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1. 发明申请

US20100113425A1 PYRROLOBENZODIAZEPINES 有权
标题翻译： PYRROBOBENZODIAZEPINES
公开(公告)号：US20100113425A1
公开(公告)日：2010-05-06
申请号：US12610478
申请日：2009-11-02
申请人： Philip Wilson Howard , Zhizhi Chen , Stephen John Gregson
发明人： Philip Wilson Howard , Zhizhi Chen , Stephen John Gregson
IPC分类号： A61K31/551 , A61P35/02 , A61P35/00 , C07D487/04
CPC分类号： C07D519/00
摘要： Compounds of the formula I: or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo; where R and R′ are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR′, nitro, Me3Sn and halo; R″ is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2′, R6′, R7′, R9′, X′ and M′ are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M′ may together represent a divalent pharmaceutically acceptable cation.
摘要翻译：式I化合物或其溶剂化物，其中：R2是任选取代的C5-20芳基; R 6和R 9独立地选自H，R，OH，OR，SH，SR，NH 2，NHR，NRR'，硝基，Me 3 Sn和卤素; 其中R和R'独立地选自任选取代的C 1-12烷基，C 3-20杂环基和C 5-20芳基; R 7选自H，R，OH，OR，SH，SR，NH 2，NHR，NHRR'，硝基，Me 3 Sn和卤素; R“是C3-12亚烷基，该链可被一个或多个杂原子和/或芳环中断; X选自O，S或NH; z是2或3; M是一价药学上可接受的阳离子; R 2'，R 6'，R 7'，R 9'，X'和M'分别选自与R 2，R 6，R 7，R 9，X和M相同的基团，或M和M'可以一起表示二价药学上可接受的阳离子。

2. 发明授权

US08633185B2 Pyrrolobenzodiazepines 有权
标题翻译：吡咯并苯并二氮杂卓
公开(公告)号：US08633185B2
公开(公告)日：2014-01-21
申请号：US12610478
申请日：2009-11-02
申请人： Philip Wilson Howard , Zhizhi Chen , Stephen John Gregson
发明人： Philip Wilson Howard , Zhizhi Chen , Stephen John Gregson
IPC分类号： C07D519/00 , A61K31/5517 , A61P35/00
CPC分类号： C07D519/00
摘要： Compounds of the formula I: or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo; where R and R′ are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR′, nitro, Me3Sn and halo; R″ is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2′, R6′, R7′, R9′, X′ and M′ are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M′ may together represent a divalent pharmaceutically acceptable cation.
摘要翻译：式I化合物或其溶剂化物，其中：R2是任选取代的C5-20芳基; R 6和R 9独立地选自H，R，OH，OR，SH，SR，NH 2，NHR，NRR'，硝基，Me 3 Sn和卤素; 其中R和R'独立地选自任选取代的C 1-12烷基，C 3-20杂环基和C 5-20芳基; R 7选自H，R，OH，OR，SH，SR，NH 2，NHR，NHRR'，硝基，Me 3 Sn和卤素; R“是C3-12亚烷基，该链可被一个或多个杂原子和/或芳环中断; X选自O，S或NH; z为2或3; M是一价药学上可接受的阳离子; R 2'，R 6'，R 7'，R 9'，X'和M'分别选自与R 2，R 6，R 7，R 9，X和M相同的基团，或M和M'可以一起表示二价药学上可接受的阳离子。

3. 发明授权

US08501934B2 Pyrrolobenzodiazepines 有权
标题翻译：吡咯并苯并二氮杂卓
公开(公告)号：US08501934B2
公开(公告)日：2013-08-06
申请号：US13055194
申请日：2009-07-22
申请人： Philip Wilson Howard , Stephen John Gregson , Zhizhi Chen , Arnaud Charles Tiberghien , Luke Masterson
发明人： Philip Wilson Howard , Stephen John Gregson , Zhizhi Chen , Arnaud Charles Tiberghien , Luke Masterson
IPC分类号： A61P35/00 , A61K31/5517 , C07D487/04
CPC分类号： C07D487/04
摘要： Methods of preparing ZC-423 (I) which result in varying enantiomeric ratios.
摘要翻译：制备ZC-423（I）的方法，其导致不同的对映异构体比例。

