Modulators of the integrated stress pathway

A compound of Formula (I):

• or a pharmaceutically acceptable salt, solvate, hydrate, tautomer, N-oxide, or stereoisomer thereof, wherein:
• D is a bridged bicyclic cycloalkyl, bridged bicyclic heterocyclyl, cubanyl, cyclohexyl, cyclobutyl, or tetrahydropyranyl wherein each bridged bicyclic cycloalkyl, bridged bicyclic heterocyclyl, cubanyl, cyclohexyl, cyclobutyl, or tetrahydropyranyl is optionally substituted on one or more available carbons with 1-4 RX;
• and wherein if the bridged bicyclic heterocyclyl contains a substitutable nitrogen moiety, the substitutable nitrogen may optionally be substituted with RN1;
• L1 is a bond, C1-C6 alkylene, 2-7 membered heteroalkylene, or —O—, wherein C1-C6 alkylene or 2-7 membered heteroalkylene is optionally substituted with 1-5 RL1;
• L2 is C1-C6 alkylene, 2-7 membered heteroalkylene, a bond, —NRN2—, —O—, or —S(O)w— (wherein w is 0, 1 or 2);
• wherein C1-C6 alkylene or 2-7 membered heteroalkylene is optionally substituted with 1-5 RL2;
• R1 is hydrogen or C1-C6 alkyl;
• W is a 3-7-membered saturated, or partially unsaturated, monocyclic nitrogen-containing heterocyclyl;
• wherein the 3-7-membered saturated or partially unsaturated monocyclic heterocyclyl is optionally substituted on one or more available carbons with 1-5 RW;
• and wherein if the 3-7-membered saturated or partially unsaturated monocyclic heterocyclyl contains a substitutable nitrogen moiety, the substitutable nitrogen may be optionally substituted by RN3;
• and wherein W is attached to D through an available nitrogen atom or carbon atom within W;
• A and Z are each independently phenyl or 5-6-membered heteroaryl, wherein each phenyl or 5-6-membered heteroaryl is optionally substituted on one or more available carbons with 1-5 RY;
• and wherein if the 5-6-membered heteroaryl contains a substitutable nitrogen moiety, the substitutable nitrogen may be optionally substituted by RN4;
• each RL1 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, —RBRC, —NRBC(O)RD, —C(O)NRBRC, —C(O)RD, —C(O)OH, —C(O)ORD, —SRE, —S(O)RD, and —S(O)2RD;
• each RL2 is independently selected from the group consisting of hydrogen, 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, and —S(O)2RD;
• 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;
• RN2 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;
• RN3 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;
• RN4 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;
• each RW is independently selected from the group consisting of hydrogen, 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, and —S(O)2RD;
• each RX is independently selected from the group consisting of hydrogen, 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, and —S(O)2RD;
• each RY is independently selected from the group consisting of hydrogen, C1-C6 alkyl, hydroxy-C1-C6 alkyl, halo-C1-C6 alkyl, halo-C1-C6 alkoxy, amino-C1-C6 alkyl, cyano-C1-C6 alkyl, 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, and G1;
• or
• 2 RY groups on adjacent atoms, together with the atoms to which they are attached form a 3-7-membered fused cycloalkyl, 3-7-membered fused heterocyclyl, fused aryl, or 5-6 membered fused heteroaryl each of which is optionally substituted with 1-5 RX;
• each G1 is independently 3-7-membered cycloalkyl, 3-7-membered heterocyclyl, aryl, or 5-6-membered heteroaryl, wherein each 3-7-membered cycloalkyl, 3-7-membered heterocyclyl, aryl, or 5-6-membered heteroaryl is optionally substituted with 1-3 RZ;
• each RZ is independently selected from the group consisting of C1-C6 alkyl, hydroxy-C1-C6 alkyl, halo-C1-C6 alkyl, halo, cyano, —ORA, —NRBRC, —NRBC(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, —C(O)NRBRC, —C(O)RD, or —C(O)ORD;
• each of RB and RC is independently hydrogen or C1-C6 alkyl;
• or
• RB and RC together with the atom to which they are attached form a 3-7-membered heterocyclyl ring optionally substituted with 1-3 RZ;
• each RD is independently 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;
• and
• m is 1 when RF is hydrogen or C1-C6 alkyl, 3 when RF is C1-C6 alkyl, or 5 when RF is halo.