Emopamil-binding protein inhibitors and uses thereof

The compound of any one of claims to 1 to 4, wherein the compound is represented by Formula (VII):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is O, CH2, or a bond;
• R1 is H and R2 is 4 to 6-membered monocyclic heterocyclyl or 6 to 10-membered bicyclic heterocyclyl;
• or R1 and R2 together with the N atom from which they are attached form a 4 to 7-membered monocyclic heterocycle or 6 to 10-membered bicyclic heterocycle;
• R3 is phenyl or 5 or 6-membered monocyclic heteroaryl, each of which is optionally substituted with one or two R5;
• each R5 is independently selected from C1-3alkyl, C1-3haloalkyl, C3-4 cycloalkyl, OR5a, cyano, and halo;
• R5a is C1-3haloalkyl.

A method of treating a disease mediated by Emopamil-Binding Protein, comprising administering to a subject an effective amount of a compound represented by Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is O, CH2, or a bond, provided when X is a bond, p and q are 1;
• p is 0 or 1, provided that when p is 0, q is 1;
• q is 0 or 1, provided that when q is 0, p is 1;
• R1 and R2 are each independently selected from H, C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, 6 to 10-membered bicyclic heterocycle, and 4 to 6-membered monocyclic heterocyclyl, wherein the C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, and 4 to 6-membered monocyclic heterocyclyl are each optionally substituted with one or more R4, provided at least one of R1 and R2 is not H;
• or R1 and R2 together with the N atom from which they are attached form a 4 to 7-membered monocyclic heterocycle or 6 to 10-membered bicyclic heterocycle, each of which is optionally substituted with one or more R4;
• each R4 is independently selected from OR4a, halo, C1-3alkyl, C3-8cycloalkyl, and 4 to 6-membered monocyclic heterocyclyl;
• R4a is selected from H and C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R3 is phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, or 6 to 10 membered bicyclic heterocycle, wherein the phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, and 6 to 10 membered bicyclic heterocycle are each optionally substituted with one or more substituent R5;
• each R5 is independently selected from C1-3alkyl, C3-6cycloalkyl, OR5a, cyano, halo, and 5 or 6-membered monocyclic heteroaryl, wherein the C1-3alkyl, C3-6 cycloalkyl, and heteroaryl are optionally substituted with one or more R5b;
• R5a is selected from H, C1-3alkyl, and C3-6cycloalkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R5b is selected from OR5a, C1-3alkyl, cyano, and halo;
• R6, for each occurrence, is independently halo or C1-3alkyl, or two R6 together to form a —C1-3alkylene;
• n is 0, 1, or 2;
• m is 0, 1, or 2.

A method of treating a disease mediated by Emopamil-Binding Protein, comprising administering to a subject an effective amount of a compound represented by Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is O, CH2, or a bond, provided when X is a bond, p and q are 1;
• p is 0 or 1, provided that when p is 0, q is 1;
• q is 0 or 1, provided that when q is 0, p is 1;
• R1 and R2 are each independently selected from H, C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, and 4 to 6-membered monocyclic heterocyclyl, wherein the C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, and 4 to 6-membered monocyclic heterocyclyl are each optionally substituted with one or more R4, provided at least one of R1 and R2 is not H;
• or R1 and R2 together with the N atom from which they are attached form a 4 to 7-membered monocyclic heterocycle or 6 to 10-membered bicyclic heterocycle, each of which is optionally substituted with one or more R4;
• R4 is selected from OR4a, halo, C1-3alkyl, or C3-8cycloalkyl;
• R4a is selected from H and C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R3 is phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, or 6 to 10 membered bicyclic heterocycle, wherein the phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, and 6 to 10 membered bicyclic heterocycle are each optionally substituted with one or more substituent R5;
• R5 is selected from C1-3alkyl, C3-6cycloalkyl, OR5a, cyano, halo, and 5 or 6-membered monocyclic heteroaryl, wherein the C1-3alkyl, C3-6cycloalkyl, and heteroaryl are optionally substituted with one or more R5b;
• R5a is selected from H, C1-3alkyl, and C3-6cycloalkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R5b is selected from OR5a, C1-3alkyl, cyano, and halo;
• R6, for each occurrence, is independently halo or C1-3alkyl, or two R6 together to form a —C1-3alkylene;
• n is 0, 1, or 2;
• m is 0, 1, or 2.

