Methods and materials for increasing level of phosphorylated AMPK protein

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is a group of formula
• L1 is C1-4 alkylene optionally substituted with halo or OR4;
• L2 is C1-4 alkylene or L2 is absent;
• X is selected from CR7(OR4) and C═O;
• or X is absent;
• R7 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
• R2 is —CH2-phenyl, wherein said phenyl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from RCy1;
• R3 is —CH2-(5-10 membered monocyclic or bicyclic heteroaryl), wherein said heteroaryl is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from RCy1;
• R4 is selected from H, C(O)Rb1, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl, each of which is optionally substituted with 1, 2, or 3 substituents independently selected from Rg;
• m is 0, 1, 2, 3, or 4;
• n is 0, 1, 2, or 3;
• each R5 is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, —SH, C1-6 alkylthio, carboxy, amino, C1-6 alkylamino, and di(C1-6 alkyl)amino;
• each RCy1 is independently selected from halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cy2, ORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1S(O)2Rb1, S(O)2Rb1, and S(O)2NRc1Rd1;
• wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Cy2, halo, CN, NO2, ORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1S(O)2Rb1, S(O)2Rb1, and S(O)2NRc1Rd1;
• each Cy2 is independently selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered monocyclic or bicyclic heteroaryl, and 4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from RCy2;
• each RCy2 is independently selected from halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, ORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, NRc1Rd1 NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1S(O)2Rb1, S(O)2Rb1, and S(O)2NRc1Rd1;
• wherein said C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl are each optionally substituted with 1, 2, or 3 substituents independently selected from halo, CN, NO2, ORa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1S(O)2Rb1, S(O)2Rb1, and S(O)2NRc1Rd1;
• each Ra1, Rb1, Rc1, and Rd1 is independently selected from H, C1-6 alkyl, C1-4haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered monocyclic or bicyclic heteroaryl, 4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl, C6-10 aryl-C1-4 alkylene, C3-10 cycloalkyl-C1-4 alkylene, (5-10 membered monocyclic or bicyclic heteroaryl)-C1-4 alkylene, and (4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl)-C1-4 alkylene, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered monocyclic or bicyclic heteroaryl, 4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl, C6-10 aryl-C1-4 alkylene, C3-10 cycloalkyl-C1-4 alkylene, (5-10 membered monocyclic or bicyclic heteroaryl)-C1-4 alkylene, and (4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl)-C1-4 alkylene are each optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from Rg;
• or any Rc1 and Rd1 together with the N atom to which they are attached form a 4-7 membered monocyclic heterocycloalkyl optionally substituted with 1, 2, or 3 substituents independently selected from Rg;
• each Rg is independently selected from OH, NO2, CN, halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, cyano-C1-3 alkylene, HO—C1-3 alkylene, C6-10 aryl, C6-10 aryloxy, C3-10 cycloalkyl, 5-10 membered monocyclic or bicyclic heteroaryl, 4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl, C6-10 aryl-C1-4 alkylene, C3-10 cycloalkyl-C1-4 alkylene, (5-10 membered monocyclic or bicyclic heteroaryl)-C1-4 alkylene, (4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl)-C1-4 alkylene, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, —SH, C1-6 alkylthio, C1-6 alkylsulfinyl, C1-6 alkylsulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl)carbamyl, carboxy, C1-6 alkylcarbonyl, C1-6 alkoxycarbonyl, C1-6 alkylcarbonylamino, C1-6 alkylsulfonylamino, aminosulfonyl, C1-6 alkylaminosulfonyl, di(C1-6 alkyl)aminosulfonyl, aminosulfonylamino, C1-6 alkylaminosulfonylamino, di(C1-6 alkyl)aminosulfonylamino, aminocarbonylamino, C1-6 alkylaminocarbonylamino, and di(C1-6 alkyl)aminocarbonylamino;
• wherein
• each 5-10 membered monocyclic or bicyclic heteroaryl independently has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, sulfur, and oxygen;
• and
• each 4-10 membered monocyclic or fused or spiro bicyclic heterocycloalkyl and each 4-7 membered monocyclic heterocycloalkyl independently has 1, 2, 3, or 4 heteroatom ring members independently selected from nitrogen, oxygen, and sulfur and contains 0 to 3 double bonds.