Bicyclic heteroaryl kinase inhibitors and methods of use

摘要

Provided are compounds having an inhibitory effect on kinases including Mixed Lineage Kinases. Also provided are pharmaceutical compositions, methods of preparing the compounds, synthetic intermediates, and methods of using the compounds, independently or in combination with other therapeutic agents, for treating diseases and conditions that are affected by Mixed Lineage Kinase inhibition. Also provided are methods of treatment of neuropsychiatric disorders that comprise the inhibition of Mixed Lineage Kinases.

主权项

1. A compound of structural Formula VI or a salt thereof, wherein: Y3 is chosen from a bond, lower alkyl, lower carboxyl, and lower heteroalkyl; Y4 is chosen from O, S, C(O), SO, SO2, NH, N(CH3), CH2, CHF, CF2, CH(CH3), C(CH3)2, CH2O—, and —CH2N—; and R2 is chosen from phenyl and 6-membered monocyclic heteroaryl, either of which is optionally substituted with one or more substituents chosen from deuterium, halogen, hydroxy, lower amino, lower amido, C1-C3 alkoxy, and C1-C3 alkyl; R3 is chosen from cycloalkyl, aryl, heteroaryl, bicyclic heteroaryl, any of which is optionally substituted with one or more substituents chosen from deuterium, halogen, hydroxy, lower amino, lower amido, lower carboxyl, C1-C3 alkoxy, C1-C3 alkyl, (O), (S), cyano, haloalkyl, phenyl, cycloalkyl, heteroaryl, and cycloheteroalkyl; R14 is chosen from lower heteroalkyl, lower heterocycloalkyl, and lower heteroaryl, any of which is optionally substituted with one or more substituents chosen from deuterium, halogen, hydroxy, lower amino, lower amido, lower carboxyl, C1-C3 alkoxy, C1-C3 alkyl, (O), (S), haloalkyl, phenyl, benzyl, and lower cycloalkyl.