Pyrrolobenzodiazepines

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

the dotted double bond indicates the presence of a single or double bond between C2 and C3;

R 2 is selected from —H, —OH, =0, ═CH 2 , —CN, —R, OR, halo, dihalo, ═CHR, ═CHRR′, —O—SO 2 —R, CO 2 R and COR;

R 7 is 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 1-7 alkyl, C 2-7 alkenyl, C 2-7 alkynyl, C 3-7 cycloalkyl, C 3-20 heterocyclyl and C 5-20 aryl groups, wherein the optional substituents are selected from

—F, —Cl, —Br, —I, —OH, —OR 24 , —CH(OR 21 )(OR 21 ), —CH(OH)(OR 21 ), —CR(OR 21 )(OR 21 ), ═O, ═S, ═NR 22 , —C(═O)R 21 , —C(═O)OH, —C(═S)SH, —C(═O)SH, —C(═S)OH, —C(═NH)OH, —C(═NOH)OH, —C(═O)OR 21 , —OC(═O)R 21 , —OC(═O)OR 21 , —NR 23 R 23 , —C(═O)NR 23 R 23′ , —C(═S)NR 23 R 23′ , —NR 22 C(═O)R 21 , —OC(═O)NR 23 R 23′ , —N(R 22 )CONR 23 R 23′ , —NH—C(═NH)NH 2 , ═NR 22 , —C(═NR 22 )N(R 22 ) 2 , —NO 2 , —NO, —N 3 , —CN, —NC, —OCN, —NCO, —SCN, —NCS, —SH, —SR 21 , —SS—R 21 , —S(═O)R 21 , —S(═O)R 21 , —S(═O)OH, —S(═O) 2 OH, —S(═O)OR 21 , —S(═O) 2 OR 21 , —OS(═O)R 21 , —OS(═O)R 21 , —OS(═O) 2 OR 21 , —S(═O)NR 23 R 23′ , —S(═O) 2 NR 23 R 23′ , —NR 22 S(═O) 2 OH, —NR 22 S(═O) 2 R 21 , —NR 22 S(═O)R 21 , —PR 22 2 , —P(═O) 2 , —P(═O)(R 21 ) 2 , —P(═O)(OH) 2 , —P(═O)(OR 22 ) 2 , —OP(═O)(OH) 2 , —OP(═O)(OR 22 ) 2 , —OP(OH) 2 , —OP(OR 22 ) 2 , —OP(OR 22 )—N(R 22 ) 2 ; and —OP(═O)(OR 22 )—N(R 22 ) 2 wherein

each R 21 is independently selected from C 1-7 alkyl, a C 3-20 heterocyclyl, or a C 5-20 aryl;

each R 22 is independently selected from hydrogen C 1-7 alkyl, a C 3-20 heterocyclyl or a C 5-20 aryl;

each R 23 is independently selected from hydrogen C 1-7 alkyl a C 3-20 heterocyclyl a C 5-20 or, in the case of a “cyclic” amino group, R 23 and R 23′ , taken together with the nitrogen atom to which they are attached, form a heterocyclic ring having from 4 to 8 ring atoms;

each R 24 is independently alkyl; and

each R 25 is independently selected from optionally substituted C 1-7 alkyl a C 3-20 heterocyclyl, or a C 5-20 aryl;

R 10 and R 11 either together form a double bond, or are selected from H and QR Q respectively, where Q is selected from O, S and NH and R Q is H or C 1-7 alkyl or H and SO X M, where x is 2 or 3, and M is a monovalent pharmaceutically acceptable cation;

A is selected from A1, A2, A3, A4 or A5:

Where

X 1 and Y 1 are selected from: CH and NH; CH and NMe; N and NMe; CH and S; N and S; N and O; and CH and O, respectively;

X 2 and Y 2 are selected from: CH and NH; CH and NMe; N and NMe; CH and S;

N and S; N and O; and CH and O, respectively;

Z 1 is selected from O and S;

Z 2 is selected from CH and N;

F is selected from a single bond and -(E-F 1 ) m —;

each E is independently selected from a single bond, and —C(═O)—NH—;

each F 1 is independently a C 5-20 heteroarylene group;

m is 1, 2 or 3;

G is selected from hydrogen, C 1-4 alkyl, —C(═O)—O—C 1-4 alkyl, —(CH 2 ) n —C 3-20 heterocyclyl, and —O—(CH 2 ) n —C 3-20 heterocyclyl group;

each n is 0-4;

wherein C 3-20 heterocyclyl pertains to a monovalent moiety obtained by removing a hydrogen atom from a ring atom of a heterocyclic compound, which moiety has from 3 to 20 rings atoms, of which 1 to 10 are ring heteroatoms selected from N, O and S;

wherein C 5-20 heteroarylene pertains to a divalent moiety obtained by removing a hydrogen atom from each of two ring atoms of a heteroaromatic compound, which moiety has from 3 to 20 rings atoms, of which 1 to 10 are ring heteroatoms selected from N, O and S;

provided that A2 is not A2:

where X 1 and Y 1 of A2′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and

provided that A3 is not A3′:

where X 2 and Y 2 of A3′ are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively;

B is either a single bond or:

where X and Y of B1 are selected from: CH and NMe; COH and NMe; CH and S; N and NMe; N and S, respectively; and

R 1 is C 1-4 alkyl.

