1599447-61-6Relevant articles and documents
UNSYMMETRICAL PYRROLOBENZODIAZEPINES-DIMERS FOR USE IN THE TREATMENT OF PROLIFERATIVE AND AUTOIMMUNE DISEASES
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, (2014/07/08)
A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: R2 is of formula (IIa), formula (IIb) or formula (IIc): (a) where A is a C5-7 aryl group, and either (i) Q1 is a single bond, and Q2 is selected from a single bond and -Z-(CH2)n-, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q1 is -CH=CH-, and Q2 is a single bond; (b) where: RC1, RC2 and RC3 are independently selected from H and unsubstituted C1-2 alkyl; (c) where Q is selected from OH, SH and NRN, and RN is selected from H, methyl and ethyl X is selected from the group comprising: OH, SH, CO2H, COH, N=C=O, NHNH2, CONHNH2, (formula (x)), (formular (y), NHRN, wherein RN is selected from the group comprising H and C1-4 alkyl; and either: when there is a double bond present between C2' and C3', R12 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 R21, R22 and R23 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 R12 group is no more than 5; (ie), wherein one of R25a and R25b 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 R24 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; when there is a single bond present between C2' and C3', R12 is (formula (z)), where R26a and R26b 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 R26a and R26b is H, the other is selected from nitrile and a C1-4 alkyl ester; R6 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 C1-12 alkyl, C3-20 heterocyclyl and C5-20 aryl groups; R7 is selected from H, R, OH, OR, SH, SR, NH2, NHR, NHRR', nitro, Me3Sn and halo; R is a C3-12 alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, NRN2 (where RN2 is H or C1-4 alkyl), and/or aromatic rings, e.g. benzene or pyridine; Y and Y' are selected from O, S, or NH; R6', R7', R9' are selected from the same groups as R6, R7 and R9 respectively; either: (A) R20 is H or Me and R21a and R21b are both H or together form =O and either: (i) R10 is H, R11a is H and R11b is OH or ORA, where RA is C1-4 alkyl; or (ii) R10 and R11b form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound and R11a is H; or (iii) R10 is H, R11a is H and R11b is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; or (B) R10 is H or Me and R11a and R11b are both H or together form =O and either: (i) R20 is H, R21a is H and R21b is OH or ORA, where RA is C1-4 alkyl; or (ii) R20 and R21b form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound and R11a is H; or (iii) R20 is H, R21a is H and R21b is SOzM, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation.
