C8, c8' linked 5-oxo-1,2,3,11a-tetrahydro-5h-pyrrolo[2,1-c][1,4] benzodiazepine dimers with 1h-pyrrole-dicarboxylic acid amide linkers and oligomeric analogs therof as well as related compounds for the treatment of proliferative diseases

A compound of formula (I):

• PBD-A-Y—X—(Het)na-L-(Het)nb-L-(Het)nc-T-(Het′)nd-L-(Het′)ne-L-(Het′)nf—X′—Y′-A′-PBD′ (I)
• and salts, solvates, chemically protected forms, and prodrugs thereof, wherein
• with the bonds at the 8 position on each molecule bond to the A and A′ groups respectively.
• the dotted lines indicate the optional presence of a double bond between C1 and C2 or C2 and C3;
• R2 and R3 are independently selected from —H, —OH, ═O, ═CH2, —CN, —R, OR, halo, ═CH—R, O—SO2—R, CO2R and COR;
• R6, R7 and R9 are independently selected from H, R, OH, OR, SH, SR, NH2, NHR, NRR′, nitro, Me3Sn and halo;
• where R and R′ are independently selected from optionally substituted C1-7 alkyl, C3-20 heterocyclyl and C5-20 aryl groups;
• or
• R6 and R7 together form a group —O—(CH2)p—O—, where p is 1 or 2;
• R10 is a nitrogen protecting group and R15 is either O—R11, where R11 is a hydroxyl protecting group;
• or
• R15 is OH, ═O or ═S;
• or
• R10 and R15 together form a double bond between C10 and N11;
• A is selected from O, S, NH or a single bond;
• Y is a divalent group such that HY═R, or a single bond;
• X and X′ are both either NH or C(═O);
• each Het and Het′ is independently an amino-heteroarylene-carbonyl group;
• each L is independently selected from β-alanine, glycine, 4-aminobutanoic acid and a single bond;
• T is a divalent linker group of the form:
• —NH-Q-NH— or —C(═O)-Q-C(═O)—
• wherein Q is a divalent group such that HQ=R;
• A′, Y′, Het′, R2′, R3′, R6′, R7′, R9′, R10′, R11′, R15′ and R15′ are all independently selected from the same lists as previously defined for A, Y, Het, R2, R3, R6, R7, R9, R10, R11 and R15 respectively;
• na, nb, nc, nd, ne and nf are each independently 0 to 5 and the sum na+nb+nc+nd+ne+nf is 0 to 16.