2. A compound according to claim 1 , wherein R 7 is OR 7A , where R 7A is optionally substituted C 1-7 alkyl.

3. A compound according to claim 2 , wherein R 7A is selected from Me, CH 2 Ph and allyl.

4. A compound according to claim 1 , wherein R 10 and R 11 form a double bond together.

5. A compound according to claim 1 , wherein R 1 is C 1-2 alkyl.

6. A compound according to claim 5 , wherein R 1 is methyl.

7. A compound according to claim 1 , wherein R 2 is selected from —H, ═CH 2 , —R, ═CHR, and ═CRR′.

8. A compound according to claim 1 , wherein R 2 is of the configuration C1:

9. A compound according to claim 1 , wherein R 2 is selected from optionally substituted phenyl, optionally substituted napthyl, optionally substituted pyridyl, optionally substituted quinolinyl or isoquinolinyl.

10. A compound according to claim 9 , wherein R 2 is selected from 4-methoxy-phenyl, 3-methoxyphenyl, 4-ethoxy-phenyl, 3-ethoxy-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 3,4-bisoxymethylene-phenyl, 4-methylthienyl, 4-cyanophenyl, 4-phenoxyphenyl, quinolin-3-yl and quinolin-6-yl, isoquinolin-3-yl and isoquinolin-6-yl, 2-thienyl, 2-furanyl, methoxynaphthyl, and naphthyl.

11. A compound according to claim 1 , wherein R 2 is selected from:

(a) C 1-5 saturated aliphatic alkyl;

(b) C 3-6 saturated cycloalkyl;

(c)

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;

(d)

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

(e)

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.

12. A compound according to claim 1 , wherein if R 2 is selected from ═O, ═CH 2 , ═CHR, ═CHRR′, there is a single bond between C2 and C3.

13. A compound according to claim 1 , wherein there is no double bond between C2 and C3 and R 2 is H.

14. A compound according to claim 1 , wherein X 1 and Y 1 are selected from N and NMe and CH and NMe, respectively.

15. A compound according to claim 1 , wherein F is -(E-F 1 ) m —, and F 1 is a C 5 heteroarylene group.

16. A compound according to claim 15 , wherein F 1 is represented by structure F11:

wherein X 3 and Y 3 are selected from: CH and O; and CH and NMe, respectively.

17. A compound according to claim 1 , wherein G is selected from the group consisting of —H, -Me, —C(═O)—O-Me, —(CH 2 ) n —N(CH 2 CH 2 OCH 2 CH 2 ), and —O—(CH 2 ) n —N(CH 2 CH 2 OCH 2 CH 2 ).

18. A compound according claim 1 , wherein A is selected from the group consisting of:

wherein in A1:

Z 1 is O, X 1 is CH and Y 1 is NMe;

Z 1 is O, X 1 is N and Y 1 is NMe;

Z 1 is S, X 1 is CH and Y 1 is NMe; or

Z 1 is S, X 1 is N and Y 1 is NMe; and

wherein in A2:

Z 1 is CH, X 1 is CH and Y 1 is NMe;

Z 1 is N, X 1 is N and Y 1 is NMe;

Z 1 is CH, X 1 is N and Y 1 is NMe; or

Z 1 is N, X 1 is CH and Y 1 is NMe; and

wherein in A3:

Y 1 is NMe, X 1 is CH, Y 2 is NMe and X 2 is CH;

Y 1 is NMe, X 1 is CH, Y 2 is NMe and X 2 is N;

Y 1 is NMe, X 1 is N, Y 2 is NMe and X 2 is CH;

Y 1 is NMe, X 1 is N, Y 2 is NMe and X 2 is N;

Y 1 is O, X 1 is CH, Y 2 is NMe and X 2 is CH; or

Y 1 is O, X 1 is CH, Y 2 is NMe and X 2 is N; and

wherein in A4:

Z 1 is NMe, X 1 is CH and Y 1 is O; and

wherein in A5:

Z 1 is CH, X 1 is CH and Y 1 is NMe;

Z 1 is CH, X 1 is CH and Y 1 is O;

Z 1 is N, X 1 is CH and Y 1 is NMe; or

Z 1 is N, X 1 is CH and Y 1 is O.

19. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable carrier or diluent.

20. A method of treatment of a patient suffering from a bacterial infection, comprising administering to said patient a therapeutically acceptable amount of a compound according to claim 1 .