IP Library › Granted Patent US 12,428,404
Granted Patent B2
US 12,428,404 · App. 18/514,959 · Granted Sep 30, 2025

Inhibitors of LRRK2 kinase

Inventors: David James Bearss (Lehi, UT); John Sai Keong Kauwe, III (Lehi, UT); Alexis Henri Abel Mollard (Lehi, UT)
Assignee: Halia Therapeutics, Inc.
C07D403/14C07D239/47C07D401/14C07D403/12C07D405/14C07D413/12C07D413/14C07D491/107C07D498/08
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Quick Facts
Patent No.
US 12,428,404
App. No.
18/514,959
Granted
Sep 30, 2025
Kind
B2
Abstract

Compounds having activity as inhibitors of LRRK2 kinase are provided. The compounds have Structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein A, B, R 1a , R 1b , R 2 , and L are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of LRRK2 kinase are also provided.

Claims (30)

1. A compound having the following Structure (I):

or a pharmaceutically acceptable salt, or stereoisomer thereof, wherein:

A is phenylene or 5 or 6-membered heteroarylene;

B is C 3 -C 8 monocyclic cycloalkyl optionally substituted with one or more substituents selected from amino, halo, hydroxyl, oxo, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 hydroxylalkyl, C 1 -C 6 aminoalkyl, C 1 -C 6 alkylaminylalkyl, C 1 -C 6 alkoxy; C 1 -C 6 haloalkoxy, C 1 -C 6 alkylcarbonyl, C 1 -C 6 haloalkylcarbonyl, C 1 -C 6 alkylaminyl, C 1 -C 6 haloalkylaminyl, C 1 -C 6 alkylcarbonylaminyl, C 1 -C 6 haloalkylcarbonylaminyl, C 3 -C 8 cycloalkyl, C 3 -C 8 cycloalkylcarbonyl, C 3 -C 8 halocycloalkylaminyl, and C 3 -C 8 cycloalkylcarbonylaminyl;

L is a direct bond;

R 1a and R 1b are each independently H, halo, cyano, C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 1 -C 6 alkoxy or C 3 -C 8 cycloalkyl; and

R 2 is 3-8-membered heterocyclyl optionally substituted with one or more substituents selected from halo, cyano, C 1 -C 6 alkyl, hydroxyl, alkoxy, and C 1 -C 6 haloalkyl.

2. The compound of claim 1 , wherein A is phenylene.

3. The compound of claim 1 , wherein A is unsubstituted phenylene.

4. The compound of claim 1 , wherein A is a 5 or 6-membered heteroarylene.

5. The compound of claim 1 , wherein A is pyrazolylene.

6. The compound of claim 1 , wherein B is substituted.

7. The compound of claim 1 , wherein B has one of the following structures:

8. The compound of claim 1 , wherein B has one of the following structures:

9. The compound of claim 1 , wherein R 1a , R 1b , or both are selected from the group consisting of H, methyl, fluoro, chloro, cyano, methoxy, trifluoromethyl, and cyclopropyl.

10. The compound of claim 1 , wherein R 1b is H and R 1a is fluoro.

11. The compound of claim 1 , wherein R 2 is substituted.

12. The compound of claim 1 , wherein R 2 is substituted with one or more substituents selected from the group consisting of methyl, ethyl, iso-propyl, fluoro, trifluoromethyl, and cyano.

13. The compound of claim 1 , wherein R 2 is unsubstituted.

14. The compound of claim 1 , wherein

has one of the following structures:

15. The compound of claim 1 , wherein

has one of the following structures:

16. The compound of claim 1 , wherein the compound has one of the following structures:

17. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable carrier, diluent, or excipient.

18. 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 cancer, lung cancer, acute myelogenous leukemia, multiple myeloma leprosy, Crohn's disease, amyotrophic lateral sclerosis, rheumatoid arthritis, and ankylosing spondylitis, the method comprising administering a therapeutically effective amount of a compound of claim 1 , to a subject in need thereof.

19. The method of claim 18 , wherein the LRRK2-mediated disease or disorder is Parkinson's disease, or Lewy body dementia.

20. The method of claim 18 , wherein the LRRK2-mediated disease or disorder is Alzheimer's disease or L-DOPA induced dyskinesia.

21. The method of claim 18 , wherein the LRRK2-mediated disease or disorder is kidney cancer, breast cancer, prostate cancer, a blood cancer, papillary cancer, lung cancer, acute myelogenous leukemia, or multiple myeloma.

22. The method of claim 18 , wherein the LRRK2-mediated disease or disorder is leprosy, Crohn's disease, amyotrophic lateral sclerosis, rheumatoid arthritis, or ankylosing spondylitis.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 29, 2026
From: BEARSS, DAVID JAMES; KAUWE, JOHN SAI KEONG, III; MOLLARD, ALEXIS HENRI ABEL
To: HALIA THERAPEUTICS, INC.
Reel/Frame 075115/0905 →
Continuity (4)
Continuation 18065259 · Dec 13, 2022
Division 17702600 · Mar 23, 2022
Provisional Application 63164804 · Mar 23, 2021
Related Publication 20240190848A1 · Jun 13, 2024
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