EAAT2 activators and methods of using thereof

A compound defined by Formula I

• wherein
• Y is O;
• X1 is N;
• X2 is CR3;
• X3 is CR4;
• A is pyridyl, pyrazinyl, pyrimidinyl, triazinyl, or pyridazinyl substituted by 1, 2, 3, or 4 independently selected RA groups;
• R2 is —(CHRE)nR5;
• R5 is 5-6 membered heteroaryl optionally substituted by 1 or 2 independently selected RB groups;
• RE is selected from the group consisting of H, C1-6 alkyl, C1-6 alkoxy, and amino, wherein said C1-6 alkyl is optionally substituted by 1, 2, 3, or 4 independently selected R6 groups;
• R3 and R4 are independently H;
• each RA and RB is independently selected from halo, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, CN, NO2, ORa, SRa, C(O)Rb, C(O)NRcRd, C(O) ORa, OC(O)Rb, OC(O)NRcRd, NRcRd, NRcORd, NRcC(O)Rb, NRcC(O) ORa, NRcC(O)NRcRd, C(═NRe)Rb, C(═NRe)NRcRd, NRcC(═NRe)NRcRd, NRcS(O)Rb, NRcS(O)2Rb, NRcS(O)2NRcRd, S(O)Rb, S(O)NRcRd, S(O)2Rb, and S(O)2NRcRd;
• wherein said C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, and C1-4 haloalkyl are optionally substituted with 1, 2, 3, or 4 independently selected R6 groups;
• each Ra, Rb, Rc, and Rd is independently selected from H, C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl;
• wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C1-4 haloalkyl, C3-10 cycloalkyl, 6-10 membered aryl, 5-10 membered heteroaryl, and 4-10 membered heterocycloalkyl are each optionally substituted with 1, 2, 3, or 4 independently selected R6 groups;
• each Re is independently selected from H, CN, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkylthio, C1-6 alkylsulfonyl, C1-6 alkylcarbonyl, C1-6 alkylaminosulfonyl, carbamyl, C1-6 alkylcarbamyl, di(C1-6 alkyl) carbamyl, aminosulfonyl, C1-6 alkylaminosulfonyl, and di(C1-6 alkyl) aminosulfonyl;
• each R6 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 alkyl, HO—C1-3 alkyl, 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;
• and
• n is 1;
• or a pharmaceutically acceptable salt, ester, or N-oxide thereof.