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    • 1. 发明申请
      WO2013055987A1 PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF 审中-公开
    • PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
    • 。。。。。。。。。。。。
    • WO2013055987A1
    • 2013-04-18
    • PCT/US2012/059864
    • 2012-10-12
    • SPIROGEN SÀRL , GENENTECH, INC.
    • FLYGARE, John, A. , GUNZNER-TOSTE, Janet, L. , PILLOW, Thomas , HOWARD, Philip, Wilson , MASTERSON, Luke
    • A61K47/48 , C07D487/04 , C07D519/00 , A61P35/00
    • A61K47/48384 , A61K47/6803 , A61K47/6849 , C07D487/04 , C07D519/00
    • A conjugate of formula (A): the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R 2 is independently selected from H, OH, =0, =CH 2 , CN, R, OR, =CH-R D , =C(R D ) 2 , 0-S0 2 -R, C0 2 R and COR, and optionally further selected from halo or dihalo; where R D is independently selected from R, C0 2 R, COR, CHO, C0 2 H, and halo; R 6 and R 9 are independently selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR', NO 2, Me 3 Sn and halo; R 7 is independently selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR', N02, Me 3 Sn and halo; Y is selected from a single bond, and a group of formulae A1 or A2: where N shows where the group binds to the N10 of the PBD moiety; R L1 and R L2 are independently se!ected from H and methyl, or together with the carbon atom to which they are bound form a cyclopropylene group; CBA represents a cell binding agent; Q is independently selected from O, S and NH; R 11 is either H, or R or, where Q is O, S0 3 M, where M is a metal cation; R and R' are each independently selected from optionally substituted C 1-12 alkyl, C 3-20 heterocyclyl and C 5-20 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 Z-metfibered heteracyciie ring; wherein R 12 R 16 , R 19 and R 17 are as defined for R 2 , R 6 , R 9 and R 7 respectively: wherein R" is a C 3-12 alky!ene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H}; NMe and/or aromatic rings, e.g. benzene or pyridine, which rings are optional y substituted; X and X' are independently selected from O, S and N(H).
    • 式（A）的缀合物：虚线表示在C1和C2或C2和C3之间任选存在双键; R2独立地选自H，OH，= O，= CH2，CN，R，OR，= CH-RD，= C（RD）2,0-SO2-R，CO 2 R和COR，并且任选地进一步选自卤素或 二卤; 其中RD独立地选自R，CO 2 R，COR，CHO，CO 2 H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; Y选自单键和式A1或A2的基团：其中N表示基团结合PBD部分的N10的位置; RL1和RL2独立地由H和甲基取代，或与它们所结合的碳原子一起形成环亚丙基; CBA代表细胞结合剂; Q独立地选自O，S和NH; R 11是H或R，或其中Q是O，SO 3 M，其中M是金属阳离子; 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，并且任选地相对于NRR'基团，R和R'与它们所连接的氮原子一起形成 任选取代的4-，5- 6-或Z-元纤维杂化环; 其中R 12 R 16，R 19和R 17分别如对R 2，R 6，R 9和R 7所定义：其中R“为C 3-12烷基，该链可以被一个或多个杂原子（例如O，S，N H}; NMe和/或芳环，例如苯或吡啶，该环是任选的y取代的; X和X'独立地选自O，S和N（H）。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
    • 4. 发明公开
      EP2750713A1 PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF 有权 转让
    • PYRROLOBENZODIAZEPINES AND CONJUGATES THEREOF
    • 吡咯并苯并二氮杂及其偶联物
    • EP2750713A1
    • 2014-07-09
    • EP12780356.7
    • 2012-10-12
    • Spirogen Sàrl
    • FLYGARE, John, A. , GUNZNER-TOSTE, Janet, L. , PILLOW, Thomas , HOWARD, Philip, Wilson , MASTERSON, Luke
    • A61K47/48 , C07D487/04 , C07D519/00 , A61P35/00
    • A61K47/48384 , A61K47/6803 , A61K47/6849 , C07D487/04 , C07D519/00
    • A conjugate of formula (A): the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3; R
      2 is independently selected from H, OH, =0, =CH
      2 , CN, R, OR, =CH-R
      D , =C(R
      D )
      2 , 0-S0
      2 -R, C0
      2 R and COR, and optionally further selected from halo or dihalo; where R
      D is independently selected from R, C0
      2 R, COR, CHO, C0
      2 H, and halo; R
      6 and R
      9 are independently selected from H, R, OH, OR, SH, SR, NH
      2 , NHR, NRR', NO
      2, Me
      3 Sn and halo; R
      7 is independently selected from H, R, OH, OR, SH, SR, NH
      2 , NHR, NRR', N02, Me
      3 Sn and halo; Y is selected from a single bond, and a group of formulae A1 or A2: where N shows where the group binds to the N10 of the PBD moiety; R
      L1 and R
      L2 are independently se!ected from H and methyl, or together with the carbon atom to which they are bound form a cyclopropylene group; CBA represents a cell binding agent; Q is independently selected from O, S and NH; R
      11 is either H, or R or, where Q is O, S0
      3 M, where M is a metal cation; R and R' are each independently selected from optionally substituted C
      1-12 alkyl, C
      3-20 heterocyclyl and C
      5-20 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 Z-metfibered heteracyciie ring; wherein R
      12 R
      16 , R
      19 and R
      17 are as defined for R
      2 , R
      6 , R
      9 and R
      7 respectively: wherein R" is a C
      3-12 alky!ene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, N(H}; NMe and/or aromatic rings, e.g. benzene or pyridine, which rings are optional y substituted; X and X' are independently selected from O, S and N(H).
    • 式（A）的缀合物：虚线表示C1和C2或C2和C3之间任选存在双键; R 2独立地选自H，OH，= O，= CH 2，CN，R，OR 1，= CH-R D，= C（RD）2，SO 2 2 -R，CO 2 R和COR， 进一步选自卤代或二卤代; 其中R D独立地选自R，CO 2 R，COR，CHO，CO 2 2H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; Y选自单键和式A1或A2的基团：其中N表示基团与PBD部分的N10结合的位置; R L1和R L2独立地选自H和甲基，或与它们所键合的碳原子一起形成亚环丙基; CBA代表细胞结合剂; Q独立地选自O，S和NH; R 11是H或R，或者，其中Q是O，SO 3 M，其中M是金属阳离子; 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'以及它们所连接的氮原子一起 从任选取代的4-，5-; 6-或Z-元素的heteracyciie环; 其中R 12，R 16，R 19和R 17分别如对于R 2，R 6，R 9和R 7所定义：其中R“是C 3-12炔基，该链可以被一个或多个 杂原子，例如O，S，N（H）; NMe和/或芳香环，例如苯或吡啶，这些环是可选和/或取代的; X和X'独立地选自O，S和N（H）。
    • 基本信息 添加关注 加入工作空间 PDF全文 PDF下载 全文下载 相似专利 双屏查看 权利要求书 说明书全文 Global Dossier Espacenet 法律信息 同族专利 专利引用
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