Inhibitors of rna helicase dhx9 and uses thereof

A method of treating a DHX9 mediated disease or disorder in a subject, comprising administering to the subject a compound represented by Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• X is H, C1-4alkyl, C2-4haloalkyl, or C(O)Rx;
• Rx is H, —OH, —OC1-4alkyl, or C1-4alkyl;
• Y is O or NRy;
• Ry is H or C1-4alkyl;
• R1 is C1-4alkyl or C3-6cycloalkyl;
• wherein the C1-4alkyl or C3-6cycloalkyl are each optionally and independently substituted with 1 to 3 halo;
• Ring A is a C3-6cycloalkyl, 4 to 6-membered monocyclic heterocyclyl, 6 to 10 membered bicyclic heterocyclyl, phenyl, 5 to 6-membered monocyclic heteroaryl, or 8 to 10-membered bicyclic heteroaryl;
• m is 0 to 3;
• each R2 is independently selected from C1-4alkyl, C3-6cycloalkyl, halo, OR2a, cyano, —NR2bR2c, —SO2R2a, —C(O)R2d, and —C(O)NR2bR2c, wherein the C1-4alkyl and C3-6cycloalkyl are optionally substituted with 1 to 4 R2e;
• or 2 R2 together form oxo;
• R2a is H, C1-4alkyl, C1-4haloalkyl, C1-4alkoxyC1-4alkyl, or benzyl;
• R2d is H, C1-4alkyl, C3-6cycloalkyl;
• OR2a, phenyl, 4 to 6-membered monocyclic heterocyclyl or 5 to 6-membered monocyclic heteroaryl, wherein the C1-4alkyl is optionally substituted with 1 to 3 halo;
• R2b and R2c are each independently selected from H, C1-4alkyl, C3-6cycloalkyl, phenyl, 4 to 6-membered monocyclic heterocyclyl and 5 to 6-membered monocyclic heteroaryl;
• or R2b and R2c, together with the nitrogen to which they are attached form a 4 to 6 membered monocyclic heterocyclyl or 6 to 10 membered bicyclic heterocyclyl;
• wherein the 4 to 6 membered monocyclic heterocyclyl or 6 to 10 membered bicyclic heterocyclyl are each optionally substituted with 1 to 3 R2d;
• each R2e is independently selected from halo, cyano, NR2bR2c, OR2a, phenyl, and 4 to 6 membered monocyclic heterocyclyl;
• Z is a bond, —CH2—, —O—, —O—C1-4alkylene-*, —C1-4alkylene-O—*, —C(O)—, —C(O)O—*, —OC(O)—*, —S(O)2—, —S(O)2N(Za)—*, —N(Za)S(O)2—*, —N(Za)—, —N(Za)—C1-4alkylene-*, —C1-4alkylene-N(Za)—*, —C(O)N(Za)—*, or —C(O)N(Za)—C1-3alkylene-*, wherein * indicates the attachment point to R3;
• Za is H or C1-4alkyl;
• provided when X is H and Z is a bond, ring A is phenyl, pyridinyl, thiophenyl, pyrrolyl, pyrazolyl, thiazolyl, imidazolyl, furanyl, or 1,4,5,6-tetrahydrocyclopenta[c]pyrazolyl;
• R3 is C3-6cycloalkyl, 7 to 10-membered bicyclic carbocyclyl, 4 to 6-membered monocyclic heterocyclyl, 6 to 10-membered bicyclic heterocyclyl, phenyl, 5 to 6-membered monocyclic heteroaryl, or 8 to 10-membered bicyclic heteroaryl, wherein the C3-6cycloalkyl, 7 to 10-membered bicyclic carbocyclyl, 4 to 6-membered monocyclic heterocyclyl, 6 to 10-membered bicyclic heterocyclyl, phenyl, 5 to 6-membered monocyclic heteroaryl, or 8 to 10-membered bicyclic heteroaryl are each optionally and independently substituted with 1 to 4 R4;
• each R4 is independently selected from C1-4alkyl, halo, OR4a, cyano, —NR4bR4c, —C(O)R4a, —C(O)OR4a, —C(O)NR4bR4c, —NR4bC(O)R4a—NR4bC(O)OR4a, —SR4a, —SO2R4a, —SO2NR4bR4c, —P(O)R4bR4c, phenyl, 5 to 6-membered monocyclic heteroaryl, 4 to 6-membered monocyclic heterocyclyl, and 6 to 10-membered bicyclic heterocyclyl, wherein the C1-4alkyl is optionally substituted with 1 to 4 R4d, and wherein the phenyl, 5 to 6-membered monocyclic heteroaryl, 4 to 6-membered monocyclic heterocyclyl and 6 to 10-membered bicyclic heterocyclyl are each optionally substituted with 1 to 3 R4e;
• or two R4 together form oxo;
• R4a is H, C1-4alkyl optionally substituted with 1 to 4 R4d, C3-6cycloalkyl, 4 to 6-membered monocyclic heterocyclyl, phenyl, or 5 to 6-membered monocyclic heteroaryl;
• wherein the C3-6cycloalkyl, 4 to 6-membered monocyclic heterocyclyl, phenyl or 5 to 6-membered monocyclic heteroaryl are each optionally and independently substituted with 1 to 3 R4e;
• R4b and R4c are each independently selected from H, phenyl, 4 to 6-membered monocyclic heterocyclyl, 5 to 6-membered monocyclic heteroaryl, and C1-4alkyl optionally substituted with 1 to 4 R4d;
• each R4d is independently selected from halo, OR4f, —C(O)C1-4alkyl, —C(O)NR4bR4c, —C(O)C1-4haloalkyl, phenyl, 4- to 6-membered monocyclic heterocyclyl, and 5 to 6-membered monocyclic heteroaryl, wherein the phenyl and 5 to 6-membered monocyclic heteroaryl are each optionally substituted with 1 to 3 R4g;
• each R4e is independently selected from halo, C1-4alkyl optionally substituted with 1 to 3 halo, cyano, OR4f, —NR4bR4c, —C(O)H, —C(O)C1-4alkyl, —C1-4alkylene-C(O)NR4bR4c, and —C(O)NR4bR4c;
• or two R4e together form oxo;
• R4f is H, C1-4alkyl, C1-4haloalkyl, phenyl or 5 to 6-membered monocyclic heteroaryl, wherein the phenyl and 5 to 6-membered monocyclic heteroaryl are each optionally substituted with one to three halo;
• each R4g is independently selected from halo, OR4f, C1-4alkyl, halo, cyano, —NR4bR4c, —C(O)H, and —C(O)OR4f.