HOWARD, PHILIP WILSON,FLYGARE, JOHN A.,PILLOW, THOMAS,WEI, BINQING
申请号：
CA2901941
公开号：
CA2901941A1
申请日:
2014.03.13
申请国别(地区):
CA
年份:
2014
代理人:
摘要：
Conjugate compounds of formula (A): wherein: R2 is, where R36a and R36b are independently selected from H, F, C1-4 saturated aikyl, 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 aikyl 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 aikyl； 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).
