Pyrrolobenzodiazepines
View Patent ↗A compound of formula (I) and salts and solvates thereof, wherein: R 10 is a nitrogen protecting group and R 11 is either OH or O—R 12 , wherein R 12 is an oxygen protecting group, or R 10 and R 11 together form a double bond between N10 and C11; and R 10′ and R 11′ are selected from the same options as R 10 and R 11 respectively.
1. A compound of formula I:
or a pharmaceutically acceptable salt thereof, wherein:
R 10 and R 11 together form a double bond between N10 and C11 or wherein R 10 is H and R 11 is OH or ORA, RA being C 1-7 alkyl;
and R 10′ and R 11′ are selected from the same options as R 10 and R 11 respectively.
2. A compound of formula I:
wherein:
R 10 is a nitrogen protecting group and R 11 is either OH or O—R 12 , wherein R 12 is an oxygen protecting group;
and R 10′ and R 11′ are selected from the same options as R 10 and R 11 respectively.
3. A compound according to claim 2 , wherein the compounds have the following stereochemistry at the C11 position:
4. A compound according to claim 2 , wherein the nitrogen protecting groups are selected from carbamate nitrogen protecting groups.
5. A compound according to claim 4 , wherein the nitrogen protecting groups are selected from the group consisting of Alloc, Troc, Teoc, BOC, Doc, Hoc, TcBOC, Fmoc, 1-Adoc and 2-Adoc.
6. A compound according to claim 1 , wherein at least 50% is in either the E-, E- or Z-, Z-forms.
7. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.
8. A method for the treatment of an infection, comprising administering to a subject suffering from an infection a therapeutically-effective amount of a compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein the infection is by gram-positive bacteria.
9. The method of claim 8 , wherein the gram-positive bacteria is selected from MRSA and VRE.