Aryl ether-base kinase inhibitors

摘要

The present disclosure is generally directed to compounds which can inhibit AAK1 (adaptor associated kinase 1), compositions comprising such compounds, and methods for inhibiting AAK1.

主权项

1. A method of inhibiting adaptor associated kinase 1 (AAK1) activity, comprising contacting AAK1 with a compound of formula (I),or a pharmaceutically acceptable salt thereof, wherein:
R1 and R2 are independently selected from hydrogen, C3-C6cycloalkyl, and C1-C3alkyl wherein the C1-C3alkyl is optionally substituted with one, two, or three groups independently selected from C1-C3alkoxy, C1-C3alkylamino, amino, cyano, C1-C3dialkylamino, halo, and hydroxy; or R1 and R2 together are oxo; or R1 and R2, together with the carbon atom to which they are attached, form an oxetane ring; R3 is C1-C3alkyl-Y or C2-C8alkyl, wherein the C2-C8alkyl is optionally substituted with one, two, three, or four groups independently selected from C1-C3alkoxy, C1-C3alkylamino, C1-C3alkoxyC2-C3alkylamino, amino, aryl, halo, C1-C3haloalkylamino, C1-C3haloalkylcarbonylamino, hydroxy, —NRxRy, and C3-C8cycloalkyl, wherein the cycloalkyl is further optionally substituted with one, two, or three groups independently selected from C1-C3alkoxy, C1-C3alkyl, C1-C3alkylamino, C1-C3alkoxyC2-C3alkylamino, amino, aryl, arylC1-C3alkyl, halo, C1-C3haloalkyl, C1-C3haloalkylamino and hydroxy; R4 is selected from hydrogen, C1-C3alkoxy, C1-C3alkoxycarbonylamino, C1-C3alkyl, C1-C3alkylamino, C1-C3alkylcarbonylamino, amino, arylamino, arylcarbonylamino, C3-C6cycloalkylamino, C3-C6cycloalkylcarbonylamino, C3-C6cycloalkyloxy, halo, C1-C3haloalkoxy, C2-C3haloalkylamino, C2-C3haloalkylcarbonylamino, and hydroxy; R5 is selected from hydrogen, C1-C3alkyl, cyano, C3cycloalkyl, and halo; R6 is selected from hydrogen, C1-C3alkyl, C1-C3alkylcarbonylamino, amino, R7 is selected from hydrogen, C1-C3alkoxy, C1-C3alkyl, cyano, —CH2OH, —CH2OCH3, CH(CH3)OH, C(CH3)2OH, halo, and C1-C3haloalkyl; R8 is selected from hydrogen, C1-C3alkoxy, cyano, and halo; Rx and Ry, together with the nitrogen atom to which they are attached, form a three- to six-membered ring; and Y is selected from wherein R9 is selected from hydrogen, C1-C6alkyl, C3-C6cycloalkyl, and C1-C6alkylcarbonyl; n is 0, 1, 2, or 3; each R10 is independently selected from hydrogen, C1-C6alkyl, aryl, arylC1-C3alkyl, C3-C6cycloalkyl, halo, and C1-C3haloalkyl; and each R11 is independently selected from hydrogen, C1-C3alkoxy and hydroxy.or a pharmaceutically acceptable salt thereof.