Compounds and methods for treating corona viruses

A compound of formula (I″),

• or a pharmaceutically acceptable salt thereof, wherein:
• Ring A is selected from the group consisting of naphthyl, anthracenyl, phenanthrenyl, 8-14 membered bicyclic or tricyclic heteroaryl, 8-12 membered bicyclic or tricyclic heterocyclyl, and 8-12 membered partially unsaturated bicyclic carbocyclyl, wherein the naphthyl, 8-14 membered bicyclic or tricyclic heteroaryl, and 8-12 membered partially unsaturated bicyclic carbocyclyl are optionally substituted by one or more (e.g., one, two, three, or four) R1,
• wherein when ring A is 8-12 membered bicyclic heterocyclyl or 8-12 membered partially unsaturated bicyclic carbocyclyl, R3 is C1-6 alkoxy optionally substituted with one or more (e.g., one, two, three, or four) R3a;
• each X is independently selected from the group consisting of CH2, CH, NRh, and O;
• each R is independently D, C1-6 alkyl or halo when Rx is substituted on a carbon atom or each Rx is independently C1-6 alkyl when Rx is substituted on a nitrogen atom;
• m is 0, 1, 2, 3, or 4;
• is a single bond or double bond;
• n is 1 or 2;
• each R1 is independently selected from the group consisting of phenyl, 5-9 membered heteroaryl, C3-7 carbocyclyl, 3-7 membered heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) R1a, C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, C1-6 alkyl optionally substituted with hydroxy, C2-6 alkenyl optionally substituted with C3-6 cycloalkyl or phenyl substituted with C0-6alkyl, C2-6 alkynyl optionally substituted with one or more (e.g., one, two, three, or four) halo, C1-6 alkoxy optionally substituted with phenyl, —O—C1-6 alkylene-C1-6 alkoxy, —C(O)—C1-6 alkyl, —C(O)ORi, —S(O)tC1-6alkyl, —S—C1-6 haloalkyl, —OS(O)tC1-6haloalkyl, —NRjRk, —C(O)NRgRh, —O-phenyl, —B(ORm)2, and hydroxy, wherein the phenyl and 5-9 membered heteroaryl are optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of halo, cyano, phenyl, 3-7 membered heterocyclyl, C1-6 alkyl, C1-6alkylene-(3-7 membered heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) halo), C1-6alkylene substituted with hydroxy, C1-6 alkylene-NRARB, —C(O)-3-6 membered heterocyclyl, hydroxy, C1-6 haloalkyl, C1-6 alkoxy, and —C(O)—C1-6 alkyl;
• wherein t is 0, 1, or 2;
• R1a is selected from the group consisting of oxo, halo, C1-6haloalkyl, and C1-6alkoxy;
• R5 is selected from the group consisting of H, halo, and C1-6 alkyl;
• R6 is selected from the group consisting of H, halo, and C1-6 alkyl;
• R7 is selected from H and C1-6 alkyl;
• R2 is selected from the group consisting of halo, C1-6 alkyl, C2-6 alkynyl, C1-6 haloalkyl, C1-6 alkoxy, and C3-6 cycloalkyl;
