Pyruvamide compounds as inhibitors of dust mite group 1 peptidase allergen and their use

A compound selected from compounds of the following formula, and pharmaceutically acceptable salts thereof:

• wherein:
• —R1 is independently —H or —R1A;
• —R1A is saturated aliphatic C1-6alkyl, and is optionally substituted with one or more substituents —RX1;
• —R2 is —H;
• —R3 is independently —H or —R3A;
• —R3A is saturated aliphatic C1-3alkyl;
• —R4 is —R4A;
• —R4A is -Me;
• —R5 is —H;
• —R6 is —H or —R6A;
• —R6A is saturated aliphatic C1-3alkyl;
• —R7 is —H, —R7A, or —R7B;
• —R7A is saturated aliphatic C1-6alkyl;
• —R7B is independently -L7B1-R7BB or —R7BB;
• -L7B1- is saturated aliphatic C1-3alkylene;
• —R7BB is independently —R7BB1, —R7BB2, —R7BB3, or —R7BB4;
• —R7BB1 is independently phenyl or naphthyl, and is optionally substituted with one or more substituents —RX3;
• —R7BB2 is C5-10heteroaryl, and is optionally substituted with one or more substituents —RX3;
• —R7BB3 is C3-7cycloalkyl, and is optionally substituted with one or more substituents —RX2, or is optionally fused to a benzene ring which is optionally substituted with one or more substituents —RX3;
• —R7BB4 is saturated bridged C5-10cycloalkyl, and is optionally substituted with one or more substituents —RX2;
• —R8 is —H;
• —R9 is independently —H or —R9A;
• —R9A is saturated aliphatic C1-4alkyl;
• —R10 is independently —R10A, —R10B, —R10C, or —R10D;
• —R10A is independently phenyl or naphthyl, and is optionally substituted with one or more substituents —RX3;
• —R10B is C5-10heteroaryl, and is optionally substituted with one or more substituents —RX3;
• —R10C is saturated C3-7cycloalkyl, and is optionally substituted with one or more substituents —RX2;
• —R10D is non-aromatic C3-10heterocyclyl, and is optionally substituted with one or more substituents —RX2;
• or —R9 and —R10, taken together with the nitrogen atom and carbon atom to which they are respectively attached, form a non-aromatic C5-7heterocyclic lactam ring, which is optionally substituted with one or more substituents —RX2, or which is optionally fused to a benzene ring which is optionally substituted with one or more substituents —RX3;
• —R11 is independently —H, —R11A, or —R11B;
• —R11A is independently —RZ1, —RZ2, —RZ3, —RZ4, —RZ5, -LZ-RZ2, -LZ-RZ3, -LZ-RZ4, or -LZ-RZ5;
• —RZ1 is saturated aliphatic C1-6alkyl, and is optionally substituted with one or more substituents —RX1;
• each —RZ2 is saturated C3-7cycloalkyl, and is optionally substituted with one or more substituents —RX2;
• each —RZ3 is independently —RZ3A or —RZ3B;
• each —RZ3A is non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more substituents —RX2;
• each —RZ3B is saturated bridged C5-10heterocyclyl, and is optionally substituted with one or more substituents —RX2;
• each —RZ4 is independently phenyl or naphthyl, and is optionally substituted with one or more substituents —RX3;
• each —RZ5 is C5-10heteroaryl, and is optionally substituted with one or more substituents —RX3;
• each -LZ- is saturated aliphatic C1-4alkylene;
• —R11B is —CRJ1RJ2—C(═O)—NRJ3RJ4;
• —RJ1 is independently —H or saturated aliphatic C1-4alkyl;
• —RJ2 is independently —H or saturated aliphatic C1-4alkyl;
• —RJ3 is independently —H, saturated aliphatic C1-4alkyl, phenyl, or benzyl;
• —RJ4 is independently —H, saturated aliphatic C1-4alkyl, phenyl, or benzyl;