A method of treating an autoimmune disease in a subject comprising administering to the subject an effective amount of a compound represented by Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is O, CH2, or a bond, provided when X is a bond, p and q are 1;
• p is 0 or 1, provided that when p is 0, q is 1;
• q is 0 or 1, provided that when q is 0, p is 1;
• R1 and R2 are each independently selected from H, C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, 6 to 10-membered bicyclic heterocycle, and 4 to 6-membered monocyclic heterocyclyl, wherein the C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, and 4 to 6-membered monocyclic heterocyclyl are each optionally substituted with one or more R4, provided at least one of R1 and R2 is not H;
• or R1 and R2 together with the N atom from which they are attached form a 4 to 7-membered monocyclic heterocycle or 6 to 10-membered bicyclic heterocycle, each of which is optionally substituted with one or more R4;
• each R4 is independently selected from OR4a, halo, C1-3alkyl, C3-8cycloalkyl, and 4- to 6-membered heterocyclyl;
• R4a is selected from H and C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R3 is phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, or 6 to 10 membered bicyclic heterocycle, wherein the phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, and 6 to 10 membered bicyclic heterocycle are each optionally substituted with one or more substituent R5;
• each R5 is independently selected from C1-3alkyl, C3-6cycloalkyl, OR5a, cyano, halo, and 5 or 6-membered monocyclic heteroaryl, wherein the C1-3alkyl, C3-6 cycloalkyl, and heteroaryl are optionally substituted with one or more R5b;
• R5a is selected from H, C1-3alkyl, and C3-6cycloalkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R5b is selected from OR5a, C1-3alkyl, cyano, and halo;
• R6, for each occurrence, is independently halo or C1-3alkyl, or two R6 together to form a —C1-3alkylene;
• n is 0, 1, or 2;
• m is 0, 1, or 2.

A method of treating an autoimmune disease in a subject comprising administering to the subject an effective amount of a compound represented by Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is O, CH2, or a bond, provided when X is a bond, p and q are 1;
• p is 0 or 1, provided that when p is 0, q is 1;
• q is 0 or 1, provided that when q is 0, p is 1;
• R1 and R2 are each independently selected from H, C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, and 4 to 6-membered monocyclic heterocyclyl, wherein the C1-6alkyl, C3-8cycloalkyl, C3-8cycloalkenyl, and 4 to 6-membered monocyclic heterocyclyl are each optionally substituted with one or more R4, provided at least one of R1 and R2 is not H;
• or R1 and R2 together with the N atom from which they are attached form a 4 to 7-membered monocyclic heterocycle or 6 to 10-membered bicyclic heterocycle, each of which is optionally substituted with one or more R4;
• R4 is selected from OR4a, halo, C1-3alkyl, or C3-8cycloalkyl;
• R4a is selected from H and C1-3alkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R3 is phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, or 6 to 10 membered bicyclic heterocycle, wherein the phenyl, 5 or 6-membered monocyclic heteroaryl, 9 or 10-membered bicyclic heteroaryl, and 6 to 10 membered bicyclic heterocycle are each optionally substituted with one or more substituent R5;
• R5 is selected from C1-3alkyl, C3-6cycloalkyl, OR5a, cyano, halo, and 5 or 6-membered monocyclic heteroaryl, wherein the C1-3alkyl, C3-6cycloalkyl, and heteroaryl are optionally substituted with one or more R5b;
• R5a is selected from H, C1-3alkyl, and C3-6cycloalkyl, wherein the C1-3alkyl is optionally substituted with one or more halo;
• R5b is selected from OR5a, C1-3alkyl, cyano, and halo;
• R6, for each occurrence, is independently halo or C1-3alkyl, or two R6 together to form a —C1-3alkylene;
• n is 0, 1, or 2;
• m is 0, 1, or 2.