• R3 is selected from the group consisting of C1-20 alkoxy, hydroxy, C0-6 alkylene-(3-10 membered heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6alkyl, (C1-6alkylene-OH), —C(O)O—C1-6 alkyl, and —NReRf, —O—C3-7 cycloalkyl optionally substituted with —NRcRd, —(C0-6alkylene)-O-(3-9 membered heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl, benzyl and —C(O)O—C1-6 alkyl), C1-6 alkyl optionally substituted with —NRcRd, —O-(5-6 membered heteroaryl), C0-6 alkylene-CN, C0-6 alkylene-C(O)O(C1-6alkyl), C0-6 alkylene-C(O)NReRf, and —NRAARBB, wherein the C1-20 alkoxy is optionally substituted with one or more (e.g., one, two, three, or four) R3a;
• R4 is selected from the group consisting of H, C1-6 alkyl, C2-6 alkynyl optionally substituted with phenyl or 5-6 membered heteroaryl, halo, hydroxy, and —NReRf;
• or
• R3 and R4, together with the atoms to which they are attached, combine to form an aromatic or non-aromatic 5-10 membered monocyclic or bicyclic ring fused to the phenyl, wherein the 5-10 membered ring comprises at least one heteroatom, wherein the 5-10 membered ring is optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl optionally substituted with —NRcRd, C3-7 cycloalkyl, phenyl, 5-6 membered heteroaryl, —(C0-6 alkylene)-C(O)NReRf, —C(O)—C1-6heteroalkyl, —C(O)—NCH3OCH3, —(C0-6 alkylene)-NRcRd, —(C0-6 alkylene)-C1-6 alkoxy, —(C0-6 alkylene)-OH, oxo, —C(O)OH, and —(C0-6 alkylene)-3-7 membered heterocyclyl optionally substituted with C1-6alkyl, wherein the aromatic or non-aromatic 5-10 membered monocyclic or bicyclic ring fused to the phenyl is not an imidazole;
• RAA and RBB are independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, S(O)2C1-6 alkyl, —C(O)—C1-6 alkyl, C1-20 alkylene-NRcRd, 3-6 membered heterocyclyl optionally substituted with oxo, 5-6 membered heteroaryl optionally substituted with C1-6 alkyl or C1-6 alkoxy, —(C0-6 alkylene)-phenyl, —(C0-20 alkylene)-(3-10 membered heterocyclyl), and —(C0-6 alkylene)-C3-6 cycloalkyl, wherein the C1-6 alkyl, C1-6 alkylene, 3-10 membered heterocyclyl, and C3-6 cycloalkyl are each optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl, hydroxy and C1-6 alkoxy;
• each RA and RB are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, S(O)2C1-6 alkyl, —C(O)—C1-6 alkyl, C1-6 alkylene-NRcRd, 3-6 membered heterocyclyl optionally substituted with oxo, 5-6 membered heteroaryl optionally substituted with C1-6 alkyl or C1-6 alkoxy, —(C0-6 alkylene)-phenyl, and —(C0-6 alkylene)-C3-6 cycloalkyl, wherein the C1-6 alkyl, C1-6 alkylene and C3-6 cycloalkyl are each optionally substituted with hydroxy or C1-6 alkoxy;
• each Rc and Rd are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, benzyl, and —C(O)OC1-6 alkyl, or
• Rc and Rd can be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocyclyl;
• each Re and Rf are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, —C(O) C1-6alkyl, —C(O)OC1-6alkyl, and —S(O)2C1-6alkyl;
• each Rg, Rh, and Ri are independently, for each occurrence, H or C1-6 alkyl;
• and
• each Rj and Rk are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl optionally substituted with phenyl, C1-6 haloalkyl, —C(O) C1-6alkyl, —S(O)2C1-6alkyl, and —C(O)OC1-6alkyl;
• each R3a is independently selected from the group consisting of D, C1-6 alkyl, —NRARB, C1-6 alkoxy, hydroxy, —C(O)NRcRd, 3-10 membered heterocyclyl, phenyl, 5-6 membered heteroaryl, and —(C0-6 alkylene)-(C3-6 cycloalkyl optionally substituted with NRcRd), wherein the 3-10 membered heterocyclyl and 5-6 membered heteroaryl are optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of halo, hydroxy, C1-6 alkyl optionally substituted with one or more (e.g., one, two, three, or four) D, C1-6 haloalkyl, —C(O)OC1-6 alkyl, C1-6 alkyelene-C3-7 cycloalkyl, phenyl, benzyl, C1-6 alkylene-OH, and C0-6 alkylene-C1-6 alkoxy;
• and
• each Rm is independently selected from hydrogen and C1-6alkyl or two (ORm) groups can be taken together with the boron atom to which they are attached to form pinacol ester;
• with the proviso that, when ring A is naphthyl, R4 is selected from the group consisting of hydrogen, —F, —Cl, C1-6 alkyl, and —NReRf;
• R5 is hydrogen;
• R6 is hydrogen or halo;
• X is CH2;
• and n is 1;
• R2 is selected from the group consisting of halo, C1-6 alkyl, C2-6 alkynyl, C1-6 alkoxy, and C3-6 cycloalkyl;
• R3 is selected from the group consisting of C1-6 alkoxy, hydroxy, C1-6 alkylene-(3-10 membered heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) RXX), 3 membered heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) RXX, 4 membered heterocyclyl substituted with one or more (e.g., one, two, three, or four) RXX, 5 membered partially unsaturated heterocyclyl, 5 membered saturated heterocyclyl that has the point of attachment (to the phenyl) on the carbon atom of the heterocyclyl, 5 membered saturated heterocyclyl substituted with at least 2 (e.g., 2, 3, or 4) of RXX, 6-membered heterocyclyl with at least 2 (e.g., 2, 3, or 4) of RXX substituted on the carbon atoms of the heterocyclyl, —O—C3-7 cycloalkyl optionally substituted with —NRcRd, —(C0-6alkylene)-O-(3-9 membered heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl, benzyl and —C(O)O-C1-6 alkyl), C1-6 alkyl optionally substituted with —NRcRd, —O-5-6 membered heteroaryl, C0-6 alkylene-CN, C0-6 alkylene-C(O)O(C1-6alkyl), C0-6 alkylene-C(O)NReRf, and —NRAARBB, wherein the C1-6 alkoxy is optionally substituted with one or more (e.g., one, two, three, or four) R3a;
• each RXX is independently selected from the group consisting of C1-6alkyl, (C1-6alkylene)-OH, —C(O)O—C1-6 alkyl, and —NReRf, and
• RAA and RBB are independently selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, —C(O)—C1-6 alkyl, —(C0-6 alkylene)-phenyl, and —(C0-6 alkylene)-C3-6 cycloalkyl, wherein the C1-6 alkyl, C1-6 alkylene and C3-6 cycloalkyl are each optionally substituted with hydroxy or C1-6 alkoxy, and at least one of RAA and RBB is not hydrogen;
• or RAA is hydrogen and RBB is C1-6 alkylene-NRcRd.

