Aryl Ether-Base Kinase Inhibitors

A method for treating or managing a disease or a disorder mediated by AAK1 activity, the method comprising administering to a patient in need thereof a therapeutically effective amount of 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.