2-amino-N-(amino-oxo-aryl-lambda6-sulfanylidene)acetamide compounds and their therapeutic use

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

• wherein:
• -A is independently -AC or -AH;
• -AC is independently phenyl or naphthyl, and is optionally substituted with one or more substituents —RX;
• -AH is independently C5-12heteroaryl, and is optionally substituted with one or more substituents —RX;
• and wherein:
• each —RX is independently selected from:
• —RXX, —RXXU, —RXXV,
• —F, —Cl, —Br, —I,
• —OH, —ORXX,
• -LXX-OH, -LXX-ORXX,
• —CF3, —CHF2, —OCF3, —OCHF2,
• —NH2, —NHRXX, —NRXX2, —RXM,
• -LXX-NH2, -LXX-NHRXX, -LXX-NRXX2, -LXX-RXM,
• —C(═O)OH, —C(═O)ORXX, —OC(═O)RXX,
• —C(═O)NH2, —C(═O)NHRXX, —C(═O)NRXX2, —C(═O)RXM,
• —NHC(═O)RXX, —NRXNC(═O)RXX,
• —NHC(═O)NH2, —NHC(═O)NHRXX, —NHC(═O)NRXX2, —NHC(═O)RXM,
• —NRXNC(═O)NH2, —NRXNC(═O)NHRXX, —NRXNC(═O)NRXX2, —NRXNC(═O)RXM,
• —NHC(═O)ORXX, —NRXNC(═O)ORXX,
• —OC(═O)NH2, —OC(═O)NHRXX, —OC(═O)NRXX2, —OC(═O)RXM,
• —NHC(═NH)NH2,
• —C(═O)RXX,
• —S(═O)NH2, —S(═O)NHRXX, —S(═O)NRXX2, —S(═O)RXM,
• —S(═O)2NH2, —S(═O)2NHRXX, —S(═O)2NRXX2, —S(═O)2RXM,
• —NHS(═O)RXX, —NRXNS(═O)RXX,
• —NHS(═O)2RXX, —NRXNS(═O)2RXX,
• —S(═O)RXX, —S(═O)2RXX,
• —SH, —SRXX, —CN, and —NO2;
• and additionally, two adjacent groups —RX, if present, may together form:
• —O—CH2—O—, —O—CH2CH2—O—, —CH2—CH2—O—, —CH2—CH2CH2—O—,
• —CH2—O—CH2—, or —CH2—CH2—O—CH2—;
• wherein:
• each -LXX- is linear or branched saturated C1-4alkylene;
• each —RXX is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• each —RXXU is independently linear or branched C2-4alkenyl;
• each —RXXV is independently linear or branched C2-4alkynyl;
• each —RXN is linear or branched saturated C1-4alkyl;
• each —RXM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
• optionally substituted with one or more groups selected from:
• —RXMM, —C(═O)RXMM, —C(═O)ORXMM, and —S(═O)2RXMM;
• wherein each —RXMM is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• —R1 is independently —H or —R11;
• —R11 is independently —R11A or —R11B;
• —R11A is independently:
• —RA1, —RA2, —RA3, —RA4, —RA5, -LA-RA2, -LA-RA3, -LA-RA4, or -LA-RA5;
• each —RA1 is linear or branched saturated C1-6alkyl, and is optionally substituted with one or more groups —RAA2;
• each —RA2 is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups —RAA1 and one or more groups —RAA2;
• each —RA3 is non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups —RAA1 and one or more groups —RAA2;
• each —RA4 is independently phenyl or naphthyl, and is optionally substituted with one or more groups —RAA1 and one or more groups —RAA2;
• each —RA5 is C5-10heteroaryl, and is optionally substituted with one or more groups —RAA1 and one or more groups —RAA2;
• each -LA- is linear or branched saturated C1-4alkylene;
• each —RAA1 is independently selected from:
• —RAA,
• -LAA-OH, -LAA-ORAA,
• -LAA-NH2, -LAA-NHRAA, -LAA-N(RAA)2, and -LAA-RAM;
• each —RAA2 is independently selected from:
• —F, —Cl, —Br, —I,
• —OH, —ORAA,
• —CF3, —CHF2, —OCF3, —OCHF2,
• —NH2, —NHRAA, —N(RAA)2, —RAM,