A compound of formula (I-1″),

• or a pharmaceutically acceptable salt thereof, wherein:
• each R1 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, halo, and —CN;
• n is 0, 1, or 2;
• each of R2, R3, R4, and R6 is independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, halo, and —CN;
• and
• R5 is C1-6 alkylene-C(O)NH2, wherein each hydrogen of NH2 is optionally substituted.

A compound of formula (II′),

• or a pharmaceutically acceptable salt thereof,
• wherein
• Ring A is phenyl optionally substituted with one or more (e.g., one, two, three, or four) R1;
• each X is independently selected from the group consisting of CH2, CH, NH, and O;
• each Rx is independently C1-6 alkyl or halo when Rx is substituted on a carbon atom or each Rx is independently C1-6 alkyl when Rx is substituted on a nitrogen atom;
• m is 0, 1, or 2;
• is a single bond or double bond;
• n is 1 or 2;
• each R1 is independently selected from the group consisting of phenyl, 5-6 membered heteroaryl, C3-7 carbocyclyl, 3-7 membered heterocyclyl, C1-6 haloalkyl, halo, C1-6 alkyl, C1-6 alkoxy, —O—(C0-6 alkylene)-phenyl, —S—C1-6alkyl, —S—C1-6 haloalkyl, —NReRf, and hydroxy, wherein the phenyl and 5-6 membered heteroaryl are optionally substituted with one or more (e.g., one, two, three, or four) substituents each selected from the group consisting of halo, C1-6 alkyl optionally substituted with 3-7 membered heterocyclyl, C1-6 alkylene-NRARB, C1-6 haloalkyl, and C1-6 alkoxy;
• R2 is selected from the group consisting of halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C3-6 cycloalkyl;
• R3 is selected from the group consisting of C1-6 alkoxy, hydroxy, 3-8 membered heterocyclyl optionally substituted with C1-6alkyl, —O—C3-7 cycloalkyl optionally substituted with —NRcRd, —O-3-8 membered heterocyclyl optionally substituted with —C(O)O—C1-6 alkyl, C1-6 alkyl optionally substituted with —NRcRd, —O-5-6 membered heteroaryl, C0-6 alkylene-CN, C0-6 alkylene-C(O)NReRf, and —NRARB, wherein the C1-6 alkoxy is optionally substituted with one or more (e.g., one, two, three, or four) R3a,
• R4 is selected from the group consisting of H, C1-6 alkyl, halo, hydroxy, and —NReRf, or
• R3 and R4, together with the atoms to which they are attached, combine to form an aromatic or non-aromatic 5-10 membered monocyclic or bicyclic ring fused to the phenyl, wherein the 5-10 membered ring comprises at least one heteroatom, wherein the 5-10 membered ring is optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, phenyl, 5-6 membered heteroaryl, —(C0-6 alkylene)-C(O)NReRf, —C(O)—C1-6heteroalkyl, —(C0-6 alkylene)-NRcRd, —(C0-6 alkylene)-C1-6 alkoxy, —(C0-6 alkylene)-OH, oxo, —C(O)OH, and —(C0-6 alkylene)-3-7 membered heterocyclyl optionally substituted with C1-6alkyl;
• R5 is selected from the group consisting of H, halo, and C1-6 alkyl;
• R6 is selected from the group consisting of H, halo, and C1-6 alkyl;
• each R3a is independently selected from the group consisting of C1-6 alkyl, —NRARB, C1-6 alkoxy, hydroxy, —C(O)NRcRd, 3-8 membered heterocyclyl, phenyl, and —(C0-6 alkylene)-(C3-6 cycloalkyl optionally substituted with NRcRd), wherein the 3-8 membered heterocyclyl is optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of halo, hydroxy, C1-6 alkyl, C1-6 haloalkyl, —C(O)OC1-6 alkyl, C1-6 alkyelene-C3-7 cycloalkyl, benzyl, C1-6 alkylene-OH, and C1-6 alkylene-C1-6 alkoxy,
• each RA and RB are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, C1-6 alkoxy, S(O)2C1-6 alkyl, —C(O)—C1-6 alkyl, C1-6 alkylene-NRcRd, 3-6 membered heterocyclyl optionally substituted with oxo, 5-6 membered heteroaryl optionally substituted with C1-6 alkyl or C1-6 alkoxy, —(C0-6 alkylene)-phenyl, and —(C0-6 alkylene)-C3-6 cycloalkyl, wherein the C1-6 alkyl, C1-6 alkylene and C3-6 cycloalkyl are each optionally substituted with hydroxy;
• each Rc and Rd are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, benzyl, and —C(O)OC1-6 alkyl, or
• Rc and Rd can be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocyclyl;
• and
• each Re and Rf are independently, for each occurrence, H or C1-6 alkyl.

A compound of formula (II″),

• or a pharmaceutically acceptable salt thereof, wherein
• Ring A is phenyl optionally substituted with one or more (e.g., one, two, three, or four) R1;
• each X is independently selected from the group consisting of CH2, CH, NH, and O;
• each R is independently C1-6 alkyl or halo when Rx is substituted on a carbon atom or each Rx is independently C1-6 alkyl when Rx is substituted on a nitrogen atom;
• m is 0, 1, or 2;
• is a single bond or double bond;
• n is 1 or 2;
• each R1 is independently selected from the group consisting of phenyl, 5-6 membered heteroaryl, C3-7 carbocyclyl, 3-7 membered heterocyclyl, C1-6 haloalkyl, halo, C1-6 alkyl, C1-6 alkoxy, —O—(C0-6 alkylene)-phenyl, —S—C1-6alkyl, —S—C1-6 haloalkyl, —NReRf, and hydroxy, wherein the phenyl and 5-6 membered heteroaryl are optionally substituted with one or more (e.g., one, two, three, or four) substituents each selected from the group consisting of halo, C1-6 alkyl optionally substituted with 3-7 membered heterocyclyl, C1-6 alkylene-NRARB, C1-6 haloalkyl, and C1-6 alkoxy;
• R2 is selected from the group consisting of halo, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, and C3-6 cycloalkyl;
• R3 is selected from the group consisting of C1-6 alkoxy, 3-8 membered heterocyclyl optionally substituted with C1-6alkyl, —O—C3-7 cycloalkyl optionally substituted with —NRcRd, —O-3-8 membered heterocyclyl optionally substituted with —C(O)O—C1-6 alkyl, C2-6 alkyl optionally substituted with —NRcRd, —O-5-6 membered heteroaryl, C0-6 alkylene-C(O)NReRf, and —NRARB, wherein the C1-6 alkoxy is substituted with one or more (e.g., one, two, three, or four) R3a, and wherein R3 is not —N(H)C(O)CH3 or —NH2;
• R4 is selected from the group consisting of H, C1-6 alkyl, halo, hydroxy, and —NReRf, or
• R3 and R4, together with the atoms to which they are attached, combine to form an aromatic or non-aromatic 5-10 membered monocyclic or bicyclic ring fused to the phenyl, wherein the 5-10 membered ring comprises at least one heteroatom, wherein the 5-10 membered ring is optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl, C3-7 cycloalkyl, phenyl, 5-6 membered heteroaryl, —(C0-6 alkylene)-C(O)NReRf, —C(O)—C1-6heteroalkyl, —(C0-6 alkylene)-NRcRd, —(C0-6 alkylene)-C1-6 alkoxy, —(C0-6 alkylene)-OH, oxo, —C(O)OH, and —(C0-6 alkylene)-3-7 membered heterocyclyl optionally substituted with C1-6alkyl;
• R5 is selected from the group consisting of H, halo, and C1-6 alkyl;
• R6 is selected from the group consisting of H, halo, and C1-6 alkyl;
• each R3a is independently selected from the group consisting of C1-6 alkyl, —NRARB, C1-6 alkoxy, hydroxy, —C(O)NRcRd, 3-8 membered heterocyclyl, phenyl, and —(C0-6 alkylene)-(C3-6 cycloalkyl optionally substituted with NRcRd), wherein the 3-8 membered heterocyclyl is optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of halo, hydroxy, C1-6 alkyl, C1-6 haloalkyl, —C(O)OC1-6 alkyl, C1-6 alkyelene-C3-7 cycloalkyl, benzyl, C1-6 alkylene-OH, and C1-6 alkylene-C1-6 alkoxy,
• each RA and RB are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, C1-6 alkoxy, S(O)2C1-6 alkyl, —C(O)—C1-6 alkyl, C1-6 alkylene-NRcRd, 3-6 membered heterocyclyl optionally substituted with oxo or —C(O)O—C1-6 alkyl, 5-6 membered heteroaryl optionally substituted with C1-6 alkyl or C1-6 alkoxy, —(C0-6 alkylene)-phenyl, and —(C0-6 alkylene)-C3-6 cycloalkyl, wherein the C1-6 alkyl, C1-6 alkylene and C3-6 cycloalkyl are each optionally substituted with hydroxy;
• each Rc and Rd are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, benzyl, and —C(O)OC1-6 alkyl, or
• Rc and Rd can be taken together with the nitrogen atom to which they are attached to form a 3-7 membered heterocyclyl;
• and
• each Re and Rf are independently, for each occurrence, H or C1-6 alkyl.

The compound of any one of claim 116-118, wherein the compound is a compound of formula (IIb′):

• or a pharmaceutically acceptable salt thereof, wherein:
• s is 0, 1, 2, or 3;
• and
• R1-R6 are as defined in claim 119.

