Back to results
US 2025/0026753 A1Published application
Fused triazinone derivatives and methods of using the same
AssigneeRgenta Therapeutics, Inc.
InventorsTravis T. Wager, Zhiping Weng, Hualin Simon Xi
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to compounds of Formula (I) or (II) or subformulas thereof: (I) and do their prodrugs, pharmaceutically acceptable salts, pharmaceutical compositions, methods of use, and methods for their preparation. The compounds of the present disclosure may act as small molecule splicing modulator that modulate splicing of mRNA, such as pre-mRNA, encoded genes, and methods of use of the compounds for modulating splicing and treating related diseases and conditions. The compounds disclosed herein may possess activity toward various genetic pathways and are accordingly useful in methods of treatment of the human or animal body.
Claims42
A compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:
- A is saturated or partially unsaturated mono- or bi-cyclic 4- to 9-membered heterocycloalkyl or NR1R2, wherein the heterocycloalkyl comprises 1 or 2 nitrogen ring atoms and is optionally substituted with 1, 2, 3, or 4 R6;
- R1 is heterocycloalkyl comprising 1 nitrogen ring atom, optionally substituted with 1, 2, 3, or 4 R6;
- R2 is hydrogen, C1-7alkyl, or C3-8cycloalkyl;
- R3 is H, halo, C1-7alkyl, OR5, N(R5)2, C3-8cycloalkyl, or heterocycloalkyl;
- R4 is aryl or bicyclic 9-membered heteroaryl comprising 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein R4 is optionally substituted with 1, 2, or 3 R7;
- each R5 is independently C1-7alkyl, C3-8cycloalkyl, or heterocycloalkyl;
- each R6 is independently selected from the group consisting of halogen, hydroxy, cyano, —COOH, —C(O)—C1-C6alkyl, —C(O)O—C1-C6alkyl, C1-C7alkyl, C1-C8heteroalkyl, C1-7alkoxy-heterocycloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C6alkoxy, —(CH2)0-2-C3-C8cycloalkyl, 4-7-membered monocyclic heterocycloalkyl, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, —NHC(O)—C1-C6alkyl, —N(C1-C6alkyl)-C(O)—C1-C6alkyl, —C(O)—NH2, —C(O)—NH(C1-C6alkyl), and —C(O)—N(C1-C6alkyl)2, wherein the alkyl, alkenyl, alkynyl, and alkoxy are optionally substituted with one or more halogen, hydroxyl or NH2, and wherein the cycloalkyl and heterocycloalkyl are optionally substituted with one or more halogen, hydroxyl, C1-C6alkyl, C1-C6heteroalkyl, C1-C6alkoxy, or NH2;
- or
- two R6 on the same carbon can be taken together as keto (═O);
- or
- two R6 together form C1-7alkylene;
- each R7 is independently halo, cyano, C1-7alkyl, C1-7haloalkyl, C1-7alkoxy, C1-7 haloalkoxy, or C3-8cycloalkyl, wherein the C1-7alkyl is optionally substituted with OH;
- R16 is H, halo, C1-7alkyl, OR5, N(R5)2, C3-8cycloalkyl, or heterocycloalkyl;
- and. R17 is H, halo, C1-7alkyl, OR5, N(R5)2, C3-8cycloalkyl, or heterocycloalkyl.
12 more elements
A compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:
- A is saturated or partially unsaturated mono- or bi-cyclic 4- to 9-membered heterocycloalkyl or NR1R2, wherein the heterocycloalkyl comprises 1 or 2 nitrogen ring atoms and is optionally substituted with 1, 2, 3, or 4 R6;
- R1 is heterocycloalkyl comprising 1 nitrogen ring atom, optionally substituted with 1, 2, 3, or 4 R6;
- R2 is hydrogen, C1-7alkyl, or C3-8cycloalkyl;
- R3 is H, halo, C1-7alkyl, OR5, N(R5)2, C3-8cycloalkyl, or heterocycloalkyl;
- R4 is aryl or bicyclic 9-membered heteroaryl comprising 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein R4 is optionally substituted with 1, 2, or 3 R7;
- each R5 is independently C1-7alkyl, C3-8cycloalkyl, or heterocycloalkyl;
- each R6 is independently C1-7alkyl, amino, amino-C1-7alkyl, C3-8cycloalkyl, heterocycloalkyl, or C1-7alkoxy-heterocycloalkyl, or two R6 together form C1-7alkylene;
- each R7 is independently halo, cyano, C1-7alkyl, C1-7haloalkyl, C1-7alkoxy, C1-7 haloalkoxy, or C3-8cycloalkyl, wherein the C1-7alkyl is optionally substituted with OH;
- R16 is H, halo, C1-7alkyl, or OR5;
- and.
