Tetracycline compounds

1. A compound of Structural Formula I:

or a pharmaceutically acceptable salt thereof, wherein:

X is —CF 3 ;

Y is selected from —NH—C(O)—(CH 2 ) 1-4 —N(R 2 )(R 3 ), —N(H)—C(O)-heterocyclyl, —N(H)—C(O)-carbocyclyl, NH—S(O) 2 —(C 1 -C 6 ) alkyl, wherein:

each R 2 is independently selected from hydrogen, and (C 1 -C 3 )alkyl;

each R 3 is independently selected from hydrogen, (C 1 -C 6 )alkyl, —(C 0 -C 6 ) alkylene-carbocyclyl, —(C 0 -C 6 )alkylene-heterocyclyl;

or R 2 and R 3 , taken together with the nitrogen atom to which they are bound form a heterocyclyl, wherein the heterocyclyl optionally comprises 1 to 4 additional heteroatoms independently selected from N and S;

wherein:

each carbocyclyl is independently a 3-12 membered saturated or unsaturated aliphatic ring or a 6-12 membered aromatic ring;

each heterocyclyl is independently a 4-12 membered saturated or unsaturated aliphatic ring containing 1, 2, 3, 4 or 5 heteroatoms independently selected from N, O or S or a 5-12 membered heteroaryl containing 1, 2, 3 or 4 heteroatoms independently selected from N, O, and S;

each carbocyclyl or heterocyclyl is optionally and independently substituted with one or more substituents independently selected from chloro, fluoro, (C 1 -C 4 )alkyl, —OH, —O—(C 1 -C 4 )alkyl, fluoro-substituted-(C 1 -C 4 )alkyl, —C(O)—(C 1 -C 4 )alkyl, —C(O)-(fluoro-substituted-(C 1 -C 4 )alkyl, and —N(R G )(R G );

each alkyl is optionally and independently substituted with one or more substituents independently selected from fluoro, chloro, —O—(C 1 -C 4 )alkyl, and fluoro-substituted-(C 1 -C 4 )alkyl; and

each R G is hydrogen or (C 1 -C 4 )alkyl, wherein each alkyl in the group represented by R G is optionally and independently substituted with one or more substituents independently selected from —(C 1 -C 4 )alkyl, (C 3 -C 6 )cycloalkyl, halo, —OH, —O—(C 1 -C 4 )alkyl, and —(C 1 -C 4 )alkylene-O—(C 1 -C 4 )alkyl.

2. The compound of claim 1 , wherein:

Y is selected from —NH—C(O)—CH 2 —N(R 2 )(R 3 ),

—NH—C(O)-phenyl, —NH—C(O)-thienyl and —NH—S(O) 2 —(C 1 -C 6 )alkyl, wherein:

each R 2 is independently selected from hydrogen, and (C 1 -C 2 )alkyl; and

each R 3 is independently selected from hydrogen, (C 1 -C 6 )alkyl, and —(C 0 -C 1 )alkylene-cycloalkyl; or

R 2 and R 3 taken together with the nitrogen atom to which they are bound form a saturated heterocyclyl;

ring A represents a 4-7 membered saturated heterocyclyl;

R 3′ is hydrogen or methyl;

each cycloalkyl, phenyl or heterocyclyl is optionally and independently substituted with one or more substituents independently selected from fluoro, (C 1 -C 4 )alkyl, —O—(C 1 -C 4 )alkyl, fluoro-substituted-(C 1 -C 4 )alkyl, and —N(R 2 )(R 2 ); and

each alkyl is optionally and independently substituted with one or more substituents independently selected from fluoro, —O—(C 1 -C 4 )alkyl, and fluoro-substituted-(C 1 -C 4 )alkyl.

3. The compound of claim 1 , wherein:

Y is selected from —NH—C(O)—CH 2 —N(R 2 )(R 3 ), and

each R 2 is independently selected from hydrogen and —CH 3 ;

each R 3 is independently selected from (C 1 -C 6 )alkyl and —(C 0 -C 1 )alkylene-carbocyclyl, wherein the (C 1 -C 6 )alkyl is optionally substituted with fluoro or —OCH 3 ; or

R 2 and R 3 , taken together with the nitrogen atom to which they are bound form a saturated heterocyclyl optionally substituted with fluoro or —OCH 3 ; and

ring A represents a 4-7 membered saturated heterocyclyl;

R 3′ is hydrogen or methyl;

each carbocyclyl or heterocyclyl is optionally and independently substituted with one or more substituents independently selected from fluoro, (C 1 -C 4 )alkyl, —O—(C 1 -C 4 )alkyl, fluoro-substituted-(C 1 -C 4 )alkyl, and —N(R G )(R G ); and

each alkyl is optionally and independently substituted with one or more substituents independently selected from fluoro, —O—(C 1 -C 4 )alkyl, and fluoro-substituted-(C 1 -C 4 )alkyl.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

Y is

5. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier or diluent and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

6. A method for treating a bacterial infection or colonization in a subject, comprising administering to the subject an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

7. The method of claim 6 , wherein the infection is caused by a Gram-positive bacteria.

8. The method of claim 7 , wherein the Gram-positive bacteria is selected from the group consisting of Staphylococcus spp., Streptococcus spp., Propionibacterium spp., Enterococcus spp., Bacillus spp., Corynebacterium spp., Nocardia spp., Clostridium spp., Actinobacteria spp., and Listeria spp.

9. The method of claim 6 , wherein the infection is caused by a Gram-negative bacteria.

10. The method of claim 9 , wherein the Gram-negative bacteria is selected form the group consisting of Enterobactericeae, Bacteroidaceae, Vibrionaceae, Pasteurellae, Pseudomonadaceae, Neisseriaceae, Rickettsiae, Moraxellaceae any species of Proteeae, Acinetobacter spp., Helicobacter spp., and Campylobacter spp.

11. The method of claim 6 , wherein the infection is caused by a bacteria selected from the group consisting of rickettsiae, chlamydiae, Legionella spp. and Mycoplasma spp.

12. The method of claim 6 , wherein the infection is caused by more than one bacteria.

13. The method of claim 6 , wherein the infection is caused by a bacteria resistant to one or more antibiotics.

14. The method of claim 13 , wherein the infection is caused by a bacteria resistant to tetracycline.

15. The method of claim 13 , wherein the infection is caused by a bacteria resistant to methicillin.

16. The method of claim 13 , wherein the infection is caused by a bacteria resistant to vancomycin.

17. The method of claim 13 wherein the infection is caused by a bacteria resistant to a quinolone or fluoroquinolone.

18. The method of claim 13 wherein the infection is caused by a bacteria resistant to tigecycline.