A compound of formula (III″),

• or a pharmaceutically acceptable salt thereof, wherein:
• Ring A is selected from naphthyl and 8-12 membered bicyclic heteroaryl, wherein the naphthyl and 8-12 membered bicyclic are optionally substituted with one or more (e.g., one, two, three, or four) R1;
• Y1 is N or CR6;
• Y2 is N or CR4;
• Y3 is N or CR5,
• Y4 is N or CR3;
• Y5 is N or CR2;
• each X is independently selected from the group consisting of CH2, CH, NRh, and O, wherein each Rh is independently H or C1-6 alkyl;
• is a single bond or double bond;
• each Rx is independently C1-6 alkyl or halo;
• n is 1 or 2;
• m is 0, 1, or 2;
• each R1 is independently selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, halo, and —CN;
• R2 is selected from the group consisting of halo, C1-6 alkyl, C1-6 haloalkyl, and C1-6 alkoxy;
• R3 is selected from the group consisting of C1-6 alkyl, C1-6 alkoxy, and hydroxy, wherein the C1-6 alkoxy is optionally substituted with one or more (e.g., one, two, three, or four)—NRARB or 3-8 membered heterocyclyl optionally substituted with C1-6alkyl;
• R4 is selected from the group consisting of H, C1-6 alkyl, halo, and hydroxy;
• R5 is selected from the group consisting of H, halo, and C1-6 alkyl;
• R6 is selected from the group consisting of H, halo, and C1-6 alkyl;
• and
• each RA and RB are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, and C1-6 haloalkyl.

A compound of formula (IV″),

• or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
• each R1 is independently selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, and C1-6 alkyl;
• n is 0, 1, or 2;
• (A) R2 is C1-6 alkyl or halo;
• R3 is selected from the group consisting of C1-6 alkoxy, hydroxy, —C(O)—C1-6alkyl;
• —O-(3-8 membered oxygen-containing heterocyclyl optionally substituted with one or more (e.g., one, two, three, or four) C1-6 alkyl, —NRARB, and nitro, wherein the C1-6 alkoxy is optionally substituted with one or more (e.g., one, two, three, or four) R3a, and wherein if R3 is hydroxy, nitro, NH2, NHCH3, or N(CH3)2, neither R7 nor R8 is methyl;
• R4 is H, C1-6 alkyl, halo, and hydroxy;
• or
• (B) R2 is selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, and C1-6 alkoxy;
• R3 and R4, together with the atoms to which they are attached, combine to form:
• i) an aromatic or non-aromatic 5 membered monocyclic ring fused to the phenyl, wherein the 5-membered ring has at least one nitrogen connected to the phenyl at the R3 position or two oxygens, or
• ii) an aromatic or non-aromatic 6 membered monocyclic ring fused to the phenyl, wherein the 6 membered ring has one and only one nitrogen, the nitrogen connected to the phenyl at the R3 position, and the remaining atoms in the ring are carbon,
• wherein the 5 or 6 membered ring is optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of oxo, C1-6 alkyl optionally substituted with hydroxy or —NRcRd, —(C0-6 alkylene)-3-7 membered heterocyclyl optionally substituted with C1-6alkyl;
• R5 is selected from the group consisting of H, halo, and C1-6 alkyl;
• R6 is selected from the group consisting of H, halo, and C1-6 alkyl;
• R7 is selected from the group consisting of hydrogen, C1-6 alkyl optionally substituted with C1-6 alkoxy, C2-6 alkynyl, C1-6 haloalkyl, cyano, and 3-8 membered heterocyclyl optionally substituted with C1-6 alkyl;
• R8 is hydrogen or C1-6 alkyl;
• each R3a is independently selected from the group consisting of C1-6 alkyl, —NReRf, and 3-8 membered heterocyclyl, wherein the 3-8 membered heterocyclyl is optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of halo, hydroxy, C1-6 alkyl, and C1-6 haloalkyl;
• each RA and RB are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, S(O)2C1-2 alkyl, —C(O)-unsubstituted C1-6 alkyl, 3-6 membered unsaturated heterocyclyl optionally substituted with one oxo, 5-6 membered heteroaryl substituted with C1-6 alkyl or C1-6 alkoxy, and pyrazolyl, wherein the C1-6 alkyl is optionally substituted with one or more (e.g., one, two, three, or four) hydroxy and/or one NH2, wherein if one of RA and RB is —C(O)-unsubstituted C1-6 alkyl, the other of RA and RB is not H, and wherein RA and RB are not-(CH2)2NH2 or —CH2C(CH3)2NH2;
• each Rc and Rd are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, and —C(O)OC1-6 alkyl, and
• each Re and Rf are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, and —C(O)OC1-6alkyl,
• wherein the compound is not a compound represented by:
• or a stereoisomer or a pharmaceutically acceptable salt thereof.

