US 11,866,423 B2
Inhibitors of LRRK2 kinase
David James Bearss, Salt Lake City, UT (US); John Sai Keong Kauwe, III, Salt Lake City, UT (US); and Alexis Henri Abel Mollard, Lehi, UT (US)
Assigned to HALIA THERAPEUTICS, INC., Lehi, UT (US)
Filed by Halia Therapeutics, Inc., Lehi, UT (US)
Filed on Dec. 13, 2022, as Appl. No. 18/065,259.
Application 18/065,259 is a division of application No. 17/702,600, filed on Mar. 23, 2022, granted, now 11,578,061.
Claims priority of provisional application 63/164,804, filed on Mar. 23, 2021.
Prior Publication US 2023/0183217 A1, Jun. 15, 2023
Int. Cl. C07D 403/14 (2006.01); C07D 239/47 (2006.01); C07D 401/14 (2006.01); C07D 403/12 (2006.01); C07D 405/14 (2006.01); C07D 413/12 (2006.01); C07D 413/14 (2006.01); C07D 491/107 (2006.01); C07D 498/08 (2006.01)
CPC C07D 403/14 (2013.01) [C07D 239/47 (2013.01); C07D 401/14 (2013.01); C07D 403/12 (2013.01); C07D 405/14 (2013.01); C07D 413/12 (2013.01); C07D 413/14 (2013.01); C07D 491/107 (2013.01); C07D 498/08 (2013.01)] 26 Claims
 
1. A method of treating a LRRK2-mediated disease or disorder selected from the group consisting of Parkinson's disease, Lewy body dementia, Alzheimer's disease, L-DOPA induced dyskinesia, kidney cancer, breast cancer, prostate cancer, a blood cancer, papillary renal and thyroid carcinomas, lung cancer, acute myelogenous leukemia, leprosy, Crohn's disease, amyotrophic lateral sclerosis, rheumatoid arthritis, and ankylosing spondylitis, comprising administering a therapeutically effective amount of a compound having the following Structure (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt, or stereoisomer thereof, wherein:
A is phenylene or 5 or 6-membered heteroarylene, each of which is optionally substituted with one or more substituents selected from halo, C1-C6 alkyl, C3-C8 cycloalkyl, and C1-C6 alkoxy;
B is C3-C8 monocyclic cycloalkyl, C6-C10 spirocyclic cycloalkyl, C6-C10 fused-multicyclic cycloalkyl, C6-C10 bridged-multicyclic cycloalkyl, 3-8-membered monocyclic heterocyclyl, 3-8-membered monocyclic heterocyclylalkyl, 6-10-membered spirocyclic heterocyclyl, 6-10-membered fused-multicyclic heterocyclyl or 6-10-membered bridged-multicyclic heterocyclyl, each of which is optionally substituted with one or more substituents selected from amino, halo, hydroxyl, oxo, cyano, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 hydroxylalkyl, C1-C6 aminoalkyl, C1-C6 alkylaminylalkyl, C1-C6 alkoxy; C1-C6 haloalkoxy, C1-C6 alkylcarbonyl, C1-C6 haloalkylcarbonyl, C1-C6 alkylaminyl, C1-C6 haloalkylaminyl, C1-C6 alkylcarbonylaminyl, C1-C6 haloalkylcarbonylaminyl, C3-C8 cycloalkyl, C3-C8 cycloalkylcarbonyl, C3-C8 halocycloalkylaminyl, and C3-C8 cycloalkylcarbonylaminyl;
L is a direct bond, CH2 or C═O;
R1a and R1b are each independently H, halo, cyano, unsubstituted C1-C6 alkyl, unsubstituted C1-C6 haloalkyl, unsubstituted C1-C6 alkoxy or unsubstituted C3-C8 cycloalkyl; and
R2 is C1-C6 alkyl, C3-C8 cycloalkyl, 3-8-membered heterocyclyl, 6-10-membered spirocyclic heterocyclyl, 6-10-membered fused-multicyclic heterocyclyl or 6-10-membered bridged-multicyclic heterocyclyl each of which is optionally substituted with one or more substituents selected from halo, cyano, C1-C6 alkyl, hydroxyl, alkoxy, and C1-C6 haloalkyl, to a mammal in need thereof.