Bicyclic pyridone lactams and methods of use thereof

A compound of formula I:

• or a pharmaceutically acceptable salt thereof, wherein
• R1 is selected from the group consisting of H, C1-C4 alkyl and C1-C4 haloalkyl;
• the A ring is tetrazolyl or a 5 or 6 membered heteroaryl having 1 to 3 heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur;
• wherein the A ring is optionally substituted with 1 to 2 substituents selected from the group consisting of halogen, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 haloalkyl, C1-C4 alkoxy, C1-C4 haloalkoxy and cyano;
• and wherein if a nitrogen atom in the A ring is substituted, the substituent is not halogen, cyano, or a C1-C6 alkoxy, C1-C6 haloalkoxy or C1-C6 thioalkyl having an oxygen or sulfur atom directly bonded to the nitrogen atom;
• the B ring is selected from the group consisting of phenyl, 5 or 6 membered heteroaryl, 3 to 7 membered cycloalkyl, and 4 to 7 membered heterocyclyl;
• wherein the B ring is optionally substituted with:
• (a) 1 to 4 substituents selected from the group consisting of halogen, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 cycloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C1-C6 thioalkyl, cyano, phenyl, benzyl, CH2-(C3-C6 cycloalkyl), and CH2CH2-(C3-C6 cycloalkyl);
• wherein if a nitrogen atom in the C ring is substituted, the substituent is not halogen, cyano, or a C1-C6 alkoxy, C1-C6 haloalkoxy or C1-C6 thioalkyl having an oxygen or sulfur atom directly bonded to the nitrogen atom;
• (b) 1 to 2 substituents selected from the group consisting of C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, CH2-(4 to 6 membered heterocyclyl), CH2CH2-(4 to 6 membered heterocyclyl), and unsubstituted 5 or 6 membered heteroaryl;
• or
• (c) two adjacent substituents which together form phenyl, 5 or 6 membered heteroaryl, 4 to 6 membered heterocyclyl or C4-C6 cycloalkyl;
• L is selected from the group consisting of a bond, O, S, NH, NCH3, (CH2)m, CH(CH3), C(CH3)2, CF2, CH2O, CH2S, CH(OH), CH2NH, and CH2N(CH3), or L is absent such that the A ring and the B ring are fused;
• X is selected from the group consisting of O, S, SO, SO2, CH2, C(CH3)2, CF2 and CHCF3;
• each of Z1 to Z4 is independently selected from the group consisting of CR2, NR3 and C═O;
• Z5 is C or N;
• wherein only one of Z1 to Z4 is C═O;
• and:
• (i) if Z1 is C═O and Z5 is N, then Z2, Z3, Z4 are each CR2 and X is CH2;
• (ii) if Z1 is C═O and Z2 is N, then Z3 and Z4 are each CR2 and Z5 is C;
• (iii) if Z2 is C═O and Z1 is NR3, then Z3 and Z4 are each CR2 and Z5 is C;
• (iv) if Z2 is C═O and Z3 is NR3, then Z1 and Z4 are each CR2 and Z5 is C;
• (v) if Z3 is C═O and Z2 is NR3, then Z1 and Z4 are each CR2 and Z5 is C;
• (vi) if Z3 is C═O and Z4 is NR3, then Z1 and Z2 are each CR2 and Z5 is C;
• (vii) if Z4 is C═O and Z3 is NR3, then Z1 and Z2 are each CR2 and Z5 is C;
• n is 1 or 2;
• R2 is selected from the group consisting of H, F, C1-C6 alkyl, C1-C6 alkoxy, and C1-C6 haloalkyl;
• R3 is selected from the group consisting of H, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C3-C6 cycloalkyl, -C(R4)2-C3-C6 cycloalkyl, 4 to 6 membered heterocyclyl, and -C(R4)2-(4 to 6 membered heterocyclyl);
• and
• each R4 is independently selected from the group consisting of H, F, C1-C6 alkyl, C1C6 alkoxy, and C1-C6 haloalkyl;
• provided that if the B ring is tetrazolyl, L is selected from the group consisting of CH2, CH(CH3), C(CH3)2, CF2;
• and the C ring is phenyl.