INHIBITORS OF LRRK2 KINASE
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.
1 - 55 . (canceled)
56 . A compound having one of the following structures:
or a pharmaceutically acceptable salt or stereoisomer thereof.
57 . The compound of claim 56 , wherein the compound has the following structure:
58 . The compound of claim 56 , wherein the compound has the following structure:
59 . The compound of claim 56 , wherein the compound has the following structure:
60 . The compound of claim 56 , wherein the compound has the following structure:
61 . The compound of claim 56 , wherein the compound has the following structure:
62 . The compound of claim 56 , wherein the compound has the following structure:
63 . The compound of claim 56 , wherein the compound has the following structure:
64 . The compound of claim 56 , wherein the compound has the following structure:
65 . The compound of claim 56 , wherein the compound has the following structure:
66 . The compound of claim 56 , wherein the compound has the following structure:
67 . The compound of claim 56 , wherein the compound has the following structure:
68 . The compound of claim 56 , wherein the compound has the following structure:
69 . A pharmaceutical composition comprising a compound of claim 56 , and a pharmaceutically acceptable carrier, diluent or excipient.
70 . A method of treating a LRRK2-mediated disease or disorder, comprising administering a therapeutically effective amount of a compound of claim 56 , to a subject in need thereof.
71 . The method of claim 70 , wherein the disease or disorder is selected from neurodegenerative diseases, central nervous system (CNS) disorders, cancer, inflammatory diseases, and combinations thereof.
72 . The method of claim 71 , wherein the neurodegenerative disease is Parkinson's disease, or Lewy body dementia.
73 . The method of claim 71 , wherein the CNS disease is Alzheimer's disease or L-DOPA induced dyskinesia.
74 . The method of claim 71 , wherein the cancer is kidney cancer, breast cancer, prostate cancer, a blood cancer, papillary cancer, lung cancer, acute myelogenous leukemia, or multiple myeloma.
75 . The method of claim 71 , wherein the inflammatory disease is leprosy, Crohn's disease, amyotrophic lateral sclerosis, rheumatoid arthritis, or ankylosing spondylitis.