4. 发明申请

US20110162227A1 PYRROLOBENZODIAZEPINES 有权
标题翻译： PYRROBOBENZODIAZEPINES
公开(公告)号：US20110162227A1
公开(公告)日：2011-07-07
申请号：US13055194
申请日：2009-07-22
申请人： Philip Wilson Howard , Stephen John Gregson , Zhizhi Chen , Arnaud Charles Tiberghien , Luke Masterson
发明人： Philip Wilson Howard , Stephen John Gregson , Zhizhi Chen , Arnaud Charles Tiberghien , Luke Masterson
IPC分类号： C07D487/04 , F26B5/06
CPC分类号： C07D487/04
摘要： Methods of preparing ZC-423 (I) which result in varying enantiomeric ratios.
摘要翻译：制备ZC-423（I）的方法，其导致不同的对映异构体比例。

5. 发明申请

US20110201803A1 PYRROLOBENZODIAZEPINES 有权
标题翻译： PYRROBOBENZODIAZEPINES
公开(公告)号：US20110201803A1
公开(公告)日：2011-08-18
申请号：US13124232
申请日：2009-10-16
申请人： Philip Wilson Howard , Stephen John Gregson , Zhizhi Chen , Arnaud Charles Tiberghien , Luke Masterson
发明人： Philip Wilson Howard , Stephen John Gregson , Zhizhi Chen , Arnaud Charles Tiberghien , Luke Masterson
IPC分类号： C07D487/04
CPC分类号： C07D519/00
摘要： The invention relates to certain pyrrolobenzodiazepines (PBDs), and in particular pyrrolobenzodiazepine dimers bearing C2 substitutions, including compounds of formula (T): wherein: R2 is CHR2A, and R2A is independently selected from H, R, CO2R, COR, CHO, CO2H, and halo; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo; R7 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo; R8 is independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, NO2, Me3Sn and halo; R is independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; or the compound is a dimer with each monomer being of formula (M), where the R7 groups or R8 groups of each monomer form together a dimer bridge having the formula —X—R″—X— linking the monomers; wherein R″ is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H), and/or aromatic rings, e.g. benzene or pyridine; and each X is independently selected from O, S, or N(H); or any pair of adjacent groups from R6 to R9 together form a group —O—(CH2)p—O—, where p is 1 or 2, and salts and solvates thereof, and their use as intermediates for the preparation of other PBD compounds.
摘要翻译：本发明涉及某些吡咯并苯并二氮杂（PBD），特别是含有C2取代的吡咯并苯并二氮杂二聚体，包括式（T）化合物：其中：R2为CHR2A，R2A独立地选自H，R，CO2R，COR，CHO，CO2H ，和卤素; R 6和R 9独立地选自H，R，OH，OR，SH，SR，NH 2，NHR，NRR'，NO 2，Me 3 Sn和卤素; R 7独立地选自H，R，OH，OR，SH，SR，NH 2，NHR，NRR'，NO 2，Me 3 Sn和卤素; R 8独立地选自H，R，OH，OR，SH，SR，NH 2，NHR，NRR'，NO 2，Me 3 Sn和卤素; R独立地选自任选取代的C 1-12烷基，C 3-20杂环基和C 5-20芳基; 或者化合物是每个单体具有式（M）的二聚体，其中每个单体的R 7基团或R 8基团一起形成具有式-X-R“-X-连接单体的二聚体桥; 其中R“是C 3-12亚烷基，该链可被一个或多个杂原子间隔，例如。 O，S，N（H）和/或芳环，例如。苯或吡啶; 并且每个X独立地选自O，S或N（H）; 或从R6至R9的任何一对相邻基团一起形成-O-（CH 2）p -O-基团，其中p为1或2，以及其盐和溶剂化物，以及它们作为制备其它PBD化合物的中间体的用途。