A compound of formula (VI″):

• or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
• is
• or an optionally substituted phenyl;
• X is NR9 or a bond;
• Y is NR9, CH2, or a bond;
• R9 is selected from H and C1-6alkyl;
• is a nitrogen containing 4-6 membered heterocyclylene or 4-6 membered heterocycle fused to phenyl;
• each of X1, X2, x3, X4, X3, and X6 is CH or N, wherein the CH may be substituted with R1;
• wherein
• when
• is
• is not a 6-membered monocyclic heterocyclylene;
• each R1 is independently selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, C1-6 alkyl, C1-6 alkoxy, —NReRf, 3-8 membered heterocyclyl, and 5-6 membered heteroaryl;
• n is 0, 1, or 2;
• each of R2, R3, R4, R5, and R6 is independently selected from the group consisting of hydrogen, C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, —NReRf, C1-6 alkoxy, and C1-6 alkyl;
• R7 is selected from the group consisting of C1-6 alkyl optionally substituted with C1-6 alkoxy, C2-6 alkynyl, C1-6 haloalkyl, cyano, and 3-8 membered heterocyclyl optionally substituted with C1-6 alkyl;
• R8 is hydrogen;
• or
• R7 and R8 may be taken together with the carbon to which they are attached to form a 3-4 membered cycloalkyl or heterocyclyl ring;
• and
• each Re and Rf are independently, for each occurrence, selected from the group consisting of H, C1-6 alkyl, and —C(O)OC1-6alkyl.

A compound of formula (VII″):

• or a stereoisomer or a pharmaceutically acceptable salt thereof, wherein:
• ring A is selected from:
• Z is CH2 or NH, wherein any hydrogen atom of the CH2 or NH may be substituted with R1;
• each R1 is independently selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, C1-6 alkyl, C1-6 alkoxy, —S(O)t(C1-6alkyl;
• —NReRf, 3-8 membered heterocyclyl, and 5-6 membered heteroaryl;
• t is 0, 1, or 2;
• n is 0, 1, or 2;
• each of R2, R3, R4, R5, and R6 is independently selected from the group consisting of hydrogen, C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, —NReRf, C1-6 alkoxy, and C1-6 alkyl;
• or R3 and R4 may be taken together with the atoms to which they are attached to form an aromatic 5-6 membered monocyclic ring fused to the phenyl to which R3 and R4 are attached;
• wherein the 5-6 membered ring is optionally substituted with one or more (e.g., one, two, three, or four) C1-6 alkyl optionally substituted with hydroxy or —NRcRd;
• R7 is hydrogen or C1-6 alkyl;
• R8 is hydrogen, C1-6 alkyl, or C1-6haloalkyl;
• R9 is hydrogen or C1-6 alkyl;
• R10 is (5-6 membered heteroarylene)-(C0-6alkylene)-R11;
• R11 is 3-7 membered heterocyclyl or —NRgRh, and
• R12 and R13 are hydrogen;
• or
• R7 and R9 may be taken together with the atoms to which they are attached to form a 5-6 membered heterocycle fused to the phenyl to which R9 is attached;
• R9 and R10 may be taken together with the atoms to which they are attached to form 6-membered heterocycle or cyclohexane ring fused to the phenyl to which R9 and R10 are attached;
• R12 and R13 may be taken together with the atoms to which they are attached to form phenyl ring fused to the ring to which R12 and R13 are attached;
• each Rc and Rd are independently H or C1-6 alkyl;
• and
• each Re and Rf are independently selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocyclyl, and 5-6 membered heteroaryl, wherein the C3-6 cycloalkyl, 3-7 membered heterocyclyl and 5-6 membered heteroaryl are optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl, halogen, —OH, —C(O)OC1-6alkyl, and C1-6 alkoxy;
• each Rg and Rh are independently selected from the group consisting of H, C1-6 alkyl, C3-6 cycloalkyl, 3-7 membered heterocyclyl, and 5-6 membered heteroaryl, wherein the C3-6 cycloalkyl, 3-7 membered heterocyclyl and 5-6 membered heteroaryl are optionally substituted with one or more (e.g., one, two, three, or four) substituents each independently selected from the group consisting of C1-6 alkyl, halogen, —OH, —C(O)OC1-6alkyl, and C1-6 alkoxy, wherein when Rg is hydrogen, Rh is not hydrogen;
• wherein when R10 is (5-6 membered heteroarylene)-(C0-6alkylene)-(3-7 membered heterocyclyl), and R3 is —NRcRd, R8 is hydrogen;
• and
• wherein when Rg or Rh is C3-6 cycloalkyl or 3-7 membered heterocyclyl and R3 is —NReRf, Re or Rf is not 3-7 membered heterocyclyl.

