Peptidomimetic n5-methyl-n2-(nonanoyl-l-leucyl)-l-glutaminate derivatives, triazaspiro[4.14]nonadecane derivatives and similar compounds as inhibitors of norovirus and coronavirus replication

A compound having a structure of Formula (I), or a pharmaceutically acceptable salt thereof:

• wherein
• X is NRN, O, or CR5R6;
• Q is O, NRO, or a bond;
• each RN is independently H or C1-6alkyl;
• each RO is independently H or C1-6alkyl;
• R1 is C1-8alkyl, C1-12alkylene-C6-10aryl, 5- to 12-membered heterocycle having 1 to 3 ring heteroatoms selected from N, O, and S, or C5-8carbocyclyl, and
• the C1-12alkylene is optionally substituted with a C3-5 carbocycle,
• the C6-10aryl is optionally substituted with 1-3 halo,
• the 5- to 12-membered heterocycle is optionally substituted with 1-3 substituents independently selected from COO—C1-6alkyl, C1-6alkylene-C6-10aryl, and SO2—C1-6alkyl, and
• the C5-8carbocyclyl is optionally substituted with C6-10aryl or C6-10aryl substituted with 1-3 halo;
• or
• RO and R1 together with the nitrogen to which they are attached form a 5- to 12-membered heterocycle having 1-3 ring heteroatoms selected from N, O, and S, and optionally substituted with 1-3 halo;
• R2 is C1-6alkyl or C1-6alkylene-C5-8carbocyclyl, wherein C5-8carbocyclyl is optionally substituted with 1-3 substituents independently selected from C1-6alkyl and halo;
• R3 is H or C1-6alkyl;
• R4 is C1-6alkylene-OH, C1-6alkylene-OH substituted with PO(OCH2CH2)2 or SO3H, CHO, C(O)-(4-8 membered heterocycle having 1-3 ring heteroatoms selected from N, O, and S, CONRARB, or C(O)—C(O)NRN—Y1—X1-A, wherein A is C5-8carbocyclyl, 4-12-membered heterocycle having 1-3 ring heteroatoms selected from N, O, and S, C6-10aryl, or 5-8-membered heteroaryl having 1-3 ring heteroatoms selected from N, O, and S, and the carbocyclyl, heterocyclyl, aryl, or heteroaryl is optionally substituted with 1-2 substituents independently selected from halo, C1-6alkyl, and COO—C1-6alkyl;
• Y1 is C1-6alkylene optionally substituted with 1-3 substituents independently selected from halo, OH, NRNRN, and C1-6alkoxy;
• X1 is null, NRNRN, C(O), SO2, or OC(O);
• R5 and R6 are each independently H or C1-6alkyl;
• R7 is C1-6alkyl, C1-6alkylene-O—C1-6alkyl, C1-6alkylene-O—C1-6alkylene-O—C1-6alkyl, C1-6alkylene-CONH—C1-6alkyl, C0-6alkylene-CON(CH3)2, C1-6alkylene-NHCONH—C1-6alkyl, C1-6alkylene-OCONH—C1-6alkyl, C1-6alkylene-NHCOO—C1-6alkyl, C1-6alkylene-NHSO2—C1-6alkyl, C0-6alkylene-C6-10aryl and the C0-6alkylene is optionally substituted with C3-5carbocyclyl, or C1-6alkylene-5-8 membered heteroaryl having 1-3 ring heteroatoms selected from N, O, and S, wherein C6-10aryl and 5-8 membered heteroaryl are optionally substituted with 1-3 substituents independently selected from C1-6alkoxy and halo;
• R8 is H or C1-6alkyl;
• or
• R4 and R8 together with the atoms to which they are attached form a 5- to 8-membered heterocycle having 1-3 ring heteroatoms selected from N, O, and S, optionally substituted with 1-3 RC;
• or
• R6 and R8 together with the atoms to which they are attached form a 5- to 8-membered heterocycle having 1-3 ring heteroatoms selected from N, O, and S, optionally substituted with CN, C1-6alkylene-O—C1-6alkyl, C1-6alkylene-O—C1-6alkylene-O—C1-6alkyl, C0-6alkylene-C6-10aryl, or a 6-membered heterocycle having 1-3 ring heteroatoms selected from N, O, and S, and R7 can be H;
• or
• R7 and R8 together with the nitrogen to which they are attached form a 5-12 membered heterocycle having 1-3 ring heteroatoms selected from N, O, and S, optionally substituted with halo, C6-10aryl, or COO—C1-6 alkyl;
• RA and RB are each independently H, C1-6alkyl, or C1-6alkoxy;
• and
• each RC is independently OH or CONH(C1-6alkyl).