US 11,987,597 B2
Modulators of TNF-α activity
Toufike Kanouni, Palm Beach Gardens, FL (US)
Assigned to FORWARD THERAPEUTICS, INC., Palm Beach Gardens, FL (US)
Filed by Forward Therapeutics, Inc., Palm Beach Gardens, FL (US)
Filed on Sep. 21, 2023, as Appl. No. 18/471,977.
Application 18/471,977 is a continuation of application No. PCT/US2023/068223, filed on Jun. 9, 2023.
Claims priority of provisional application 63/351,116, filed on Jun. 10, 2022.
Prior Publication US 2024/0076306 A1, Mar. 7, 2024
Int. Cl. A61K 9/08 (2006.01); A61K 9/48 (2006.01); C07D 471/02 (2006.01); C07F 9/6558 (2006.01); C07F 9/6561 (2006.01); C07F 9/6584 (2006.01)
CPC C07F 9/6561 (2013.01) [A61K 9/08 (2013.01); A61K 9/4825 (2013.01); C07D 471/02 (2013.01); C07F 9/65583 (2013.01); C07F 9/6584 (2013.01)] 21 Claims
 
1. A compound, or pharmaceutically acceptable salt, solvate, or N-oxide thereof, wherein the compound has a structure of Formula (IB):

OG Complex Work Unit Chemistry
wherein:
A is N;
B is C—R;
R is selected from halogen, amino, or optionally substituted C1-C3 alkyl;
R1 is selected from halogen, cyano, optionally substituted C1-C3 alkyl, optionally substituted C3-C5 cycloalkyl, optionally substituted C2-C3 alkenyl, or optionally substituted C2-C3 alkynyl;
R2 is L-G; wherein L is a bond, —O—, —NH—, —NH (optionally substituted C1-C3 alkylene)-, optionally substituted C1-C3 alkylene, or optionally substituted cyclopropyl; and G is an optionally substituted C6 aryl, or optionally substituted 5- or 6-membered heteroaryl;
R3 is hydroxy or optionally substituted C1-C6 alkyl;
R4 is hydroxy or optionally substituted C1-C6 alkyl; or R3 and R4 join to form optionally substituted phosphorus-containing 3- to 8-membered heterocyclyl;
each R5 and R6 is independently selected from hydrogen, halogen, or optionally substituted C1-C3 alkyl;
W is N;
X is C—R8;
Y is C—R9;
Z is C—R10;
R8 is selected from hydrogen, halogen, —CN, optionally substituted C1-C3 alkyl, optionally substituted C1-C3 alkoxy, or —NH (optionally substituted C1-C3 alkyl); and
each R9 and R10 is independently selected from hydrogen, halogen, —CN, optionally substituted C1-C3 alkyl, optionally substituted C3-C7 cycloalkyl, optionally substituted C1-C3 alkoxy, or —NH (optionally substituted C1-C3 alkyl).