• or —NRJ3RJ4 is a C3-10heterocyclyl group, and is optionally substituted with one or more substituents —RX2;
• —R12 is independently —H or —R12A;
• —R12A is saturated aliphatic C1-4alkyl;
• wherein each —RX1 is independently selected from:
• —F, —Cl, —Br, —I, phenyl, —CF3, —OH, —ORS, —OCF3, —NH2, —NHRS, —NRS2, pyrrolidino, piperidino, morpholino, piperizino, N—(C1-4alkyl)-piperizino, —NHC(═O)RS, —NRSC(═O)RS, —C(═O)RS, —C(═O)OH, —C(═O)ORS, —C(═O)NH2, —C(═O)NHRS, —C(═O)NRS2, —C(═O)-pyrrolidino, —C(═O)-piperidino, —C(═O)-morpholino, —C(═O)-piperizino, —C(═O)—{N—(C1-4alkyl)-piperizino}-, —SRS, —S(═O)RS, and —S(═O)2RS;
• wherein each —RS is independently saturated aliphatic C1-6alkyl, phenyl, or —CH2-phenyl;
• wherein each phenyl is optionally substituted with one or more groups selected from:
• —F, —Cl, —Br, —I, —RSS, —CF3, —OH, —ORSS, or —OCF3, wherein each —RSS is saturated aliphatic C1-4alkyl;
• and wherein each —RX2 is independently selected from:
• —F, —Cl, —Br, —I, —RT, phenyl, —OH, —ORT, —C(═O)RT, —NH2, —NHRT, —NRT2, pyrrolidino, piperidino, morpholino, piperizino, N—(C1-4alkyl)-piperizino, —NHC(═O)RT, and —NRTC(═O)RT;
• wherein each —RT is independently saturated aliphatic C1-6alkyl, phenyl, or —CH2-phenyl;
• wherein each phenyl is optionally substituted with one or more groups selected from:
• —F, —Cl, —Br, —I, —RTT, —CF3, —OH, —ORTT, or —OCF3, wherein each —RTT is saturated aliphatic C1-4alkyl,
• and wherein each —RX3 is independently selected from:
• —F, —Cl, —Br, —I,
• —RV,
• —CH═CH2, —C≡CH, cyclopropyl,
• —CF3, —CHF2, —OCF3, —OCHF2,
• —CN,
• —NO2,
• —OH, —ORV,
• -LV-OH, -LV-ORV,
• —O-LV-OH, —O-LV-ORV,
• —NH2, —NHRV, —NRV2,
• pyrrolidino, piperidino, morpholino,
• piperizino, N—(C1-4alkyl)-piperizino,
• -LV-NH2, -LV-NHRV, -LV-NRV2,
• -LV-pyrrolidino, -LV-piperidino, -LV-morpholino,
• -LV-piperizino, -LV-{N—(C1-4alkyl)-piperizino},
• -LV-imidazol-2-yl, -LV-{N—(C1-4alkyl)-imidazol-2-yl},
• —O-LV-NH2, —O-LV-NHRV, —O-LV-NRV2,
• —O-LV-pyrrolidino, —O-LV-piperidino, —O-LV-morpholino,
• —O-LV-piperizino, —O-LV-{N—(C1-4alkyl)-piperizino},
• —O-LV-imidazol-2-yl, —O-LV-{N—(C1-4alkyl)-imidazol-2-yl},
• —NHC(═O)RV, —NRVC(═O)RV,
• —C(═O)RV,
• —C(═O)OH, —C(═O)ORV,
• —C(═O)NH2, —C(═O)NHRV, —C(═O)NRV2,
• —C(═O)-pyrrolidino, —C(═O)-piperidino, —C(═O)-morpholino,
• —C(═O)-piperizino, —C(═O)—{N—(C1-4alkyl)-piperizino}-,
• —NHC(═O)NH2, —NHC(═O)NHRV, —NHC(═O)NRV2,
• —NHC(═O)-pyrrolidino, —NHC(═O)-piperidino, —NHC(═O)-morpholino,
• —NHC(═O)-piperizino, —NHC(═O)—{N—(C1-4alkyl)-piperizino}-,
• —S(═O)2RV,
• —S(═O)2NH2, —S(═O)2NHRV, —S(═O)2NRV2, and
• ═O;
• wherein each -LV- is saturated aliphatic C1-4alkylene;
• wherein each —RV is independently saturated aliphatic C1-6alkyl, phenyl, —CH2-phenyl, C5-6heteroaryl, or —CH2—C5-6heteroaryl;
• wherein each phenyl is optionally substituted with one or more groups selected from:
• —F, —Cl, —Br, —I, —RVV, —CF3, —OH, —ORVV, or —OCF3;
• wherein each C5-6heteroaryl is optionally substituted with one or more groups selected from:
• —F, —Cl, —Br, —I, —RVV, —CF3, —OH, —ORVV, or —OCF3;
• wherein each —RVV is saturated aliphatic C1-4alkyl;
• and additionally, two adjacent groups —RX3 may together form —OCH2O—, —OCH2CH2O—, —CH2OCH2— or —OCH2CH2—;
• and additionally, two adjacent groups —RX3 may, together with the ring atoms to which they are attached, form a C5-7carbocyclic ring or a C5-7heterocyclic ring.