• —C(═O)OH, —C(═O)ORAA, —OC(═O)RAA,
• —C(═O)NH2, —C(═O)NHRAA, —C(═O)N(RAA)2, —C(═O)RAM,
• —NHC(═O)RAA, —NRANC(═O)RAA,
• —NHC(═O)NH2, —NHC(═O)NHRAA, —NHC(═O)N(RAA)2, —NHC(═O)RAM,
• —NRANC(═O)NH2, —NRANC(═O)NHRAA, —NRANC(═O)N(RAA)2, —NRANC(═O)RAM,
• —NHC(═O)ORAA, —NRANC(═O)ORAA,
• —OC(═O)NH2, —OC(═O)NHRAA, —OC(═O)N(RAA)2, —OC(═O)RAM,
• —NHC(═NH)NH2,
• —C(═O)RAA,
• —S(═O)NH2, —S(═O)NHRAA, —S(═O)N(RAA)2, —S(═O)RAM,
• —S(═O)2NH2, —S(═O)2NHRAA, —S(═O)2N(RAA)2, —S(═O)2RAM,
• —NHS(═O)RAA, —NRANS(═O)RAA,
• —NHS(═O)2RAA, —NRANS(═O)2RAA,
• —S(═O)RAA, —S(═O)2RAA,
• —SH, —SRAA, —CN, and —NO2;
• wherein:
• each -LAA- is linear or branched saturated C1-4alkylene;
• each —RAA is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• each —RAN is linear or branched saturated C1-4alkyl;
• each —RAM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
• optionally substituted with one or more groups selected from:
• —RAMM, —C(═O)RAMM, —C(═O)ORAMM, and —S(═O)2RAMM;
• wherein each —RAMM is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• —R11B is independently selected from:
• —F, —Cl, —Br, —I,
• —OH, —ORBB,
• —CF3, —CHF2, —OCF3, —OCHF2,
• —NH2, —NHRBB, —NRBB2, —RBM,
• —C(═O)OH, —C(═O)ORBB, —OC(═O)RBB,
• —C(═O)NH2, —C(═O)NHRBB, —C(═O)NRBB2, —C(═O)RBM,
• —NHC(═O)RBB, —NRBNC(═O)RBB,
• —NHC(═O)NH2, —NHC(═O)NHRBB, —NHC(═O)NRBB2, —NHC(═O)RBM,
• —NRBNC(═O)NH2, —NRBNC(═O)NHRBB, —NRBNC(═O)NRBB2, —NRBNC(═O)RBM,
• —NHC(═O)ORBB, —NRBNC(═O)ORBB,
• —OC(═O)NH2, —OC(═O)NHRBB, —OC(═O)NRBB2, —OC(═O)RBM,
• —NHC(═NH)NH2,
• —C(═O)RBB,
• —S(═O)NH2, —S(═O)NHRBB, —S(═O)NRBB2, —S(═O)RBM,
• —S(═O)2NH2, —S(═O)2NHRBB, —S(═O)2NRBB2, —S(═O)2RBM,
• —NHS(═O)RBB, —NRBNS(═O)RBB,
• —NHS(═O)2RBB, —NRBNS(═O)2RBB,
• —S(═O)RBB, —S(═O)2RBB,
• —SH, —SRBB, —CN, and —NO2;
• wherein:
• each —RBB is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• each —RBN is linear or branched saturated C1-4alkyl;
• each —RBM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
• optionally substituted with one or more groups selected from:
• —RBMM, —C(═O)RBMM, —C(═O)ORBMM, and —S(═O)2RBMM;
• wherein each —RBMM is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• —R2 is independently —H or —R22;
• —R22 is independently —R22C or —R22D;
• —R22C is independently:
• —RC1, —RC2, —RC3, —RC4, —RC5, -LC-RC2, -LC-RC3, -LC-RC4, or -LC-RC5;
• each —RC1 is linear or branched saturated C1-6alkyl, and is optionally substituted with one or more groups —RCC2;
• each —RC2 is saturated C3-6cycloalkyl, and is optionally substituted with one or more groups —RCC1 and one or more groups —RCC2;
• each —RC3 is non-aromatic C3-6heterocyclyl, and is optionally substituted with one or more groups —RCC1 and one or more groups —RCC2;
• each —RC4 is independently phenyl or naphthyl, and is optionally substituted with one or more groups —RCC1 and one or more groups —RCC2;
• each —RC5 is C5-10heteroaryl, and is optionally substituted with one or more groups —RCC1 and one or more groups —RCC2;
• each -LC- is linear or branched saturated C1-4alkylene;
• each —RCC1 is independently selected from:
