Compounds for improving mRNA splicing

1. A compound of Formula (I):

or a pharmaceutically acceptable salt thereof, wherein:

L is selected from the group consisting of methylene, C 2-6 alkenylene, and C 2-6 alkynylene, wherein the C 2-6 alkenylene and C 2-6 alkynylene are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;

R 1 is selected from the group consisting of C 6-10 aryl, 2-benzofuranyl, 4-quinolinyl, and a 5-6 member heteroaryl, each optionally substituted by 1, 2, 3, or 4 independently selected R 1A groups;

each R 1A is independently selected from halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 haloalkyl, C 1-6 alkoxy, —C(═O)OH, —C(═O)C 1-6 alkyl, —C(═O)C 1-6 haloalkyl, and —C(═O)C 1-6 alkoxy;

R 2 is selected from the group consisting of H, oxo, azido, halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl OR a2 , C(═O)R b2 , C(═O)OR b2 , NR c2 R d2 , C(═O)NR c2 R d2 , —OC(═O)NR c2 R d2 , NR c2 C(═O)R b2 , NR c2 C(═O)OR b2 , NR c2 C(═O)NR c2 R d2 , NR c2 S(═O) 2 R b2 , NR c2 R d2 , S(O)NR c2 R d2 , and S(O) 2 NR c2 R d2 , wherein the C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;

R 3 is selected from the group consisting of H, oxo, azido, halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, OR a3 , SR a3 , C(═O)R b3 , C(═O)OR b3 , NR c3 R d3 , C(═O)NR c3 R d3 , OC(═O)NR c3 R d3 , NR c3 C(═O)R b3 , NR c3 C(═O)OR b3 , NR c3 C(═O)NR c3 R d3 , NR c3 S(═O) 2 R b3 , NR c3 S(═O) 2 NR c3 R d3 , S(O)NR c3 R d3 , and S(O) 2 NR c3 R d3 , wherein the C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;

R 4 is selected from the group consisting of H, oxo, azido, halo, CN, NO 2 , C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, OR a4 , C(═O)R b4 , C(═O)OR b4 , NR c4 R d4 , C(═O)NR c4 R d4 , —OC(═O)NR c4 R d4 , NR c4 C(═O)R b4 , NR c4 C(═O)OR b4 , NR c4 C(═O)NR c4 R d4 , NR c4 S(═O) 2 R b4 , NR c4 S(═O) 2 NR c4 R d4 , S(O)NR c4 R d4 , and S(O) 2 NR c4 R d4 , wherein the C 1-6 alkyl, C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;

R 5 is halo;

R 6 is selected from the group consisting of H, C 1-6 haloalkyl, C 1-6 hydroxyalkyl, and C 1-6 alkoxy;

each R a2 , R b2 , R c2 , R d2 , R a3 , R b3 , R c3 , R d3 , R a4 , R b4 , R c4 , and R d4 , is independently selected from the group consisting of H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 hydroxyalkyl, C 1-6 haloalkyl, C 1-6 alkoxy, —(C 1-6 alkylene)-C 1-6 alkoxy, C 3-10 cycloalkyl, —(C 1-6 alkylene)-C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, wherein the C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-10 cycloalkyl, —(C 1-6 alkylene)-C 3-10 cycloalkyl, C 6-10 aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;

or R c2 and R d2 together with the N atom to which they are connected, come together to form a 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl ring, each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;

or R c3 and R d3 together with the N atom to which they are connected, come together to form a 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl ring, each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups;

or R c4 and R d4 together with the N atom to which they are connected, come together to form a 5-10 membered heteroaryl or 4-10 membered heterocycloalkyl ring, each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups; and

each R 20 is independently selected from the group consisting of OH, SH, CN, NO 2 , halo, oxo, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 haloalkyl, C 1-4 cyanoalkyl, C 1-4 hydroxyalkyl, C 1-4 alkoxy, —(C 1-4 alkyl)-(C 1-4 alkoxy), —(C 1-4 alkoxy)-(C 1-4 alkoxy), C 1-4 haloalkoxy, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl, amino, C 1-4 alkylamino, di(C 1-4 alkyl)amino, carbamyl, C 1-4 alkylcarbamyl, di(C 1-4 alkyl)carbamyl, carbamoyl, C 1-4 alkylcarbamoyl, di(C 1-4 alkyl)carbamoyl, C 1-4 alkylcarbonyl, C 1-4 alkoxycarbonyl, C 1-4 alkylcarbonylamino, C 1-4 alkylsulfonylamino, aminosulfonyl, C 1-4 alkylaminosulfonyl, di(C 1-4 alkyl)aminosulfonyl, aminosulfonylamino, C 1-4 alkylaminosulfonylamino, di(C 1-4 alkyl)aminosulfonylamino, aminocarbonylamino, C 1-4 alkylaminocarbonylamino, and di(C 1-4 alkyl)aminocarbonylamino.

2. The compound of claim 1 , wherein L is methylene and R 1 is selected from the group consisting of:

3. The compound of claim 1 , wherein R 3 is selected from the group consisting of H, oxo, azido, CN, C 1-6 alkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl, 5-6 membered heterocycloalkyl, OR a3 , SR a3 , NR c3 R d3 , C(═O)OR a3 , —C(═O)NR c3 R d3 , —OC(═O)R b3 , wherein the C 1-6 alkyl, C 3-6 cycloalkyl, phenyl, 5-6 membered heteroaryl and 5-6 membered heterocycloalkyl are each optionally substituted by 1, 2, 3, or 4 independently selected R 20 groups; R 5 is halo; and, R 6 is hydrogen.

4. A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

5. The compound of claim 1 , wherein the compound is selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.