Methods of targeted treatment of frontotemporal lobar degeneration

A method of treating a patient at risk of developing frontotemporal dementia (FTD) or frontotemporal lobar degeneration (FTLD), comprising administering to the patient an effective amount of pharmaceutical composition comprising a compound of Formula (IV):

• or a pharmaceutically acceptable salt thereof
• wherein
• R140 is selected from the group consisting of H, —OH, halo, —CN, —C1-C4alkyl, —C1-C4alkoxyl, —O—C2-C4alkyl-O—C1-C4alkyl, —CF3, —OCF3, —NO2, —C1-C6alkyl-S(O)0-2R53, —NH2, —NR50R51, —C1-C6alkyl-NR50R51 and —N(C1-C6alkyl)2;
• xa and xb denote numbers that are each independently selected from 0, 1 and 2;
• and
• R150 and R160 are independently selected from the group consisting of H, halo, —CN, —CF3, —OCF3, —C1-C6alkyl, —C1-C6alkoxyl, —O—C2-C6alkyl-O—R53, —OR53, —C0-C6alkyl-S(O)0-2—R53, —C0-C6alkyl-C(O)—R53, —C0-C6alkyl-C(O)NR50R51, —C0-C6alkyl-NR52C(O)—R53, —C0-C6alkyl-S(O)2NR50R51, —C0-C6alkyl-NR52S(O)2—R53, —C0-C6alkyl-OC(O)NR50R51, —C0-C6alkyl-NR52C(O)O—R53, —C0-C6alkyl-NR52C(O)NR50R51, —C0-C6alkyl-C(O)O—R53, —C0-C6alkyl-OC(O)—R53, —C0-C6alkyl-aryl, —C0-C6alkyl-heteroaryl, —C0-C6alkyl-cycloalkyl, —C0-C6alkyl-heterocyclyl, —NH2, —NR50R51, —C1-C6alkyl-NR50R51, —O—C2-C6alkyl-NR50R51, —NR53—C2-C6alkyl-NR50R51 and —O-heterocyclyl-R53, wherein each alkyl and heteroalkyl is optionally substituted with one or three substituents independently selected from the group consisting of F, —OH and oxo, and wherein each aryl, heteroaryl, cycloalkyl and heterocyclyl is optionally substituted with one or two substituents independently selected from the group consisting of halo, —CN, —C1-C4alkyl, —C1-C4alkoxyl, —O—C2-C4alkyl-O—C1-C4alkyl, —CF3, —OCF3, —NO2, —C1-C6alkyl-S(O)0-2R53, —NH2, —NR50R51, —C1-C6alkyl-NR50R51 and —N(C1-C6alkyl)2;
• R50 and R51 are independently selected from the group consisting of H, —C1-C6alkyl, —C2-C6alkyl-O—C1-C6alkyl, —C0-C6alkyl-C3-C7cycloalkyl, wherein each alkyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of halo, —OH, amino, —CN or —C1-C4alkyl;
• or
• R50 and R51, together with the N atom to which they are attached, optionally form a 3-10 membered heterocyclic ring, wherein the heterocyclyl is optionally substituted with one to three substituents independently selected from the group consisting of halo, —OH, amino, —CN or —C1-C4alkyl;
• R52 is independently selected from the group consisting of —H, —C1-C6alkyl, —C2-C6alkyl-O—C1-C6alkyl, —C0-C6alkyl-C3-C7cycloalkyl, wherein each alkyl and cycloalkyl is optionally substituted with one or more substituents independently selected from the group consisting of halo, —OH, amino, —CN or —C1-C4alkyl;
• R53 is independently selected from the group consisting of —C1-C6alkyl, —C0-C4alkyl-C3-C7cycloalkyl, —C0-C4alkyl-aryl, —C0-C4alkyl-heteroaryl and —C0-C4alkyl-heterocyclyl, wherein each alkyl, aryl, heteroaryl and heterocyclyl is optionally substituted with one or three substituents independently selected from the group consisting of halo, —OH, amino, —CN or —C1-C4alkyl.