• —RCC,
• -LCC-OH, -LCC-ORCC,
• -LCC-NH2, -LCC-NHRCC, -LCC-N(RCC)2, and -LCC-RCM;
• each —RCC2 is independently selected from:
• —F, —Cl, —Br, —I,
• —OH, —ORCC,
• —CF3, —CHF2, —OCF3, —OCHF2,
• —NH2, —NHRCC, —N(RCC)2, —RCM,
• —C(═O)OH, —C(═O)ORCC, —OC(═O)RCC,
• —C(═O)NH2, —C(═O)NHRCC, —C(═O)N(RCC)2, —C(═O)RCM,
• —NHC(═O)RCC, —NRCNC(═O)RCC,
• —NHC(═O)NH2, —NHC(═O)NHRCC, —NHC(═O)N(RCC)2, —NHC(═O)RCM,
• —NRCNC(═O)NH2, —NRCNC(═O)NHRCC, —NRCNC(═O)N(RCC)2,
• —NRCNC(═O)RCM,
• —NHC(═O)ORCC, —NRCNC(═O)ORCC,
• —OC(═O)NH2, —OC(═O)NHRCC, —OC(═O)N(RCC)2, —OC(═O)RCM,
• —NHC(═NH)NH2,
• —C(═O) RCC,
• —S(═O)NH2, —S(═O)NHRCC, —S(═O)N(RCC)2, —S(═O)RCM,
• —S(═O)2NH2, —S(═O)2NHRCC, —S(═O)2N(RCC)2, —S(═O)2RCM,
• —NHS(═O)RCC, —NRCNS(═O)RCC,
• —NHS(═O)2RCC, —NRCNS(═O)2RCC,
• —S(═O)RCC, —S(═O)2RCC,
• —SH, —SRCC, —CN, and —NO2;
• wherein:
• each -LCC- is linear or branched saturated C1-4alkylene;
• each —RCC is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• each —RCN is linear or branched saturated C1-4alkyl;
• each —RCM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
• optionally substituted with one or more groups selected from:
• —RCMM, —C(═O)RCMM, —C(═O)ORCMM, and —S(═O)2RCMM;
• wherein each —RCMM is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• —R22D is independently selected from:
• —F, —Cl, —Br, —I,
• —OH, —ORDD,
• —CF3, —CHF2, —OCF3, —OCHF2,
• —NH2, —NHRDD, —NRDD2, —RDM,
• —C(═O)OH, —C(═O)ORDD, —OC(═O)RDD,
• —C(═O)NH2, —C(═O)NHRDD, —C(═O)NRDD2, —C(═O)RDM,
• —NHC(═O)RDD, —NRDNC(═O)RDD,
• —NHC(═O)NH2, —NHC(═O)NHRDD, —NHC(═O)NRDD2, —NHC(═O)RDM,
• —NRDNC(═O)NH2, —NRDNC(═O)NHRDD, —NRDNC(═O)NRDD2, —NRDNC(═O)RDM,
• —NHC(═O)ORDD, —NRDNC(═O)ORDD,
• —OC(═O)NH2, —OC(═O)NHRDD, —OC(═O)NRDD2, —OC(═O)RDM,
• —NHC(═NH)NH2,
• —C(═O)RDD,
• —S(═O)NH2, —S(═O)NHRDD, —S(═O)NRDD2, —S(═O)RDM,
• —S(═O)2NH2, —S(═O)2NHRDD, —S(═O)2NRDD2, —S(═O)2RDM,
• —NHS(═O)RDD, —NRDNS(═O)RDD,
• —NHS(═O)2RDD, —NRDNS(═O)2RDD,
• —S(═O)RDD, —S(═O)2RDD,
• —SH, —SRDD, —CN, and —NO2;
• wherein:
• each —RDD is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• each —RDN is linear or branched saturated C1-4alkyl;
• each —RDM is independently azetidino, pyrrolidino, piperidino, piperazino, morpholino, azepano, or diazepano, and is:
• optionally substituted with one or more groups selected from:
• —RDMM, —C(═O)RDMM, —C(═O)ORDMM, and —S(═O)2RDMM;
• wherein each —RDMM is independently linear or branched saturated C1-4alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• or —R1 and —R2, together with the carbon atom to which they are attached, form a saturated C3-6cycloalkyl or a non-aromatic C3-7heterocyclyl, and is optionally substituted with one or more groups —RCC2;
• and wherein:
• —RN1 is independently —H or —RN;
• —RN2 is independently —H or —RN;
• each —RN is independently linear or branched saturated C1-6alkyl, phenyl, or —CH2-phenyl, wherein each phenyl is optionally substituted with one or more groups selected from —F, —Cl, —Br, -Me, —OH, —OMe, —CF3, and —OCF3;
• or
• —RN1 and RN2, taken together, form C2-6alkylene.