Cysteine protease inhibitors and methods of use thereof

A compound having Formula V:

• or a stereoisomer, tautomer, pharmaceutically acceptable salt, or solvate thereof, wherein:
• R1 is selected from the group consisting of:
• R2a is selected from the group consisting of C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, and —C1-6 alkyl-C3-6 cycloalkyl, wherein the C1-6 alkyl, C2-6 alkenyl, C3-6 cycloalkyl, or —C1-6 alkyl-C3-6 cycloalkyl is independently optionally substituted with one, two, three, or four groups independently selected from the group consisting of halogen, C1-6 alkyl, C1-6 haloalkyl, —OR5, and —N(R5)(R6);
• R3 is selected from the group consisting of:
• R3a, R3b, R3c, and R3d are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• or
• R3a and R3b taken together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl, wherein the 5- or 6-membered heterocycloalkyl is independently optionally substituted with one or two C1-6 alkyl groups;
• and
• R3c and R3d are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• or
• R3b and R3c taken together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl, wherein the 5- or 6-membered heterocycloalkyl is independently optionally substituted with one or two C1-6 alkyl groups;
• and
• R3a and R3d are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• or
• R3c and R3d taken together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl, wherein the 5- or 6-membered heterocycloalkyl is independently optionally substituted with one or two C1-6 alkyl groups;
• and
• R3a and R3b are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• R3e is selected from the group consisting of hydrogen and C1-6 alkyl;
• R3f, R3g, R3h, and R3i are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• or
• R3f and R3g taken together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl, wherein the 5- or 6-membered heterocycloalkyl is independently optionally substituted with one or two C1-6 alkyl groups;
• and
• R3h and R3i are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• or
• R3g and R3h taken together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl, wherein the 5- or 6-membered heterocycloalkyl is independently optionally substituted with one or two C1-6 alkyl groups;
• and
• R3f and R3i are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• or
• R3h and R3i taken together with the carbon atoms to which they are attached form a 5- or 6-membered heterocycloalkyl, wherein the 5- or 6-membered heterocycloalkyl is independently optionally substituted with one or two C1-6 alkyl groups;
• and
• R3f and R3g are independently selected from the group consisting of hydrogen, halogen, cyano, C1-6 alkyl, C1-6 haloalkyl, C3-6 cycloalkyl, —OR5, and —N(R5)(R6);
• R3j is selected from the group consisting of C1-6 alkyl and C1-6 haloalkyl;
• R3k is selected from the group consisting of C1-6 alkyl and C3-6 cycloalkyl;
• R3m is selected from the group consisting of hydrogen and C1-6 alkyl;
• R4a is C1-3 alkyl;
• R4b is selected from the group consisting of hydrogen and C1-3 alkyl;
• or
• R4a and R4b taken together with the nitrogen to which they are attached form a 3- to 8-membered heterocycloalkyl;
• each R5 is independently selected from the group consisting of hydrogen, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-heteroaryl, wherein the C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, or C1-9 heteroaryl are independently optionally substituted with one, two, or three groups independently selected from the group consisting of halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 alkoxy, C3-6 cycloalkyl, C2-9 heterocycloalkyl, C6-10 aryl, and C1-9 heteroaryl;
• each R6 is independently selected from hydrogen, C1-6 alkyl, and C1-6 haloalkyl;
• R7 is selected from the group consisting of —OR7a and —NR7bR7c;
• R7a is selected from the group consisting of hydrogen, C1-6 alkyl, and C3-6 cycloalkyl;
• R7b and R7c are independently selected from the group consisting of hydrogen, C1-6 alkyl, and C3-6 cycloalkyl;
• R8a, R8b, and R8c are independently selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, and —N(R5)(R6);
• and
• R9a, R9b, R9c, and R9d are independently selected from the group consisting of hydrogen, halogen, C1-6 alkyl, C1-6 haloalkyl, —OR5, and —N(R5)(R6).