Methods and materials for increasing level of phosphorylated ampk protein

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• R1 is selected from 5-6 membered heteroaryl and a group of formula:
• wherein said 5-6 membered heteroaryl of R1 is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from R5;
• L1 is C1-4 alkylene, which is optionally substituted with halo or OR4;
• L2 is C1-4 alkylene or L2 is absent;
• X is selected from CR7(OR4), C═O, and C3-6 cycloalkylene;
• or X is absent;
• R7 is selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl;
• R2 and R3 are each independently selected from H, C1-6 alkyl, Cy1, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C(═O)Cy1, and S(═O)2Cy1, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-6 haloalkyl are each optionally substituted with 1 or 2 independently selected Cy1;
• provided that at least one of R2 and R3 is other than H;
• 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;
• or R4 and R2 together with the O atom to which R4 is attached and N atom to which R2 is attached form 5-10 membered heterocycloalkyl, which is optionally substituted with 1 or 2 independently selected Cy1;
• or R2 and R3, together with the N atom to which they are attached, form 4-16 membered heterocycloalkyl ring, which is optionally substituted with 1 or 2 substituents independently selected from R6;
• each R6 is independently selected from C1-6 alkyl, ORa1, C(O)NRc1Rd1, C(O)ORa1, C1-6 haloalkyl, and Cy1, wherein said C1-6 alkyl is optionally substituted with a substituent selected from ORa1, C(O)NRc1Rd1, and C(O)ORa1;
• 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, thio, C1-6 alkylthio, carboxy, amino, C1-6 alkylamino, and di(C1-6 alkyl)amino;
• each Cy1 is independently selected from C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from RCy1;
• 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 heteroaryl, and 4-10 membered 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, C1-4 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkylene, C3-10 cycloalkyl-C1-4 alkylene, (5-10 membered heteroaryl)-C1-4 alkylene, and (4-10 membered heterocycloalkyl)-C1-4 alkylene, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C6-10 aryl, C3-10 cycloalkyl, 5-10 membered heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkylene, C3-10 cycloalkyl-C1-4 alkylene, (5-10 membered heteroaryl)-C1-4 alkylene, and (4-10 membered 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 heterocycloalkyl, which is 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 heteroaryl, 4-10 membered heterocycloalkyl, C6-10 aryl-C1-4 alkylene, C3-10 cycloalkyl-C1-4 alkylene, (5-10 membered heteroaryl)-C1-4 alkylene, (4-10 membered heterocycloalkyl)-C1-4 alkylene, amino, C1-6 alkylamino, di(C1-6 alkyl)amino, thio, 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,
• provided that when R4 is H, then R2 and R3 are both independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, Cy3, C(═O)Cy3, and S(═O)2Cy3, wherein said C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, and C2-6 alkynyl are each substituted with 1 or 2 independently selected Cy3, and each of said Cy3 is independently selected from C3-10 cycloalkyl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl, each of which is optionally substituted with 1, 2, 3, 4, or 5 substituents independently selected from RCy1.