Modulators of the integrated stress pathway

A compound of Formula (I):

• or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, ester, N-oxide or stereoisomer thereof, wherein:
• D is a bridged bicyclic cycloalkyl, bridged bicyclic heterocyclyl, or cubanyl, wherein each bridged bicyclic cycloalkyl, bridged bicyclic heterocyclyl, or cubanyl is optionally substituted with 1-4 RX;
• and wherein if the bridged bicyclic heterocyclyl contains a substitutable nitrogen moiety, the substitutable nitrogen moiety may be optionally substituted by RN1;
• L1 is C1-C6 alkylene, C1-C6 alkenylene, or 2-7-membered heteroalkylene, wherein each C1-C6 alkylene, C1-C6 alkenylene, or 2-7-membered heteroalkylene is optionally substituted with 1-5 RX;
• R1 and R2 are each independently hydrogen, C1-C6 alkyl, C1-C6 alkoxy-C2-C6 alkyl, hydroxy-C2-C6 alkyl, or silyloxy-C2-C6 alkyl;
• RN1 is selected from the group consisting of hydrogen, C1-C6 alkyl, hydroxy-C2-C6 alkyl, halo-C2-C6 alkyl, amino-C2-C6 alkyl, cyano-C2-C6 alkyl, —C(O)NRBRC, —C(O)RD, —C(O)ORD, and —S(O)2RD;
• Q is C(O) or S(O)2;
• A and W are each independently phenyl or 5-6-membered heteroaryl, wherein each phenyl or 5-6-membered heteroaryl is optionally substituted with 1-5 RY;
• each RX is independently selected from the group consisting of C1-C6 alkyl, hydroxy-C1-C6 alkyl, halo-C1-C6 alkyl, amino-C1-C6 alkyl, cyano-C1-C6 alkyl, oxo, halo, cyano, —ORA, —NRBRC, —NRBC(O)RD, —C(O)NRBRC, —C(O)RD, —C(O)OH, —C(O)ORD, —SRE, —S(O)RD, —S(O)2RD, and G2;
• each RY is independently selected from the group consisting of hydrogen, C1-C6 alkyl, C1-C6 alkenyl, hydroxy-C1-C6 alkyl, hydroxy-C1-C6 alkenyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, amino-C1-C6 alkyl, amido-C1-C6 alkyl, cyano-C1-C6 alkyl, siloxy-C1-C6 alkoxy, hydroxyl-C1-C6 alkoxy, C1-C6 alkoxy-C1-C6 alkyl, C1-C6 alkoxy-C1-C6 alkenyl, C1-C6 alkoxy-C1-C6 alkoxy, oxo, halo, cyano, —ORA, —NRBRC, NRBC(O)RD, —C(O)NRBRC, —C(O)RD, —C(O)OH, —C(O)ORD, —S(RF)m, —S(O)RD, —S(O)2RD, S(O)NRBRC, —NBS(O)2RD, —OS(O)RD, —OS(O)2RD, RFS—C1-C6 alkyl, RDC(O)NRB—C1-C6 alkyl, (RB)(RC)N—C1-C6 alkoxy, RDOC(O)NRB—C1-C6 alkyl, G1, G1-C1-C6 alkyl, G1-N(RB), G1-C1-C6 alkenyl, G1-O—, G1C(O)NRB—C1-C6 alkyl, and G1-NRBC(O);
• or
• 2 RY groups on adjacent atoms, together with the atoms to which they are attached form a fused phenyl, a 3-7-membered fused cycloalkyl ring, a 3-7-membered fused heterocyclyl ring, or a 5-6-membered fused heteroaryl ring, each optionally substituted with 1-5 Rx;
• each G1 or G2 is independently 3-7 membered cycloalkyl, 4-7-membered heterocyclyl, aryl, or 5-6-membered heteroaryl, wherein each 3-7 membered cycloalkyl, 4-7-membered heterocyclyl, aryl, or 5-6-membered heteroaryl is optionally substituted with 1-6 RZ;
• each RZ is independently selected from the group consisting of C1-C6 alkyl, hydroxy-C1-C6 alkyl, halo-C1-C6 alkyl, halo, cyano, oxo, —ORA, —NRBRC, NBC(O)RD, —C(O)NRBRC, —C(O)RD, —C(O)OH, —C(O)ORD, and —S(O)2RD;
• RA is, at each occurrence, independently hydrogen, C1-C6 alkyl, halo-C1-C6 alkyl, —RA1, —C(O)NRBRC, —C(O)RD, or —C(O)ORD;
• each of RB and RC is independently hydrogen, C1-C6 alkyl, hydroxy-C1-C6 alkyl, G1-C1-C6 alkyl, phenyl, 5-6-membered heteroaryl, 3-7 membered cycloalkyl, or 4-7-membered heterocyclyl, wherein each alkyl, phenyl, cycloalkyl, or heterocyclyl is optionally substituted with 1-6 RZ;
• or
• RB and RC together with the atom to which they are attached form a 3-7-membered cycloalkyl or heterocyclyl ring optionally substituted with 1-6 RZ;
• RD is, at each occurrence, independently C1-C6 alkyl, hydroxy-C1-C6 alkyl, C1-C6 alkoxy-C1-C6 alkyl, or halo-C1-C6 alkyl;
• each RE is independently hydrogen C1-C6 alkyl, or halo-C1-C6 alkyl;
• each RF is independently hydrogen, C1-C6 alkyl, or halo;
• each RA1 is 3-7 membered cycloalkyl, or 4-7-membered heterocyclyl;
• m is 1 when RF is hydrogen or C1-C6 alkyl, 3 when RF is C1-C6 alkyl, or 5 when RF is halo;
• and
• t is 0 or 1.