Tetracycline Compounds

A compound having Structural Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is C(R2), wherein R2 is —(C0-C6 alkylene)-heterocyclyl, wherein the heterocyclyl is optionally substituted on a nitrogen atom with —(C1-C6 alkyl);
• —(C0-C6 alkylene)-carbocyclyl;
• or —(C1-C6)alkyl substituted with NRBRB′;
• R1 is selected from hydrogen, fluoro, chloro, CF3 and OCF3;
• each of R3, R5 and R6 is independently selected from hydrogen, halo, —(C1-C6 alkyl), —ORA, —C(O)NRBRB′, NRBRB′, S(O)0-2RC, —(C0-C6 alkylene)-carbocyclyl, and —(C0-C6 alkylene)-heterocyclyl;
• or
• R4 is selected from hydrogen, methyl, ethyl, or propyl;
• R4′ is selected from hydrogen, ethyl, propyl, —S(O)2CH3, cyclopropyl, —C(O)CH3, or —C(O)CH2N(CH3)2;
• R6′ is selected from hydrogen, —(C1-C6 alkyl) and —(C3-C6 cycloalkyl);
• each RA is independently selected from hydrogen, —(C1-C6 alkyl), —(C0-C6 alkylene)-carbocyclyl, —(C0-C6 alkylene)-heterocyclyl, —C(O)—(C1-C6 alkyl), —C(O)—(C0-C6 alkylene)-carbocyclyl, —C(O)—(C0-C6 alkylene)-heterocyclyl, and —C(O)N(RD)(RE);
• each RB and each RB′ is independently selected from hydrogen, —(C1-C6 alkyl), —(C1-C6 haloalkyl), —(C0-C6 alkylene)-carbocyclyl, —(C0-C6 alkylene)-heterocyclyl, —S(O)1-2—(C1-C6 alkyl), —S(O)1-2—(C0-C6 alkylene)-carbocyclyl, —S(O)1-2—(C0-C6 alkylene)-heterocyclyl, —C(O)—(C1-C6 alkyl), —C(O)—(C0-C6 alkylene)-carbocyclyl, —C(O)H, —C(O)—(C0-C6 alkylene)-heterocyclyl, and —C(O)—(C0-C6 alkylene)-N(RD)(RE);
• each RC is independently selected from —(C1-C6 alkyl), —(C0-C6 alkylene)-carbocyclyl and —(C0-C6 alkylene)-heterocyclyl;
• and
• each RD and each RE is independently selected from hydrogen, —(C1-C6 alkyl), —(C0-C6 alkylene)-carbocyclyl, and —(C0-C6 alkylene)-heterocyclyl,
• wherein:
• any alkyl, or alkylene portion of R2, R3, R4, R4′, R5, R6 is optionally and independently substituted with one or more substituents independently selected from halo, ═O, ORA, NRBRB′, and S(O)0-2RC;
• any alkyl or alkylene portion of R6′, RA, or RC, is optionally and independently substituted with one or more fluoro;
• any carbocyclyl or heterocyclyl portion of any of R2, R3, R5, R6 is optionally and independently substituted on a carbon atom with one or more substituents independently selected from halo, ═O, C1-C4 fluoroalkyl, C1-C4 alkyl, —(C0-C6 alkylene)-(C3-C10 carbocyclyl), —(C0-C6 alkylene)-(4-13 membered heterocyclyl), ORA, —(C0-C6 alkylene)-NRBRB′, and S(O)0-2RC;
• any heterocyclyl portion of any of R2, R3, R5, R6 is optionally and independently substituted on a substitutable nitrogen atom with RF;
• each RF is independently selected from —(C1-C6 alkyl), —(C1-C6 haloalkyl), —(C1-C6 hydroxyalkyl), —(C0-C6 alkylene)-carbocyclyl, —(C0-C6 alkylene)-heterocyclyl, —S(O)1-2—(C1-C6 alkyl), —S(O)1-2—(C0-C6 alkylene)-carbocyclyl, —S(O)1-2—(C0-C6 alkylene)-heterocyclyl, —C(O)—(C1-C6 alkyl), —C(O)—(C0-C6 alkylene)-carbocyclyl, —C(O)H, —C(O)—(C0-C6 alkylene)-heterocyclyl, —(C0-C6 alkylene)-C(O)2—(C1-C6 alkyl), —(C1-C6 alkylene)-NRBRB′ and —C(O)N(RD)(RE);
• any carbocyclyl or heterocyclyl portion of RA, RB, RB′, RC, RD, RE, RF, any cycloalkyl portion of R6′, or any substituent of R2, R3, R5, R6 is optionally and independently substituted on a carbon atom with a one or more substituents independently selected from fluoro, chloro, C1-C4 alkyl, C1-C4 fluoroalkyl, —O—C1-C4 alkyl, —O—C1-C4 fluoroalkyl, ═O, —OH, —NH2, —NH(C1-C4 alkyl), and —N(C1-C4 alkyl)2;
• any heterocyclyl portion of RA, RB, RB′, RC, RD, RE, RF, or any heterocyclyl substituent of R2, R3, R5, or R6 is optionally substituted on a substitutable nitrogen atom with —C1-C4 alkyl, or —S(O)1-2—(C1-C4 alkyl).