US 12,441,710 B2
Substituted piperidino compounds and related methods of treatment
Lewis D. Pennington, Arlington, MA (US); Younggi Choi, Stow, MA (US); Hoan Huynh, Waltham, MA (US); Brian M. Aquila, Marlborough, MA (US); Ingo Andreas Mugge, Waltham, MA (US); Yuan Hu, Waltham, MA (US); James R. Woods, Waltham, MA (US); Brian Kenneth Raymer, Holliston, MA (US); Jörg Martin Bentzien, White Plains, NY (US); Jonathan Ward Lehmann, Burlington, MA (US); Srinivasa Karra, Pembroke, MA (US); Roman A. Valiulin, Cambridge, MA (US); and Daljit Matharu, Lexington, MA (US)
Assigned to Alkermes, Inc., Waltham, MA (US)
Filed by Alkermes, Inc., Waltham, MA (US)
Filed on Aug. 4, 2023, as Appl. No. 18/230,329.
Application 18/230,329 is a continuation of application No. 17/556,295, filed on Dec. 20, 2021, granted, now 11,760,747.
Claims priority of provisional application 63/128,511, filed on Dec. 21, 2020.
Prior Publication US 2024/0076283 A1, Mar. 7, 2024
This patent is subject to a terminal disclaimer.
Int. Cl. C07D 401/14 (2006.01); A61P 25/26 (2006.01); C07D 211/98 (2006.01); C07D 401/04 (2006.01); C07D 471/04 (2006.01); C07D 487/04 (2006.01)
CPC C07D 401/14 (2013.01) [A61P 25/26 (2018.01); C07D 211/98 (2013.01); C07D 401/04 (2013.01); C07D 471/04 (2013.01); C07D 487/04 (2013.01)] 47 Claims
 
1. A compound of Formula I-A or a pharmaceutically acceptable salt thereof:

OG Complex Work Unit Chemistry
wherein:
T is CR6 or N;
U is CR5 or N;
V is CR4 or N;
W is CR3 or N;
X is CR2 or N;
and provided that

OG Complex Work Unit Chemistry
includes no more than 3 nitrogen atoms in the ring;
E is selected from the group consisting of NRaRb, C1-C3 alkylene-NRaRb, C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4- to 10-membered heterocyclyl, and C1-C3 alkylene-(4 to 10-membered heterocyclyl) wherein the C1-C3 alkylene-NRaRb, C1-C3 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C8 cycloalkyl, C1-C3 alkylene-(C3-C8 cycloalkyl), 4- to 10-membered heterocyclyl, or C1-C3 alkylene-(4 to 10-membered heterocyclyl) is unsubstituted or substituted with one or more halogen, hydroxyl, C1-C3 alkyl, or C1-C3 alkoxyl;
Ra and Rb are each, independently, H or unsubstituted C1-C3 alkyl;
R1 is (CRcRd)n-(C6-C10 aryl) or (CRcRd)n-(5 to 10-membered heteroaryl) wherein the aryl or heteroaryl is unsubstituted or substituted with one or more halogen, hydroxyl, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogen or deuterium;
Rc and Rd are each, independently, H, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogen or deuterium;
n is 0 or 1;
each of R2, R3, R4, R5, and R6, when present, is, independently, selected from the group consisting of H, halogen, deuterium, hydroxyl, cyano, unsubstituted C1-C3alkyl, and C1-C3alkyl substituted with one or more halogen or deuterium;
each of R7, R8, R9, R10, R11, R12, and R13 is, independently, H, halogen, unsubstituted C1-C3 alkyl, or C1-C3 alkyl substituted with one or more halogen or deuterium;
or, alternatively, R8 and R11, together form an unsubstituted C1-C3 alkylene or a C1-C3 alkylene substituted with one or more halogen;
or, alternatively, R9 and R10, together form an unsubstituted C1-C3 alkylene or a C1-C3 alkylene substituted with one or more halogen;
p is 0, 1, 2, 3, or 4; and
each R14 is, independently, selected from the group consisting of deuterium, halogen, hydroxyl, and cyano.