利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

20 条记录 (耗时 0.018 秒)

    PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
    2.
    发明公开
    PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF 审中-公开
    吡咯并苯并二氮杂及其偶联物

    公开(公告)号：EP2968596A2

    公开(公告)日：2016-01-20

    申请号：EP14761432.5

    申请日：2014-03-13

    申请人： MEDIMMUNE LIMITED ,  Genentech, Inc.

    发明人： HOWARD, Philip, Wilson ,  FLYGARE, John, A. ,  PILLOW, Thomas ,  WEI, Binqing

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

    CPC分类号： A61K47/6869 ,  A61K31/5517 ,  A61K47/6803 ,  A61K47/6851 ,  A61K47/6855 ,  A61K47/6889 ,  A61P35/00 ,  C07D487/04 ,  C07D487/16 ,  C07D519/00

    摘要： Conjugate compounds of formula (A): wherein: R2 is where R36a and R36b are independently selected from H, F, C1-4 saturated alkyl, C2-3 alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C1-4 alkyl amido and C1-4 alkyl ester or, when one of R36a and R36b is H, the other is selected from nitrile and a C1-4 alkyl ester; 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; Y is selected from formulae A1, A2, A3, A4, A5 and A6: L is a linker connected to a cell binding agent; CBA is the cell binding agent; n is an integer selected in the range of 0 to 48; RA4 is a C1-6 alkylene group; either (a) R10 is H, and R11 is OH, ORA, where RA is C1-4 alkyl; or (b) R10 and R11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound; or (c) R10 is H and R11 is OSOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; R and R′ are each independently selected from optionally substituted C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups, and optionally in relation to the group NRR′, R and R′ together with the nitrogen atom to which they are attached form an optionally substituted 4-, 5-, 6- or 7-membered heterocyclic ring; wherein R16, R17, R19, R20, R21 and R22 are as defined for R6, R7, R9, R10, R11 and R2 respectively; wherein Z is CH or N; wherein T and T′ are independently selected from a single bond or a C1-9 alkylene, which chain may be interrupted by one or more heteroatoms e.g. O, S, N(H), NMe, provided that the number of atoms in the shortest chain of atoms between X and X′ is 3 to 12 atoms; and X and X′ are independently selected from O, S and N(H).

    摘要翻译： 式（A）的偶联化合物：其中：R 2是，其中：R 36a和R 36b独立地选自H，F，C 1-4饱和烷基，C 2-3烯基，其中烷基和烯基任选被 选自C 1-4烷基酰胺基和C 1-4烷基酯的基团; 或者当R 36a和R 36b中的一个是H时，另一个选自腈和C 1-4烷基酯; 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; Y选自式A1，A2，A3，A4，A5和A6：L是与细胞结合剂连接的接头; CBA是细胞结合剂; n是在0至48范围内选择的整数; R A4是C 1-6亚烷基; （a）R 10为H，且R 11为OH，OR A，其中R A为C 1-4烷基; 或（b）R 10和R 11在它们所键合的氮原子和碳原子之间形成氮 - 碳双键; 或（c）R 10为H且R 11为OSO zM，其中z为2或3且M为单价药学上可接受的阳离子; R和R'各自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，并且任选地与基团NRR'，R和R'一起与氮原子一起形成 它们连接形成任选取代的4-，5-，6-或7-元杂环; 其中R 16，R 17，R 19，R 20，R 21和R 22分别与R 6，R 7，R 9，R 10，R 11和R 2的定义相同; 其中Z是CH或N; 其中T和T'独立地选自单键或C 1-9亚烷基，该链可被一个或多个杂原子例如 O，S，N（H），NMe，条件是在X和X'之间的最短原子链中的原子数是3至12个原子; X和X'独立地选自O，S和N（H）。