Patent WO-2014096365-A1 (WO)
Title: Unsymmetrical pyrrolobenzodiazepines-dimers for use in the treatment of proliferative and autoimmune diseases
Inventor: HOWARD PHILIP WILSON
IPC: A61P19/00
Filed: 2013-12-20
Abstract: A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: R 2  is of formula (IIa), formula (IIb) or formula (IIc): (a) where A is a C 5-7  aryl group, and either (i) Q 1  is a single bond, and Q 2  is selected from a single bond and -Z-(CH 2 ) n -, where Z is selected from a single bond, O, S and NH and n is from 1 to 3; or (ii) Q 1  is -CH=CH-, and Q 2  is a single bond; (b) where: R C1 , R C2  and R C3  are independently selected from H and unsubstituted C 1-2  alkyl; (c) where Q is selected from OH, SH and NR N , and R N  is selected from H, methyl and ethyl X is selected from the group comprising: OH, SH, CO 2 H, COH, N=C=O, NHNH 2 , CONHNH 2 , (formula (x)), (formular (y), NHR N , wherein R N  is selected from the group comprising H and C 1-4  alkyl; and either: when there is a double bond present between C2' and C3', R 12  is selected from the group consisting of: (ia) C 5-10  aryl group, optionally substituted by one or more substituents selected from the group comprising: halo, nitro, cyano, ether, carboxy, ester, C 1-7  alkyl, C 3-7  heterocyclyl and bis-oxy-C 1-3  alkylene; (ib) C 1-5  saturated aliphatic alkyl; (ic) C 3-6  saturated cycloalkyl; (id), wherein each of R 21 , R 22  and R 23  are independently selected from H, C 1-3  saturated alkyl, C 2-3  alkenyl, C 2-3  alkynyl and cyclopropyl, where the total number of carbon atoms in the R 12  group is no more than 5; (ie), wherein one of R 25a  and R 25b  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 R 24  is selected from: H; C 1-3  saturated alkyl; C 2-3  alkenyl; C 2-3  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', R 12  is (formula (z)), where R 26a  and R 26b  are independently selected from H, F, C 1-4  saturated alkyl, C 2-3  alkenyl, which alkyl and alkenyl groups are optionally substituted by a group selected from C 1-4  alkyl amido and C 1-4  alkyl ester; or, when one of R 26a  and R 26b  is H, the other is selected from nitrile and a C 1-4  alkyl ester; R 6  and R 9  are independently selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NRR', nitro, Me 3 Sn and halo; where R and R' are independently selected from optionally substituted C 1-12  alkyl, C 3-20  heterocyclyl and C 5-20  aryl groups; R 7  is selected from H, R, OH, OR, SH, SR, NH 2 , NHR, NHRR', nitro, Me 3 Sn and halo; R" is a C 3-12  alkylene group, which chain may be interrupted by one or more heteroatoms, e.g. O, S, NR N2  (where R N2  is H or C 1-4  alkyl), and/or aromatic rings, e.g. benzene or pyridine; Y and Y' are selected from O, S, or NH; R 6' , R 7' , R 9'  are selected from the same groups as R 6 , R 7  and R 9  respectively; either: (A) R 20  is H or Me and R 21a  and R 21b  are both H or together form =O and either: (i) R 10  is H, R 11a  is H and R 11b  is OH or OR A , where R A  is C 1-4  alkyl; or (ii) R 10  and R 11b  form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound and R 11a  is H; or (iii) R 10  is H, R 11a  is H and R 11b  is SO z M, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation; or (B) R 10  is H or Me and R 11a  and R 11b  are both H or together form =O and either: (i) R 20  is H, R 21a  is H and R 21b  is OH or ORA, where R A  is C 1-4  alkyl; or (ii) R 20  and R 21b  form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound and R 11a  is H; or (iii) R 20  is H, R 21a  is H and R 21b  is SO z M, where z is 2 or 3 and M is a monovalent pharmaceutically acceptable cation.