6. 发明授权

US07612062B2 Pyrrolobenzodiazepines 有权
标题翻译：吡咯并苯并二氮杂卓
公开(公告)号：US07612062B2
公开(公告)日：2009-11-03
申请号：US11911890
申请日：2006-04-21
申请人： Stephen John Gregson , Philip Wilson Howard , Zhizhi Chen
发明人： Stephen John Gregson , Philip Wilson Howard , Zhizhi Chen
IPC分类号： C07D519/00 , A61K31/5517 , A61P35/00
CPC分类号： C07D519/00
摘要： Compounds of the formula: (I) or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo; where R and R′ are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR′, nitro, Me3Sn and halo; R″ is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2′, R6′, R7′, R9′, X′ and M′ are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M′ may together represent a divalent pharmaceutically acceptable cation.
摘要翻译：式（I）或其溶剂化物的化合物，其中：R 2是任选取代的C 5-20芳基; R 6和R 9独立地选自H，R，OH，OR，SH，SR，NH 2，NHR，NRR'，硝基，Me 3 Sn和卤素; 其中R和R'独立地选自任选取代的C 1-12烷基，C 3-20杂环基和C 5-20芳基; R 7选自H，R，OH，OR，SH，SR，NH 2，NHR，NHRR'，硝基，Me 3 Sn和卤素; R“是C3-12亚烷基，该链可被一个或多个杂原子和/或芳环中断; X选自O，S或NH; z为2或3; M是一价药学上可接受的阳离子; R 2'，R 6'，R 7'，R 9'，X'和M'分别选自与R 2，R 6，R 7，R 9，X和M相同的基团，或M和M'可以一起表示二价药学上可接受的阳离子。

7. 发明申请

US20080167293A1 Pyrrolobenzodiazepines 有权
标题翻译：吡咯并苯并二氮杂卓
公开(公告)号：US20080167293A1
公开(公告)日：2008-07-10
申请号：US11911890
申请日：2006-04-21
申请人： Philip Wilson Howard , Zhizhi Chen , Stephen John Gregson
发明人： Philip Wilson Howard , Zhizhi Chen , Stephen John Gregson
IPC分类号： A61K31/5513 , C07D487/00 , A61P35/00
CPC分类号： C07D519/00
摘要： Compounds of the formula: (I) or solvate thereof, wherein: R2 is an optionally substituted C5-20 aryl group; R6 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo; where R and R′ are independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR′, nitro, Me3Sn and halo; R″ is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms and/or aromatic rings; X is selected from O, S, or NH; z is 2 or 3; M is a monovalent pharmaceutically acceptable cation; R2′, R6′, R7′, R9′, X′ and M′ are selected from the same groups as R2, R6, R7, R9, X and M respectively, or M and M′ may together represent a divalent pharmaceutically acceptable cation.
摘要翻译：式（I）或其溶剂合物的化合物，其中：R 2是任选取代的C 5-20芳基; R 6和R 9独立地选自H，R，OH，OR，SH，SR，NH 2，NHR，NRR'，硝基，Me 3 Sn和卤素; 其中R和R'独立地选自任选取代的C 1-12烷基，C 3-20 - 杂环基和C 5-20芳基 ; R 7选自H，R，OH，OR，SH，SR，NH 2，NHR，NHRR'，硝基，Me 3 Sn和卤素; R“是C 3-12亚烷基，该链可以被一个或多个杂原子和/或芳环中断; X选自O，S或NH; z为2或3; M是一价药学上可接受的阳离子; R 2，R 6，R 7，R 9，X'和M'分别为分别选自与R 2，R 6，R 7，R 9，X和M分别相同的基团，或M和M'可以一起表示二价药学上可接受的阳离子。

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