US 11,053,218 B2
3-(1-oxoisoindolin-2-yl)piperidine-2,6-dione derivatives and uses thereof
Rohan Eric John Beckwith, Maynard, MA (US); Simone Bonazzi, Cambridge, MA (US); Artiom Cernijenko, Cambridge, MA (US); Aleem Fazal, Burlington, MA (US); Ritesh Bhanudasji Tichkule, Cambridge, MA (US); and Michael Scott Visser, Braintree, MA (US)
Filed by Novartis AG, Basel (CH)
Filed on Mar. 31, 2020, as Appl. No. 16/835,938.
Application 16/835,938 is a continuation of application No. 16/532,118, filed on Aug. 5, 2019, granted, now 10,647,701.
Application 16/532,118 is a continuation of application No. 16/532,106, filed on Aug. 5, 2019, granted, now 10,640,489.
Application 16/532,118 is a continuation of application No. 16/108,713, filed on Aug. 22, 2018, granted, now 10,414,755.
Application 16/532,106 is a continuation of application No. 16/108,713, filed on Aug. 22, 2018, granted, now 10,414,755.
Claims priority of provisional application 62/549,225, filed on Aug. 23, 2017.
Prior Publication US 2020/0231569 A1, Jul. 23, 2020
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/14 (2006.01); A61K 31/4412 (2006.01); C07D 401/04 (2006.01); C07D 407/14 (2006.01); C07D 409/14 (2006.01); C07D 413/14 (2006.01); C07D 417/14 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01); C07D 487/08 (2006.01); C07D 495/04 (2006.01); C07D 513/04 (2006.01); A61P 35/00 (2006.01)
CPC C07D 401/14 (2013.01) [A61P 35/00 (2018.01); C07D 401/04 (2013.01); C07D 407/14 (2013.01); C07D 409/14 (2013.01); C07D 413/14 (2013.01); C07D 417/14 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01); C07D 487/08 (2013.01); C07D 495/04 (2013.01); C07D 513/04 (2013.01)] 21 Claims
 
1. A compound of Formula (Ib):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, stereoisomer, or tautomer thereof,
wherein:
each R1 is independently (C1-C6)alkyl, (C1-C6)haloalkyl, (C1-C6)hydroxyalkyl, or halogen;
R2 is (C1-C6)alkyl, (C6-C10)aryl, 5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, or (C3-C8)cycloalkyl, wherein the alkyl is optionally substituted with one or more R4; and the aryl, heteroaryl, and cycloalkyl are optionally substituted with one or more R5;
each R4 is independently selected from —C(O)OR6, —C(O)NR6R6, —NR6C(O)R6′, (C6-C10)aryl, 5-or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, (C3-C5)cycloalkyl, and 5- to 7-membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from O, N, and S, wherein the aryl, heteroaryl, cycloalkyl, and heterocycloalkyl groups are optionally substituted with one or more R7;
each R5 is independently selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)hydroxy alkyl, halogen, —OH, —NH2, CN, (C3-C7)cycloalkyl, 5- to 7-membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from O, N, and S, (C6-C10)aryl, and 5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, or
two R5, when on adjacent atoms, together with the atoms to which they are attached form a (C6-C10)aryl ring or a 5- or 6-membered heteroaryl ring comprising 1 to 3 heteroatoms selected from 0, N, and S, optionally substituted with one or more R10, or
two R5, when on adjacent atoms, together with the atoms to which they are attached form a (C5-C7)cycloalkyl ring or a 5- to 7-membered heterocycloalkyl ring comprising 1 to 3 heteroatoms selected from O, N, and S optionally substituted with one or more R10;
R6 and R6′ are each independently H or (C1-C6)alkyl;
each R7 is independently selected from (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, —C(O)R8, —C(O)OR8, —C(O)NR8R9, —NR8C(O)R9, (C1-C6)hydroxyalkyl, halogen, —OH, —NH2, CN, (C6-C10)aryl, 5- or 6-membered heteroaryl comprising 1 to 3 heteroatoms selected from O, N, and S, (C3-C7)cycloalkyl, and 5- to 7-membered heterocycloalkyl comprising 1 to 3 heteroatoms selected from O, N, and S, or
two R7, when on adjacent atoms, together with the atoms to which they are attached form a (C6-C10)aryl ring or a 5- or 6-membered heteroaryl ring comprising 1 to 3 heteroatoms selected from O, N, and S, optionally substituted with one or more R10, or
two R7, when on adjacent atoms, together with the atoms to which they are attached form a (C5-C7)cycloalkyl ring or a 5- to 7-membered heterocycloalkyl ring comprising 1 to 3 heteroatoms selected from O, N, and S, optionally substituted with one or more R10;
R8 and R9 are each independently H or (C1-C6)alkyl;
each R10 is independently selected from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)hydroxyalkyl, halogen, —OH, —NH2, and CN;
n is 1 or 2; and
q is 0, 1, 2, 3, or 4.