US 11,773,085 B2
Methods and compounds for treating disorders
Qianhe Zhou, Winchester, MA (US); Michael Bocker, Cambridge, MA (US); David Simon Millan, Stow, MA (US); Ho Man Chan, Carlisle, MA (US); Luis Soares, Cambridge, MA (US); Matthew Russell Netherton, Cambridge, MA (US); Sabine K. Ruppel, Cambridge, MA (US); Zhaoxia Yang, Belmont, MA (US); Jason T. Lowe, East Bridgewater, MA (US); and Francois Brucelle, Belmont, MA (US)
Assigned to Foghorn Therapeutics Inc., Cambridge, MA (US)
Filed by Foghorn Therapeutics Inc., Cambridge, MA (US)
Filed on Jul. 29, 2020, as Appl. No. 16/942,021.
Application 16/942,021 is a continuation of application No. PCT/US2019/015733, filed on Jan. 29, 2019.
Claims priority of provisional application 62/688,309, filed on Jun. 21, 2018.
Claims priority of provisional application 62/653,285, filed on Apr. 5, 2018.
Claims priority of provisional application 62/623,845, filed on Jan. 30, 2018.
Prior Publication US 2021/0009568 A1, Jan. 14, 2021
Int. Cl. A61P 35/00 (2006.01); A61K 31/551 (2006.01); C07D 519/00 (2006.01); C07D 403/14 (2006.01); A61K 9/16 (2006.01); A61K 45/06 (2006.01)
CPC C07D 403/14 (2013.01) [A61K 9/1605 (2013.01); A61K 45/06 (2013.01); A61P 35/00 (2018.01)] 4 Claims
 
1. A method of treating synovial sarcoma in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound having the structure of Formula I:
A-L-B   Formula I
wherein
L is a linker;
B is a degradation moiety, which has the structure of Formula A-1:

OG Complex Work Unit Chemistry
wherein
Y1 is

OG Complex Work Unit Chemistry
each of R3 and R4 is, independently, H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;
q is 0, 1, 2, 3, or 4; and
each R2 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxyl, —SH, or optionally substituted amino;
A has the structure of Formula E-a:

OG Complex Work Unit Chemistry
where
R22 is H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl;
R23 is H, halogen, optionally substituted C1-C6 alkyl, or optionally substituted C6-C10 aryl;
s′ is 0, 1, or 2;
each R24 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxyl, —SH, or optionally substituted amino, or two R24 combine with the carbon atoms to which they are attached to form an optionally substituted C6-C10 aryl or optionally substituted C2-C9 heteroaryl;
s is 0, 1, 2, 3, or 4; and
each R25 is, independently, halogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heterocyclyl, optionally substituted C6-C10 aryl, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C6 alkenyl, optionally substituted C2-C6 heteroalkenyl, hydroxyl, —SH, or optionally substituted amino, or a pharmaceutically acceptable salt thereof.