A compound of formula (VIII″):

• or a stereoisomer or a pharmaceutically acceptable salt thereof;
• wherein
• B is selected from:
• each R1 is independently selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, and C1-6 alkyl;
• n is 0, 1, or 2;
• each of R2, R3, R4, R5, and R6 is independently selected from the group consisting of hydrogen, C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, —NReRf, NO2, C1-6 alkoxy, and C1-6 alkyl;
• or
• R4 and R5 may be taken together with the atoms to which they are attached to form 5-membered heteroaryl fused to the phenyl to which R4 and R5 are attached;
• R9 is hydrogen or C1-6 alkyl;
• each R10 is independently selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, —NReRf, NO2, C1-6 alkoxy, C1-6 alkyl, and C(O)NH(C1-6 alkylene) Ph wherein the Ph is optionally substituted with halogen;
• m is 0, 1, or 2;
• R6 and R9 may be taken together with the atoms to which they are attached to form piperidine ring fused to the phenyl to which R6 is attached;
• each of R7 and R8 is independently hydrogen, C1-6 alkyl, or C1-6haloalkyl, or R7 and R8 may be taken together with the atom to which they are attached to form 3-4 membered cycloalkyl or heterocyclyl ring;
• wherein when R9 is methyl, R7 and R8 are not methyl;
• wherein when R9 is hydrogen, at least one of R2 and R6 is not hydrogen;
• each of Re and Rf is independently selected from the group consisting of hydrogen, C1-6 alkyl, and —C(O)CH2Ph.

A compound of formula (IX″):

• or a stereoisomer or a pharmaceutically acceptable salt thereof;
• wherein
• each R1 is independently selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, and C1-6 alkyl;
• n is 0, 1, or 2;
• R2 is C1-6 alkyl;
• R3 is selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, —NReRf, NO2, C1-6 alkoxy, and C1-6 alkyl;
• R6 is hydrogen or C1-6 alkyl;
• and
• each of Re and Rf is independently selected from hydrogen and C1-6 alkyl.

A compound of formula (X″):

• or a stereoisomer or a pharmaceutically acceptable salt thereof;
• wherein
• each R1 is independently selected from the group consisting of C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, and C1-6 alkyl;
• n is 0, 1, or 2;
• R2 is C1-6 alkyl;
• and
• R3 is selected from the group consisting of C1-6 alkyl, C1-6 haloalkyl, C1-6 haloalkoxy, halo, —CN, —NReRf, NO2, C1-6 alkoxy optionally substituted with 3-8 membered heterocyclyl or —NReRf;
• and
• R4 is hydrogen or C1-6 alkyl;
• R5 is hydrogen, C1-6 alkyl, C1-6haloalkyl;
• R6 is hydrogen or C1-6 alkyl;
• or
• R5 and R6 may be taken together with the carbon to which they are attached to form 3-4 membered cycloalkyl or heterocycle ring;
• and
• each of Re and Rf is independently selected from hydrogen and C1-6 alkyl.