Pyrrolobenzodiazepines used to treat proliferative diseases
View Patent ↗Pyrrolobenzodiazepine dimers I having a C2-C3 double bond and an aryl group at the C2 position on one monomer unit, and a C2-C3 double bond and either a conjugated double or triple bond at the C2 position or an alkyl group at the C2 position on the other monomer unit, and conjugates of these compounds.
1. A compound with the formula I:
wherein:
R 2 is of formula III:
Where A is —C 6 H 4 —, X is NHR N , wherein R N is H, and Q 1 is a single bond, and Q 2 is a single bond;
R 12 is selected from:
(iia) methyl;
(iib) cyclopropyl;
(iic)
wherein R 21 and R 22 are hydrogen and R 23 is methyl;
(iid)
wherein R 25b is H and R 25a is phenyl; and
(iie)
wherein R 24 is H;
R 6 and R 9 are H;
Where R is independently selected from optionally substituted C 1-12 alkyl, C 3-20 heterocyclyl and C 5-20 aryl groups;
R 7 is OH or OR;
R 10 and R 11 form a nitrogen-carbon double bond between the nitrogen and carbon atoms to which they are bound;
R″ os a C 3 alkylene group;
Y and Y′ are O;
R 6 , R 7 ′, R 9 ′ are selected from the same groups as R 6 , R 7 , and R 9 respectively and R 10 ′ and R 11 ′ are the same as R 10 and R 11 .
2. A compound according to claim 1 , with the structure:
3. A compound according to claim 1 , wherein R 12 is methyl.
4. A compound according to claim 1 , wherein R 12 is cyclopropyl.
5. A compound according to claim 1 , wherein R 12 is
and R 21 and R 22 are H and R 23 is methyl.
6. A compound according to claim 1 , wherein R 12 is
and R 25a is phenyl and R 25b is H.
7. A compound according to claim 1 , wherein R 12 is
and R 24 is H.