Pyrrolobenzodiazepines and conjugates thereof

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 are 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,
• 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;
• Z is N or CH;
• D′ represents either group D′1 or D′2:
• 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 of formula A1:
• RN1 is selected from H and C1-4 alkyl;
• 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;
• Q is:
• where QX is such that Q is an amino-acid residue, a dipeptide residue or a tripeptide residue;
• 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 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).