| abstract |
The invention relates to pyrridinobenzodiazepines (PDDs) comprising three fused 6- 7 -6-membered rings linked to aromatic groups, and pharmaceutically acceptable salts thereof, which are useful as medicaments, such as anti-proliferative agents. PDDs may be represented by formula (I): and salts and solvates thereof, wherein the dotted lines indicates the optional presence of a double bond between one or more of Ci and C 2 , C 2 and C 3 , and C 3 and C 4 ; R1 and R2 are substituent groups; R3 is selected from H, C1-12 alkyl and CH2Ph; R 4 is selected from phenyl and C 5 - 9 heteroaryl groups optionally substituted, with the proviso that the optionally substituted C 5 - 9 heteroaryl is not indolyl; R1 9 is selected from H and (CH2) t -NR 20 R 21 ; Y i is N or CH; Y2 is N or CH; and wherein at least one of Y 1 and Y2 is CH; p is o or 1 ; X 1 is a connecting group; L is a linker group; X2 is a connecting group or is absent; q is selected from o, 1, 2, 3,4,5 and 6; A is selected from: for each Ai group one of Y 3 and Y 4 is selected from N-R 17 ,S and O; and the other of Y 3 and Y 4 is CH; and Y 5 is selected from CH, N, S and COH; for each A 2 group one of Y 6 and Y 7 is independently selected from N and CH; and the other of Y 6 and Y 7 is CH; R1 3 , R1 4 , R 17 , R2 o and R2 i are independently selected from H and C 1-6 alkyl; and either: (i) R 5 and R 6 together form a double bond; (ii) R 5 is H and R 6 is OH; or (iii) R 5 is H and R 6 is OC 1-6 alkyl; with the proviso that when p is o and A is Ai, then: (a) for at least one Ai group one of Y 3 and Y 4 is selected from S and O; or (b) for at least one Ai group Y 5 is S; or (c) R 4 is not pyrrolyl, imidazolyl, optionally substituted pyrrolyl or optionally substituted imidazolyl. |