- R17 is H, halo, C1-7alkyl, or OR5.
9 more elements
A compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:
- A is a nitrogen-containing heterocycloalkyl, wherein the nitrogen-containing heterocycloalkyl comprises 1 or 2 nitrogen ring atoms and is optionally substituted with 1, 2, 3, or 4 R6;
- R3 is H, C1-7alkyl, OR5, N(R5)2, C3-8cycloalkyl, or heterocycloalkyl;
- R4 is a bicyclic 9-membered heteroaryl comprising 2, 3, or 4 heteroatoms independently selected from N and O, wherein R4 can be optionally substituted with 1, 2, or 3 R7;
- each R5 is independently H, C1-7alkyl, C3-8cycloalkyl, or heterocycloalkyl;
- each R6 is independently C1-7alkyl, amino, amino-C1-7alkyl, C3-8cycloalkyl, heterocycloalkyl, and C1-7alkoxy-heterocycloalkyl, or two R6 together form C1-7alkylene;
- each R7 is independently halo, C1-7alkyl, C1-7haloalkyl, C1-7alkoxy, or C1-7haloalkoxy;
- R16 is H, halo, C1-7alkyl, or OR5;
- and.
- R17 is H, halo, C1-7alkyl, or OR5.
7 more elements
A compound of Formula (II):
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:
- A is saturated or partially unsaturated mono- or bi-cyclic 4- to 9-membered heterocycloalkyl or NR1R2, wherein the heterocycloalkyl comprises 1 or 2 nitrogen ring atoms and is optionally substituted with 1, 2, 3, or 4 R6;
- R1 is heterocycloalkyl comprising 1 nitrogen ring atom, optionally substituted with 1, 2, 3, or 4 R6;
- R2 is hydrogen, C1-7alkyl, or C3-8cycloalkyl;
- R3 is H, halo, C1-7alkyl, OR5, N(R5)2, C3-8cycloalkyl, or heterocycloalkyl;
- R4 is aryl or bicyclic 9-membered heteroaryl comprising 2, 3, or 4 heteroatoms independently selected from N, O, and S, wherein R4 is optionally substituted with 1, 2, or 3 R7;
- each R5 is independently C1-7alkyl, C3-8cycloalkyl, or heterocycloalkyl;
- each R6 is independently C1-7alkyl, amino, amino-C1-7alkyl, C3-8cycloalkyl, heterocycloalkyl, or C1-7alkoxy-heterocycloalkyl, or two R6 together form C1-7alkylene;
- and
- each R7 is independently halo, cyano, C1-7alkyl, C1-7haloalkyl, C1-7alkoxy, C1-7 haloalkoxy, or C3-8cycloalkyl, wherein the C1-7alkyl is optionally substituted with OH.
7 more elements
A compound of Formula (II):
- or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein:
- A is nitrogen-containing heterocycloalkyl, wherein the nitrogen-containing heterocycloalkyl comprises 1 or 2 nitrogen ring atoms and is optionally substituted with 1, 2, 3, or 4 R6;
- R3 is H, C1-7alkyl, OR5, N(R5)2, C3-8cycloalkyl, or heterocycloalkyl;
- R4 is a bicyclic 9-membered heteroaryl comprising 2, 3, or 4 heteroatoms independently selected from N and O, wherein R4 can be optionally substituted with 1, 2, or 3 R7;
- each R5 is independently C1-7alkyl, C3-8cycloalkyl, or heterocycloalkyl;
- each R6 is independently C1-7alkyl, amino, amino-C1-7alkyl, C3-8cycloalkyl, heterocycloalkyl, and C1-7alkoxy-heterocycloalkyl, or two R6 together form C1-7alkylene;
- and
- each R7 is independently halo or C1-7alkyl.
5 more elements
Dependencies are inferred from the claim text.