7-pyrrolyl tetracycline compounds and methods of use thereof

1. A compound of formula (I):

wherein:

A represents an aromatic, 5-membered heterocycle optionally substituted by one or more groups “R” selected from

halogen,

—NRaRb,

C 1-6 alkyl,

C 2-6 alkenyl,

C 3-6 alkynyl,

aryl,

heteroaryl,

hydroxy,

—OC 1-6 alkyl,

formyl,

cyano,

trifluoromethyl,

—CHNOR,

—CO 2 Ra,

—CONRaRb,

—NRaC(O)Ra,

—NRaC(O)ORa,

—OC(O)NRaRb,

—OC(O)Ra,

—OC(O)ORa,

or a C 1-6 alkyl group substituted by one or more groups selected from hydroxy,

—NRaRb,

—OC 1-6 alkyl,

—SRa,

—CHNOR,

—CO 2 Ra,

—CONRaRb,

—NRaC(O)Ra,

—NRaC(O)ORa,

—OC(O)NRaRb,

—OC(O)Ra,

—OC(O)ORa

Ra and Rb independently represent hydrogen or C 1-6 alkyl;

R 1 represents hydrogen, C 1-6 alkyl or together R 1 and R 3 represent a CH 2 moiety;

R 2 represents hydrogen, —OC 1-6 alkyl, —O(O)C 1-6 alkyl or hydroxy;

R 3 represents hydrogen, hydroxy or together R 3 and R 1 represent a CH 2 moiety, or a pharmaceutically acceptable salt or solvate thereof.

2. A pharmaceutical formulation comprising a compound of claim 1 and one or more pharmaceutically acceptable carriers.

3. A compound of claim 1 , wherein the compound is:

4. The compound of claim 1 , wherein A is tetrazole.

5. The compound of claim 4 , wherein R is hydrogen.

6. The compound of claim 1 , wherein A is triazole.

7. The compound of claim 6 , wherein said triazole is 1, 2, 3-triazole.

8. The compound of claim 7 , wherein R is CORa.

9. The compound of claim 8 , wherein Ra is C 1-6 alkyl.

10. The compound of claim 1 , wherein A is pyrrolyl.

11. The compound of claim 10 , wherein R is formyl.

12. The compound of claim 10 , wherein R is cyano.

13. The compound of claim 10 , wherein R is CHNORa.

14. The compound of claim 13 , wherein Ra is hydrogen.

15. The compound of claim 13 , wherein Ra is methyl.

16. The compound of claim 1 , wherein R 1 , R 2 , and R 3 are each hydrogen.

17. A compound selected from the group consisting of:

[4(R,S)-(4aα,5aα, 12aα)]-4-(Dimethylamino)-7-(1H-Tetrazol-1-yl)-1,4,4a,5,5a,6, 11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide;

[4-S-(4aα,5aα, 12aα)]-4-(Dimethylamino)-7-[(4-ethoxycarbonyl)-1H-triazol-1-yl]-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide;

[4-S-(4aα,5aα, 12aα)]-4-(Dimethylamino)-7-[(5-ethoxycarbonyl)-1H-triazol-1-yl 1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide;

[4S-(4aα,5aα, 12aα)]-4-(Dimethylamino)-7-(1H-pyrrol-1-yl-3-carboxaldehyde)-1,4,4a,5,5a,6,11,12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide;

[4S-(4aα,5aαα, 12aα)]-4-(Dimethylamino)-7-(3-((hydroxymino)-methyl)-1H-pyrrol-1-yl)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide;

[4S-(4aα,5aαα, 12aα)]-7-(3-Cyanopyrrol-1-yl)-4-(dimethylamino)-1,4,4a,5,5a,6,11,12a-octahydro-3, 10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide; and

[4S-(4aα,5aα, 12aα)]-4-(Dimethylamino)-7-(3-((methyloxymino)methyl)-1H-pyrrol-1-yl)-1,4,4a,5,5a,6,11, 12a-octahydro-3,10,12,12a-tetrahydroxy-1,11-dioxo-2-naphthacenecarboxamide.