US 12,103,919 B2
3-(5-oxy)-1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
Simone Bonazzi, Cambridge, MA (US); Artiom Cernijenko, Cambridge, MA (US); Jennifer Stroka Cobb, Stow, MA (US); Janetta Dewhurst, Framingham, MA (US); John Ryan Kerrigan, Wakefield, MA (US); Gary O'Brien, Maynard, MA (US); MooJe Sung, Belmont, MA (US); Noel Marie-France Thomsen, Chelmsford, MA (US); and Pamela Ting, Somerville, MA (US)
Assigned to NOVARTIS AG, Basel (CH)
Filed by NOVARTIS AG, Basel (CH)
Filed on Jun. 1, 2022, as Appl. No. 17/829,933.
Claims priority of provisional application 63/196,422, filed on Jun. 3, 2021.
Prior Publication US 2023/0019617 A1, Jan. 19, 2023
Int. Cl. C07D 401/14 (2006.01); A61K 31/4545 (2006.01); A61K 31/55 (2006.01); A61K 45/06 (2006.01); C07D 405/14 (2006.01)
CPC C07D 401/14 (2013.01) [A61K 31/4545 (2013.01); A61K 31/55 (2013.01); A61K 45/06 (2013.01); C07D 405/14 (2013.01)] 27 Claims
 
1. A compound of formula (I′) or a pharmaceutically acceptable salt, hydrate, solvate, stereoisomer, or tautomer thereof, wherein:

OG Complex Work Unit Chemistry
each R1 is independently selected from hydrogen, C1-C6alkyl, hydroxyl, halo, C1-C6haloalkyl, C1-C6haloalkoxyl, and C1-C6alkoxyl; or 2 R1 on the same carbon atom together with the same carbon atom to which they are attached form a C3-C8cycloalkyl; or 2 R1 on adjacent carbon atoms together with the adjacent carbon atoms to which they are attached form a C3-C8cycloalkyl; or 2 R1 on non-adjacent carbon atoms together with the non-adjacent carbon atoms to which they are attached form a bridging ring;
R2 is selected from hydrogen, C3-C11cycloalkyl, 4- to 11-membered heterocyclyl comprising 1-2 heteroatoms independently selected from N, O, and S, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C1-C10alkyl, —SO2R6, —C(═O)—R2a, —C(═O)—O—R2a, and —C(═O)NR2bR2c,
wherein the C3-C11cycloalkyl, 4- to 11-membered heterocyclyl, C2-C6alkynyl, and C1-C10alkyl are each independently substituted with 0-5 occurrences of R3;
R2a is selected from C1-C6alkyl, and 4- to 6-membered heterocyclyl comprising 1-2 heteroatoms independently selected from N, O, and S;
R2b and R2c are each independently selected from hydrogen, and C1-C6alkyl;
each R3 is independently selected from C1-C6alkoxyl, halo, C6-C10aryl, 5- to 10-membered heteroaryl comprising 1-4 heteroatoms independently selected from N, O, and S, 4- to 11-membered heterocyclyl comprising 1-2 heteroatoms independently selected from N, O, and S, and C3-C8cycloalkyl, wherein the C6-C10aryl, 5- to 10-membered heteroaryl, 4- to 11-membered heterocyclyl, and C3-C8cycloalkyl are each independently substituted with 0-4 occurrences of R4;
each R4 is independently selected from C1-C10alkyl, C1-C6alkoxyl, halo, and C3-C8cycloalkyl, wherein the C3-C8cycloalkyl is substituted with 0-3 occurrences of R5;
each R5 is independently selected from —CN, C1-C6alkyl, C1-C6alkoxyl, hydroxyl, and C1-C6haloalkyl;
R6 is selected from C3-C8cycloalkyl, C1-C6alkyl, a 4- to 6-membered heterocyclyl comprising 1-2 heteroatoms independently selected from N, O and S, and C6-C10aryl;
n is 0, 1, 2, 3, 4, or 5; and
m is 0, 1 or 2;
with the proviso that the compound of formula (I′) does not include 3-(1-oxo-5-(pyrrolidin-3-yloxy)isoindolin-2-yl)piperidine-2,6-dione.