US 12,384,776 B2
Compounds and uses thereof
Sabine K. Ruppel, Cambridge, MA (US); Zhaoxia Yang, Belmont, MA (US); Jason T. Lowe, East Bridgewater, MA (US); Johannes H. Voigt, Cambridge, MA (US); Matthew Netherton, Cambridge, MA (US); Francois Brucelle, Belmont, MA (US); and Rishi G. Vaswani, Lexington, MA (US)
Assigned to FOGHORN THERAPEUTICS INC., Cambridge, MA (US)
Appl. No. 17/425,250
Filed by Foghorn Therapeutics Inc., Cambridge, MA (US)
PCT Filed Jan. 29, 2020, PCT No. PCT/US2020/015744
§ 371(c)(1), (2) Date Jul. 22, 2021,
PCT Pub. No. WO2020/160196, PCT Pub. Date Aug. 6, 2020.
Claims priority of provisional application 62/881,114, filed on Jul. 31, 2019.
Claims priority of provisional application 62/798,384, filed on Jan. 29, 2019.
Prior Publication US 2022/0098190 A1, Mar. 31, 2022
Int. Cl. C07D 471/04 (2006.01); C07D 401/14 (2006.01); C07D 471/10 (2006.01); C07D 491/048 (2006.01); C07D 519/00 (2006.01)
CPC C07D 471/04 (2013.01) [C07D 401/14 (2013.01); C07D 471/10 (2013.01); C07D 491/048 (2013.01); C07D 519/00 (2013.01)] 17 Claims
 
1. A compound having the structure of Formula I:

OG Complex Work Unit Chemistry
wherein
R1 is H, optionally substituted C1-C6 alkyl, optionally substituted C2-C6 alkenyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted C3-C10 carbocyclyl;
Z1 is CR2 or N;
R2 is H, 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, or optionally substituted C2-C9 heteroaryl;

OG Complex Work Unit Chemistry
X1 is a bond, O, NR3a,

OG Complex Work Unit Chemistry
 or CR4aR5a;
X2 is O, NR3b,

OG Complex Work Unit Chemistry
 or CR4bR5b;
X3 is O, NR3c,

OG Complex Work Unit Chemistry
 or CR4cR5c;
X4 is a bond, O, NR3d,

OG Complex Work Unit Chemistry
 or CR4dR5d;
X5 is O or NR3e and X6 is CR4fR5f, or X5 is CR4eR5e and X6 is O or NR3f;
X7 is O, NR3g, or CR4gR5g;
X8 is O, NR3h, or CR4hR5h;
each of R3a, R3b, R3c, and R3d is, independently, H, halogen, hydroxyl, 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, optionally substituted C1-C6 acyl, thiol, optionally substituted sulfone, optionally substituted sulfonamide, or optionally substituted amino, or R3a and R4b, R4a and R3b, R4b and R4a, R3b and R4c, R4b and R4c, R3c and R4b, R3c and R4d, R4c and R4d, and/or R3d and R4c, together with the atoms to which each is attached, combine to form optionally substituted C2-C9 heterocyclyl;
each of R4a, R4b, R4c, and R4d is, independently, H, halogen, hydroxyl, 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, optionally substituted C1-C6 acyl, thiol, optionally substituted sulfone, or optionally substituted amino, or R3a and R4b, R4a and R3b, R4b and R4a, R3b and R4c, R4b and R4c, R3c and R4b, R3c and R4d, R4c and R4d, and/or R3d and R4c, together with the atoms to which each is attached, combine to form optionally substituted C2-C9 heterocyclyl;
each of R5a, R5b, R5c, and R5d is, independently, H, halogen, hydroxyl, 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, thiol, or optionally substituted amino;
each of R3e, R3f, R3g, and R3h is, independently, H, halogen, hydroxyl, 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, optionally substituted C1-C6 acyl, thiol, optionally substituted sulfone, optionally substituted sulfonamide, or optionally substituted amino, or R3e and R4f or R4e and R3f, together with the atoms to which each is attached, combine to form optionally substituted heterocyclycl;
each of R4e, R4f, R4g, and R4h is, independently, H, halogen, hydroxyl, 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, optionally substituted C1-C6 acyl, thiol, optionally substituted sulfone, optionally substituted sulfonamide, or optionally substituted amino, or R3e and R4f or R4e and R3f, together with the atoms to which each is attached, combine to form optionally substituted heterocyclycl;
each of R5e, R5f, R5g, and R5h is, independently, H, halogen, hydroxyl, 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, thiol, or optionally substituted amino; and
G is optionally substituted C6-C10 aryl, optionally substituted C3-C10 carbocyclyl, optionally substituted C2-C9 heteroaryl, or C2-C9 heterocyclyl,
or a pharmaceutically acceptable salt thereof.