择性递送和/或可控地释放一种或多种所述DNA烷基化剂。 缀合物可用于治疗以不期望（细胞）增殖为特征的疾病。 作为实例，本发明的缀合物可用于治疗肿瘤。

公开(公告)号：EP2560645A2

公开(公告)日：2013-02-27

申请号：EP11720340.6

申请日：2011-04-21

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick, Henry ,  COUMANS, Rudy, Gerardus, Elisabeth ,  ELGERSMA, Ronald, Christiaan ,  MENGE, Wiro, Michaël, Petrus, Bernardus ,  JOOSTEN, Johannes, Albertus, Frederikus ,  SPIJKER, Henri, Johannes ,  DE GROOT, Franciscus, Marinus, Hendrikus

IPC分类号： A61K31/437 ,  A61P35/00 ,  A61K47/48 ,  C07D471/04

CPC分类号： A61K47/64 ,  A61K31/437 ,  A61K38/385 ,  A61K39/44 ,  A61K47/545 ,  A61K47/60 ,  A61K47/643 ,  A61K47/646 ,  A61K47/65 ,  A61K47/6803 ,  A61K47/6851 ,  C07D471/04

摘要： This invention relates to novel conjugates of the DNA-alkylating agent CC-1065. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The conjugates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the conjugates of this invention may be used to treat a tumor.

摘要翻译： 本发明涉及DNA-烷化剂CC-1065的新型缀合物。 缀合物被设计成在一个或多个活化步骤之后和/或在由缀合物控制的速率和时间范围内释放它们的（多重）有效载荷，以选择性递送和/或可控地释放一种或多种所述DNA烷基化剂。 缀合物可用于治疗以不期望（细胞）增殖为特征的疾病。 作为实例，本发明的缀合物可用于治疗肿瘤。

公开(公告)号：EP1370298A1

公开(公告)日：2003-12-17

申请号：EP02727513.0

申请日：2002-03-25

申请人： Syntarga B.V.

发明人： DE GROOT, Franciscus, Marinus, Hendrikus ,  BEUSKER, Patrick, Henry ,  SCHEEREN, Johannes, Wilhelm ,  DE VOS, Dick ,  VAN BERKOM, Leonardus, Wilhelmus, Adriaan ,  BUSSCHER, Guuske, Frederike ,  SEELEN, Antoinette, Eugenie ,  KOEKKOEK, Ralph ,  ALBRECHT, Carsten

IPC分类号： A61K47/48

CPC分类号： B82Y5/00 ,  A61K47/65 ,  A61K47/67 ,  A61K47/6889 ,  A61K47/6899

摘要： This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V-(W)k-(X)1-A-Z, wherein: V is a specifier; (W)k-(X)1-A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclisation elimination spacer; Z is a therapeutic drug; k, 1 and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: - when A is (Y)m: k+1+m ≥ 1, and if k+1+m = 1; - when A is U: k+1 ≥ 1.

公开(公告)号：EP2173739B1

公开(公告)日：2013-07-31

申请号：EP07808517.2

申请日：2007-08-01

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick Henry ,  SPIJKER, Henri Johannes ,  JOOSTEN, Johannes Albertus Frederikus ,  HUIJBREGTS, Tijl ,  DE GROOT, Franciscus Marinus Hendrikus

IPC分类号： C07D403/06 ,  C07D403/14 ,  A61K31/403 ,  A61P35/00

CPC分类号： C07D403/06 ,  C07D403/14

公开(公告)号：EP2344478A2

公开(公告)日：2011-07-20

申请号：EP09748515.5

申请日：2009-11-03

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick Henry ,  COUMANS, Rudy Gerardus Elisabeth ,  ELGERSMA, Ronald Christiaan ,  MENGE, Wiro Michaël Petrus Bernardus ,  JOOSTEN, Johannes Albertus Frederikus ,  SPIJKER, Henri Johannes ,  DE GROOT, Franciscus Marinus Hendrikus

IPC分类号： C07D403/06

CPC分类号： C07D209/60 ,  A61K31/404 ,  A61K31/4184 ,  A61K31/423 ,  A61K31/428 ,  A61K31/4355 ,  A61K31/4365 ,  A61K31/437 ,  A61K47/6803 ,  C07D403/06 ,  C07D403/14 ,  C07D413/06 ,  C07D417/06 ,  C07D471/04 ,  C07D491/048 ,  C07D495/04

摘要： This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

摘要翻译： 本发明涉及DNA-烷化剂CC-1065及其缀合物的新型类似物。 此外，本发明涉及制备所述试剂和共轭物的中间体。 缀合物被设计成在一个或多个活化步骤之后和/或在由缀合物控制的速率和时间范围内释放它们的（多重）有效载荷，以选择性递送和/或可控地释放一种或多种所述DNA烷基化剂。 药剂，缀合物和中间体可用于治疗以不期望（细胞）增殖为特征的疾病。 作为实例，本发明的药剂和缀合物可用于治疗肿瘤。

公开(公告)号：EP1370298B1

公开(公告)日：2008-10-08

申请号：EP02727513.0

申请日：2002-03-25

申请人： Syntarga B.V.

发明人： DE GROOT, Franciscus, Marinus, Hendrikus ,  BEUSKER, Patrick, Henry ,  SCHEEREN, Johannes, Wilhelm ,  DE VOS, Dick ,  VAN BERKOM, Leonardus, Wilhelmus, Adriaan ,  BUSSCHER, Guuske, Frederike ,  SEELEN, Antoinette, Eugenie ,  KOEKKOEK, Ralph ,  ALBRECHT, Carsten

IPC分类号： A61K47/48

CPC分类号： B82Y5/00 ,  A61K47/65 ,  A61K47/67 ,  A61K47/6889 ,  A61K47/6899

摘要： This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V-(W)k-(X)1-A-Z, wherein: V is a specifier; (W)k-(X)1-A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclisation elimination spacer; Z is a therapeutic drug; k, 1 and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: - when A is (Y)m: k+1+m ≥ 1, and if k+1+m = 1; - when A is U: k+1 ≥ 1.

公开(公告)号：EP1909846A2

公开(公告)日：2008-04-16

申请号：EP06783938.1

申请日：2006-08-03

申请人： Syntarga B.V.

发明人： BEUSKER, Patrick Henry ,  DE GROOT, Franciscus Marinus Hendrikus

IPC分类号： A61K47/48

CPC分类号： C07D249/04 ,  A61K47/56 ,  A61K47/65 ,  A61K47/6803 ,  C07K5/06078 ,  C07K5/0806

摘要： This invention relates to compounds comprising one or more therapeutic and/or diagnostic moieties and one or more functional moieties linked together via one or more triazole-containing linkers and to their intermediates and methods of their preparation. The triazole-containing linker may optionally contain one or more conditionally-cleavable or conditionally-transformable moieties and one or more spacer systems in between said moiety/moieties and the one or more therapeutic and/or diagnostic moieties.

摘要翻译： 本发明涉及包含一个或多个治疗和/或诊断部分和通过一个或多个含三唑接头连接在一起的一个或多个功能部分的化合物及其中间体及其制备方法。 含有三唑的接头可以任选地在所述部分/部分之间和一个或多个治疗和/或诊断部分之间含有一个或多个可裂解或有条件可转化部分和一个或多个间隔体系。