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US 2024/0190879 A1Published application
Fused bicyclic compounds useful for modulating nucleic acid splicing
AssigneeRemix Therapeutics Inc.
InventorsDominic Reynolds, Michael W. Seiler, Anant A. Agrawal, Frederic Vaillancourt, Peter Smith
Life of this patent
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Abstract
The present disclosure features compounds and related compositions that, inter alia, modulate nucleic acid splicing, e.g., splicing of a pre-mRNA, as well as methods of use thereof.
Claims37
A compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, or stereoisomer thereof, wherein:
- A and B are each independently cycloalkyl, heterocyclyl, aryl, or heteroaryl, each of which is optionally substituted with one or more R1;
- W is N, C, or C(R3a);
- X, Y, and Z are each independently C(R3a), C(R3a)(R3b), N, N(R3c), or O, wherein the bonds in the ring comprising W, X, Y, and Z may be single or double bonds as valency permits;
- M is C(R2) or N;
- L1 and L2 are each independently is absent, C1-C6-alkylene, C1-C6-heteroalkylene, —O—, —C(O)—, —N(R4)—, —N(R4)C(O)—, or —C(O)N(R4)—, wherein each alkylene and heteroalkylene is optionally substituted with one or more R5;
- each R1 is independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, C1-C6 alkylene-aryl, C1-C6 alkenylene-aryl, C1-C6 alkylene-heteroaryl, heteroaryl, halo, cyano, oxo, —ORA, —NRBRC, —NRBRC(O)RD, —NO2, —C(O)NRBRC, —C(O)RD, —C(O)ORD, —SRE, or —S(O)RD, wherein each alkyl, alkylene, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more R6;
- or
- two R1 groups, together with the atoms to which they are attached, form a 3-7-membered cycloalkyl, heterocyclyl, aryl, or heteroaryl, wherein each cycloalkyl, heterocyclyl, aryl, and heteroaryl are optionally substituted with one or more R6;
- each R2 is independently hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, or —ORA;
- R3a and R3b are each independently hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, halo, cyano, —ORA, —NRBRC, —C(O)RD, or —C(O)ORD;
- or
- each of R3a and R3b, together with the carbon atom to which they are attached, form an oxo group;
- R3c is hydrogen or C1-C6-alkyl;
- each R4 is independently hydrogen, C1-C6-alkyl, or C1-C6-haloalkyl;
- each R5 is independently hydrogen, C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, halo, cyano, oxo, —ORA, —NRBRC, —C(O)RD, or —C(O)ORD;
- each R6 is independently C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkynyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, —ORA, —NRBRC, —NRBC(O)RD, —NO2, —C(O)NRBRC, —C(O)RD, —C(O)ORD, —SRE, or —S(O)RD, wherein each alkyl, alkenyl, alkynyl, heteroalkyl, haloalkyl, cycloalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with one or more Ru;
- each RA is independently hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, aryl, heteroaryl, C1-C6 alkylene-aryl, C1-C6 alkylene-heteroaryl, —C(O)RD, or S(O)xRD;
- each of RB and RC is independently hydrogen, C1-C6 alkyl, C1-C6 heteroalkyl, cycloalkyl, heterocyclyl, or —ORA;
- or
- RB and RC together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with one or more R7;
- each RD and RE is independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 heteroalkyl, C1-C6 haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, C1-C6 alkylene-aryl, or C1-C6 alkylene-heteroaryl;
- each R7 is C1-C6-alkyl, halo, cyano, oxo, or —ORA1;
- each R1 is independently C1-C6-alkyl, C1-C6-heteroalkyl, C1-C6-haloalkyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, halo, cyano, oxo, or —ORA;
- each RA1 is hydrogen or C1-C6-alkyl;
- m is 0, 1, or 2;
- and
- x is 0, 1, or 2.
25 more elements
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13-21. (canceled)
33-34. (canceled)
(canceled)
41-42. (canceled)
47-48. (canceled)
Dependencies are inferred from the claim text.