US 11,964,971 B2
Methods and compositions for modulating splicing
Michael Luzzio, Noank, CT (US); Brian Lucas, Arlington, MA (US); Tiansheng Wang, Concord, MA (US); and Jun Feng, Acton, MA (US)
Assigned to SKYHAWK THERAPEUTICS, INC., Waltham, MA (US)
Filed by Skyhawk Therapeutics, Inc., Waltham, MA (US)
Filed on Jul. 29, 2021, as Appl. No. 17/388,100.
Application 17/388,100 is a continuation of application No. PCT/US2020/016897, filed on Feb. 6, 2020.
Claims priority of provisional application 62/802,057, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,075, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,059, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,071, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,072, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,065, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,068, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,054, filed on Feb. 6, 2019.
Claims priority of provisional application 62/802,061, filed on Feb. 6, 2019.
Prior Publication US 2023/0068499 A1, Mar. 2, 2023
Int. Cl. C07D 451/14 (2006.01); C07D 451/06 (2006.01); C07D 498/08 (2006.01); C07D 519/00 (2006.01)
CPC C07D 451/14 (2013.01) [C07D 451/06 (2013.01); C07D 498/08 (2013.01); C07D 519/00 (2013.01)] 20 Claims
 
1. A compound of Formula (III), or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof:

OG Complex Work Unit Chemistry
wherein,
E is —NR—, —O—, —S—, —S(═O)—, —S(═O)2-, or —S(═O)(=NRE)-;
RE is hydrogen, substituted or unsubstituted C1-C3 alkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C2-C5 heterocycloalkyl, substituted or unsubstituted C2-C3 alkenyl, or substituted or unsubstituted C2-C3 alkynyl;
each RA is independently hydrogen, deuterium, F, Cl, —CN, —OR1, —SR1, —S(═O)R1, —S(═O)2R1, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C4 cycloalkyl, or substituted or unsubstituted C2-C3 heterocycloalkyl;
ring Q is substituted or unsubstituted aryl or substituted or unsubstituted heteroaryl;
custom character is a single bond or a double bond;
X is

OG Complex Work Unit Chemistry
and Z is C; or
X is —O—, —S—, —NR3—,

OG Complex Work Unit Chemistry
and Z is CR2;
W is substituted or unsubstituted C1-C3 alkylene, substituted or unsubstituted C2-C3 alkenylene, substituted or unsubstituted C1-C2 heteroalkylene, substituted or unsubstituted C3-C8 cycloalkylene, or substituted or unsubstituted C2-C7 heterocycloalkylene;
R is hydrogen, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, substituted or unsubstituted C1-C4 heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, or substituted or unsubstituted C2-C5 heterocycloalkyl;
each R1 is independently hydrogen, deuterium, substituted or unsubstituted C1-C4 alkyl, -CD3, substituted or unsubstituted C1-C4 haloalkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted C2-C5 heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R2 is hydrogen, deuterium, substituted or unsubstituted C1-C4 alkyl, -CD3, or substituted or unsubstituted haloalkyl;
R3 is hydrogen, —CN, substituted or unsubstituted C1-C4 alkyl, —CD3, substituted or unsubstituted haloalkyl, substituted or unsubstituted C1-C4 heteroalkyl, —C1-C4 alkylene-OR1, substituted or unsubstituted C3-C4 cycloalkyl, or substituted or unsubstituted C2-C3 heterocycloalkyl;
each R4 is independently hydrogen, deuterium, substituted or unsubstituted C1-C4 alkyl, -CD3, substituted or unsubstituted C1-C4 haloalkyl, or substituted or unsubstituted heteroalkyl;
each R11, R12, R13, R14, R16, and R17 is independently selected from the group consisting of hydrogen, deuterium, F, —OR1, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, and substituted or unsubstituted heteroalkyl;
R15 and R18 are:
1) the same and selected from the group consisting of hydrogen and deuterium;
2) the same and selected from the group consisting of F, —OR1, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 fluoroalkyl, and substituted or unsubstituted C1-C4 heteroalkyl; or
3) not the same and selected from the group consisting of hydrogen, deuterium, F, —OR1, substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted fluoroalkyl, and substituted or unsubstituted C1-C4 heteroalkyl;
a is 0 or 1;
b is 0;
c is 1; and
d is 0 or 1.