HOWARD, PHILIP WILSON,FLYGARE, JOHN A.,PILLOW, THOMAS,WEI, BINQING
申请号：
CA2904044
公开号：
CA2904044A1
申请日:
2014.03.13
申请国别(地区):
CA
年份:
2014
代理人:
摘要：
A conjugate of formula A wherein: D represents either group D1 or D2 the dotted line indicates the optional presence of a double bond between C2 and C3； when there is a double bond present between C2 and C3, R2 is selected from the group consisting of: (ia) C5-10 aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, carboxy, ester, C1-7 alkyl, C3-7 heterocyclyl and bis-oxy-C1-3 alkylene； (ib) C1-5 saturated aliphatic alkyl； (ic) C3-6 saturated cycloalkyl； (id) wherein each of R31, R32 and R33 a, re independently selected from H, C1-3 saturated alkyl, C2-3 alkenyl, C2-3 alkynyl and cyclopropyl, where the total number of carbon atoms in the R2 group is no more than 5； (ie) wherein one of R35a and R35b is H and the other is selected from: phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy； pyridyl； and thiophenyl； and (if) where R34 is selected from: H； C1-3 saturated alkyl； C2-3 alkenyl； C2-3 alkynyl； cyclopropyl； phenyl, which phenyl is optionally substituted by a group selected from halo, methyl, methoxy； pyridyl； and thiophenyl； (ig) halo； when there is a single bond present between C2 and C3, 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 R16a and R16b is H, the other is selected from nitrile and a C1-4 alkyl ester； D' represents either group D'1 or D2: wherein the dotted line indicates the optional presence of a double bond between C2' and C3'； 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
