Heterocyclic inhibitors of PCSK9

A method for reducing LDL-C in a subject in need thereof, the method comprising administering a therapeutically effective amount of a compound according to Formula (1):

• or a pharmaceutically acceptable salt thereof, wherein
• A is an optionally substituted 5-membered heteroaryl ring, wherein the substituent is a methyl group;
• Q is selected from the group consisting of optionally substituted:
• C2-C6 alkenyl, C2-C6 haloalkenyl, C1-C6 alkyloxy, C2-C6 alkenyloxy, C1-C6 alkylamino, C2-C6 alkenylamino, C2-C6 alkenylcarboxy, C1-C6 haloalkoxy, C2-C6 haloalkenyloxy, C1-C6 hydroxyalkyl, C2-C6 hydroxyalkenyl, C1-C6 alkylcarboxyamide, C2-C6 alkenylcarboxyamide, C1-C6 alkylsulfanyl, C2-C6 alkenylsulfenyl, C1-C6 alkylsulfenyl, C2-C6 alkenylsulfenyl, C1-C6 alkylsulfonyl, C2-C6 alkenylsulfenyl, C1-C6 alkylsulfonylamino, C2-C6 alkenylsulfonylamino, C4-C7 heterocyclyl, (C1-C3 alkyl)C3-C7 heterocyclyl, (C1-C3 alkyl)C3-C7 cycloalkyl and C3-C7 cycloalkyl;
• wherein D is
• wherein G is selected from the group consisting of —NR1C(O)—, —C(O)NR1—, —S(O)2NR1—, and —NR1S(O)2—;
• wherein R1 is H or methyl and R2 is H,
• or wherein G is —NR1C(O)— and R1 and R2, together with the atoms between them, form an optionally substituted C3-C6 heterocyclic ring, thereby creating a bicyclic or tricyclic ring;
• and
• wherein X1 is CR3 and X2 is N, or X1 is N and X2 is CR3, or both X1 and X2 are CR3;
• wherein R3 is H, C1-C2 alkyl, C1-C2 hydroxyalkyl, C1-C2 alkoxy or C1-C2 alkylamino;
• and
• wherein Y1 is H or methyl and Y2 is
• or Y2 is H or methyl and Y1 is
• or both Y1 and Y2 are independently selected from H or methyl;
• wherein L is selected from the group consisting of —O—, —NH—, —C(O)—, —NH(CH2)m—, C1-C3 alkoxy, C1-C3 alkylamino;
• where m is 1 or 2;
• and
• wherein
• is optionally substituted aryl or optionally substituted heteroaryl with the proviso that
• named relative to the position of attachment to L, is not pyrazolopyridinyl, ortho-substituted pyridine, 4-pyrimidinyl or imidazole;
• and
• wherein R4 is H, NHC(O)CH3, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl.