Methods and materials for modulating nrf2 pathway

A compound of Formula (II):

• or a pharmaceutically acceptable salt thereof, wherein:
• X1 is selected from N and CR1;
• X2 is selected from N and CR2;
• X3 is selected from N and CR3;
• X4 is selected from N and CR4;
• X5 is selected from N and CR5;
• provided that no more than three of X1, X2, X3, X4, and X5 are N;
• R1, R2, R3, R4, R5, R1, and R11 are each independently selected from H, halo, CN, NO2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, 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, 3, 4, or 5 substituents independently selected from halo, CN, NO2, ORa1, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1 and S(O)2NRc1Rd1;
• R6, R6a, and R7 are each independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl, 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, SRa1, C(O)Rb1, C(O)NRc1Rd1, C(O)ORa1, OC(O)Rb1, OC(O)NRc1Rd1, NRc1Rd1, NRc1C(O)Rb1, NRc1C(O)ORa1, NRc1C(O)NRc1Rd1, NRc1S(O)Rb1, NRc1S(O)2Rb1, NRc1S(O)2NRc1Rd1, S(O)Rb1, S(O)NRc1Rd1, S(O)2Rb1 and S(O)2NRc1Rd1;
• m is an integer from 2 to 20;
• each L is independently selected from N(RN), O, C(═O), S, S(═O), S(═O)2, C1-6 alkylene, C3-7 cycloalkylene, 4-10-membered heterocycloalkylene, 5-10-membered heteroarylene, C6-10 arylene, —(OCH2CH2)x—, —(CH2CH2O)x—, —(OCH(CH3)CH2)x—, —(CH2CH(CH3)O)x—, each of which is optionally substituted with 1 or 2 substituents independently selected from OH, NH2, C(O)OH, SO3H, C1-3 alkylamino, di(C1-3-alkyl)amino, C1-3 haloalkyl, C1-3 alkoxy, and C1-3 haloalkoxy;
• each x is independently an integer from 1 to 2,000;
• each RN is independently selected from H, C1-6 alkyl, C2-6 alkenyl, and C2-6 alkynyl;
• RA is independently selected from H and a targeting ligand capable of selectively binding to a protein;
• each Rb1 is independently selected from H, C1-12 alkyl, C1-4haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-10 cycloalkyl, wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-10 cycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Rg;
• each Ra1, Rc1 and Rd1 is independently selected from H, C1-6 alkyl, C1-4haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-10 cycloalkyl, C(O)Rb2, C(O)NRc2Rd2, C(O)ORa2, NRc2Rd2, S(O)Rb2, S(O)NRc2Rd2, S(O)2Rb2, and S(O)2NRc2Rd2;
• wherein aid C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-10 cycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Rg;
• each Ra2, Rb2, Rc2, and Rd2 is in dependently selected from H, C1-6 alkyl, C1-4haloalkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-10 cycloalkyl;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C3-10 cycloalkyl are each optionally substituted with 1, 2, or 3 substituents independently selected from Rg;
• or any Rc1 and Rd1 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from Rg;
• or any Rc2 and Rd2 together with the N atom to which they are attached form a 4-, 5-, 6-, or 7-membered heterocycloalkyl group optionally substituted with 1, 2, or 3 substituents independently selected from Rg;
• and
• 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, 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.