Inhibitors of nlrp3 inflammasome

A compound of Formula III:

• or a pharmaceutically acceptable salt thereof;
• wherein
• is an optional double bond;
• X is CH, N, NH, or N(C1-6 alkyl);
• Y and Z are each independently selected from the group consisting of NH, NR9, O, S, N, CH, and CR9;
• Ring A is selected from the group consisting of C6-10 aryl, 5-6 membered heteroaryl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl;
• Ring B is selected from the group consisting of phenyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, and 3-6 membered heterocycloalkyl;
• alternatively, Ring B is absent and m is 0;
• R1 is selected from the group consisting of H, C1-6 alkyl, and C3-6 cycloalkyl, wherein alkyl and cycloalkyl are each optionally substituted with R6;
• R2 and R3 are each independently selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, and 3-6 membered heterocycloalkyl;
• alternatively, R2 and R3, together with the atom to which they are attached, form a ring selected from the group consisting of C3-7 cycloalkyl and 3-7 membered heterocycloalkyl;
• each R4 is independently selected from the group consisting of C1-6 alkyl, halo, OH, OR6, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NHCOR6, CN, C1-6 haloalkyl, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, and COR6;
• alternatively, two R4, together with the atoms to which they are attached, form a ring selected from the group consisting of phenyl, 5-6 membered heteroaryl, C4-6 cycloalkyl, and 4-6 membered heterocycloalkyl all of which are optionally substituted with one, two, or three R7;
• each R5 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, halo, OH, OR6, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NHCOR6, CN, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, COR6, and SO2R6;
• alternatively, two R5, together with the atoms to which they are attached, form a ring selected from the group consisting of phenyl, 5-6 membered heteroaryl, C4-6 cycloalkyl, and 4-6 membered heterocycloalkyl all of which are optionally substituted with one, two, or three R7;
• each R6 is independently selected from the group consisting of C1-6 alkyl, C0-6 alkyl-C6-10 aryl, C0-6 alkyl-5-10 membered heteroaryl, OC1-6 alkyl, C3-6 cycloalkyl, halo, NH2, NH(C1-6 alkyl), and N(C1-6 alkyl)2;
• each R7 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, halo, OH, OC1-6 alkyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, CN, COR8, and SO2R8;
• each R8 is independently selected from the group consisting of C1-6 alkyl, OC1-6 alkyl, halo, NH2, NH(C1-6 alkyl), and N(C1-6 alkyl)2;
• each R9 is independently selected from the group consisting of C1-6 alkyl, OC1-6 alkyl, halo, CN, OH, NH2, NH(C1-6 alkyl), and N(C1-6 alkyl)2;
• m is 0, 1, 2, or 3;
• n is 1, 2, or 3;
• and
• p is 0, 1, 2, or 3.

A method of treating a disease or disorder of the inner ear in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of Formula VII:

• or a pharmaceutically acceptable salt thereof, wherein
• X, Y, and Z, together with the ring to which they are attached, form
• Ring A is selected from the group consisting of C6-10 aryl, 5-10 membered heteroaryl, C3-10 cycloalkyl, and 4-10 membered heterocycloalkyl;
• Ring B is selected from the group consisting of phenyl, 5-6 membered heteroaryl, C3-6 cycloalkyl, and 3-6 membered heterocycloalkyl;
• alternatively, Ring B is absent and m is 0;
• Ring D is phenyl or pyridine;
• R1 is selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, OC1-6 alkyl, OC3-6 cycloalkyl, O(C0-6 alkyl-C6-10 aryl), C0-6 alkyl-C6-10 aryl, and OH, wherein alkyl, aryl, and cycloalkyl are each optionally substituted with R6;
• R2 and R3 are each independently selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, and 3-6 membered heterocycloalkyl;
• alternatively, R2 and R3, together with the atom to which they are attached, form a ring selected from the group consisting of C3-7 cycloalkyl and 3-7 membered heterocycloalkyl;
• each R4 is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, halo, OH, OR6, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, C1-6 alkyl-NHCOR6, NHCOR6, CN, C1-6 haloalkyl, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, and COR6;
• alternatively, two R4, together with the atoms to which they are attached, form a ring selected from the group consisting of phenyl, 5-6 membered heteroaryl, C4-6 cycloalkyl, and 4-6 membered heterocycloalkyl all of which are optionally substituted with one, two, or three R7;
• each R5 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, halo, OH, OR6, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, NHCOR6, CN, C3-7 cycloalkyl, 3-7 membered heterocycloalkyl, COR6, and SO2R6;
• alternatively, two R5, together with the atoms to which they are attached, form a ring selected from the group consisting of phenyl, 5-6 membered heteroaryl, C4-6 cycloalkyl, and 4-6 membered heterocycloalkyl all of which are optionally substituted with one, two, or three R7;
• each R6 is independently selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C0-6 alkyl-C6-10 aryl, C0-6 alkyl-5-10 membered heteroaryl, OC1-6 alkyl, C3-6 cycloalkyl, 3-6 membered heterocycloalkyl, halo, NH2, NH(C1-6 alkyl), and N(C1-6 alkyl)2;
• each R7 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, halo, OH, OC1-6 alkyl, NH2, NH(C1-6 alkyl), N(C1-6 alkyl)2, CN, COR8, and SO2R8;
• each R8 is independently selected from the group consisting of C1-6 alkyl, OC1-6 alkyl, halo, NH2, NH(C1-6 alkyl), and N(C1-6 alkyl)2;
• each R9 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 alkyl-OH, OC1-6 alkyl, C1-6 alkyl-O—C1-6 alkyl, O(C3-6 cycloalkyl), halo, CN, OH, NH2, NH(C1-6 alkyl), and N(C1-6 alkyl)2;
• m is 0, 1, 2, or 3;
• n is 0, 1, 2, or 3;
• and
• p is 0, 1, 2, or 3.