FIELD: chemistry.
SUBSTANCE: invention relates to novel bifunctional CTI-CTI and CBI-CTI dimers of formula F1-L1-TL2-F2, each of F1 and F2 is independently selected from ring systems A, B, C and D:
(Ring system A)
(Ring system B)
(Ring system C)
(Ring system D),
where each R is independently selected from a group consisting of H, -C1-C20alkyl, -C2-C6alkenyl, -C2-C6alkynyl, halogen, hydroxyl, alkoxy, -NH2, -NH(C1-C8alkyl), -N(C1-C8alkyl)2, -NO2, -C6-C14aryl and -C6-C14heteroaryl, where two or more R are possibly connected to form a ring or rings and where said -C6-C14aryl and -C6-C14heteroaryl is optionally substituted with 1-5 substituents, independently selected from -C1-C10alkyl, -C1-C10alkoxy, -halogen, -C1-C10alkylthio, -trifluoromethyl, -NH2, -NH(C1-C8alkyl), -N(C1-C8alkyl)2, -C1-C10alkyl-N(C1-C8alkyl)2, -C1-C3alkylthio, -NO2 or -C1-C10heterocyclyl, for each ring system in which there is R; each V1 independently represents a bond, O, N(R) or S for each ring system, in which there is V1; each V2 independently represents O, N(R) or S for each ring system, in which there is V2; each of W1 and W2 independently represents H or -C1-C5alkyl for each ring system, in which there are W1 and W2; each X independently represents -OH, -O-acyl, azido, halogen, cyanate, thiocyanate, isocyanate, thioisocyanate or 
for each ring system in which there is X; each Y is independently selected from a group consisting of H, -C1-C6alkyl-RA, -C(O)RA, -C(S)RA, -C(O)ORA, -S(O)2ORA, -C(O)N(RA)2, -C(S)N(RA)2, glycosyl, -NO2 and -PO(ORA)2, for each ring system, in which there is Y, where each RA is independently selected from a group consisting of H, -C1-C20alkyl, -C1-C8heteroalkyl, -C6-C14aryl, aralkyl, -C1-C10heterocyclyl, -C3-C8carbocyclyl and -C1-C20alkyl N(R)2, where said -C1-C20alkyl, -C1-C8heteroalkyl, -C6-C14aryl, aralkyl, -C1-C10heterocyclyl, -C3-C8carbocyclyl and -C1-C20alkyl N(R)2 optionally substituted with 1-3 substitutes independently selected from R; each Z is independently selected from a group consisting of H and -C1-C8alkyl, optionally substituted with 1-3 substitutes independently selected from R, for each ring system in which Z is available; each of L1 and L2 independently represents a direct link; T is selected from -C(A1)X1-T2-X1C (B1)-.
EFFECT: compounds are useful for treating proliferative diseases, where the inventive dimers can function as self-contained drugs, useful loads in antibody-drug conjugates (ADC) and linker-useful load compounds.
31 cl, 10 tbl
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