Anti-bacterial compounds based on amino-gold phosphine complexes

A compound of formula (I):

• and pharmaceutically acceptable salts and solvates thereof wherein:
• PX is selected from the group consisting of (P1), (P2) and (P3);
• wherein
• RP1 and RP2 are each independently selected from
• methyl, ethyl, isopropyl and phenyl;
• RP3 is selected from the group consisting of
• methyl and ethyl,
• isopropyl, t-butyl,
• cyclopentyl,
• phenyl,
• 4-membered or 5-membered heterocycloalkyl group linked to phosphorus via a carbon atom in the ring, including a single heteroatom independently selected from NRZ, O and S,
• —CF3, —CH2CF3—CH2CF2H, —CH2CH2ORPB,
• —CH2Q and —(CHZ)Q;
• wherein Q is a C5-6 heteroaryl group, optionally substituted with one or more groups RPA;
• RP4 is selected from methyl and ethyl;
• m is an integer selected from 1, 2 or 3;
• RM is one or more optional substituents on the ring independently selected from
• RPC when attached to a carbon atom adjacent the phosphorus atom, or
• —OH, —OC1-3alkyl and RPC, when attached to other ring carbons;
• -LB- is methylene, ethylene or is absent;
• when -LB- is present, RP4 is absent and R1 is selected from N, CH and CRPC;
• when -LB- is absent, R1 is selected from the group consisting of
• O,
• NRZ,
• SO2,
• CH2, CHF, CF2 and CHRPC;
• wherein RZ is selected from the group consisting of
• H, C1-3alkyl, COC1-3alkyl and SOC1-3alkyl;
• R5 and R8 are each independently selected from H and RPC;
• R6 and R7 are each independently selected from H and RPC;
• wherein RPC is selected from the group consisting of
• C1-3alkyl optionally substituted with one or more groups RPD;
• wherein RPA is selected from the group consisting of
• linear or branched C1-6alkyl, C1-6alkenyl or C2-6alkynyl optionally substituted with one or more groups RAL,
• —F, —Cl, —Br, —CN
• —OH, —ORPE,
• —CF3—CF2H,
• —CORPE,
• —CH2OH, —CH2ORPE,
• —COOH, —COORPE, —CONH2, —CONHRPE, —CONRPE2,
• —OCORPE, —OCONH2, —OCONHRPE, —OCONRPE2,
• —NH2, —NHRPE, —NRPE2,
• —SO2NH2, —SO2NHRPE2, —SO2NRPE2,
• —SO2RPE,
• —NHCOH, —NHCORPE, —NRPECOH and —NRPECORPE;
• and RPB is selected from the group consisting of
• linear or branched C1-6alkyl, C2-6alkenyl or C2-6alkynyl optionally substituted with one or more groups RAT,
• C3-6cycloalkyl, C4-6heterocycloalkyl, C5-6cycloalkenyl or C5-6heterocycloalkenyl optionally substituted with one or more groups RAT,
• phenyl optionally substituted with one or more groups RAR, and
• C5-6heteroaryl optionally substituted with one or more groups RAR;
• RPE is selected from
• linear or branched C1-4alkyl optionally substituted with one or more groups RPD;
• and RPD is selected from the group consisting of
• F,
• OH and OC1-3alkyl;
• RA is selected from the group consisting of
• H;
• linear or branched C1-6alkyl, C2-6alkenyl, C2-6alkynyl, C3-6cycloalkyl, C4-6heterocycloalkyl, C5-6cycloalkenyl and C5-6heterocycloalkenyl optionally substituted with one or more groups RAL,
• C5-6heteroaryl, optionally substituted with one or more groups RA1,
• C1-3alkyl substituted by phenyl or C5-6heteroaryl, which groups may optionally substituted with one or more groups RA1,
• RB is selected from —CORA2 and —SORA2;
• or RA and RB together with the nitrogen atom to which they are attached form
• a 5- or 6-membered heteroaryl, heterocycloalkyl or heterocycloalkenyl group optionally substituted with one or more groups selected from
• oxo,
• ═NH;
• phenyl optionally substituted with one or more groups RA1,
• RA2, and
• RA1;
• an 8- to 10-membered heterobicyclyl group optionally substituted with one or more groups selected from
• oxo,
• —NO2;
• —C(═O)N(RN1)2, wherein each RN1 is independently selected from RN2 and —ORN3, wherein RN2 and RN3 are each independently selected from linear unsubstituted C1-6alkyl;
• phenyl optionally substituted with one or more groups RA1,
• RA2 and
• RA1;
• with the proviso that when PX is P(C2H5)3, —NRARB is not selected from the groups (X1) or (X6)
• with the further proviso that when PX is PPh3, —NRARB is not selected from the groups (X15):
• (X15)
• wherein
• RA1 is selected from the group consisting of
• linear or branched C1-6alkyl, C2-6alkenyl or C2-6alkynyl optionally substituted with one or more groups RAL,
• —F, —Cl, —Br, —CN
• —OH, —ORA2,
• —CF3—CF2H,
• —CORA2,
• —CH2OH, —CH2ORA2, —CHRA2OH, CHRA2ORA2
• —COOH, —COORA2, —CONH2, —CONHRA2, —CONRA22,
• —OCORA2, —OCONH2, —OCONHRA2, —OCONRA22,
• —NH2, —NHR2, —NRA22,
• —SO2NH2, —SO2NHRA22, —SO2NRA22,
• —SO2RA2,
• —NHCOH, —NHCORA2, —NRA2COH and —NRA2CORA2;
• RA2 is selected from the group consisting of
• linear or branched C1-6alkyl, C2-6alkenyl or C2-6alkynyl optionally substituted with one or more groups RAT,
• C3-6cycloalkyl C4-6heterocycloalkyl C5-6cycloalkenyl or C5-6heterocycloalkenyl optionally substituted with one or more groups RAT,
• phenyl optionally substituted with one or more groups RAR, and
• C5-10heteroaryl optionally substituted with one or more groups RAR;
• where N is substituted by 2 RA2 groups, the N and the RA2 groups may together form a N-containing C5-6 heterocycloalkyl group;
• RAL is selected from the group consisting of
• linear or branched C1-6alkyl optionally substituted with one or more groups RAT;
• —F, —CN
• —OH, —ORA2,
• —CF3, —CF2H,
• —CORA2,
• —COOH, —COORA2, —CONH2, —CONHRA2, —CONRA22,
• —OCORA2, —OCONH2, —OCONHRA2, —OCONRA22,
• —NH2, —NHRA2, —NRA22,
• —SO2NH2, —SO2NHRA22, —SO2NRA22,
• —SO2RA2,
• —NHCOH, —NHCORA2, —NRA2COH and —NRA2CORA2;
• and
• wherein RAR is selected from the group consisting of
• linear or branched C1-6alkyl, C2-6alkenyl or C2-6alkynyl optionally substituted with one or more groups RAL,
• —F, —Cl, —Br, —CN
• —OH, —OR1A1,
• —CF3, —CF2H,
• —COR1A1,
• —CH2OH, —CHOR1A1, —CHR1A1OH, CHR1A1OR1A1
• —COOH, —COOR1A1, —CONH2, —CONHR1A1, —CONR1A12,
• —OCOR1A1, —OCONH2, —OCONHR1A1, —OCONR1A12,
• —NH2, —NHR1A1, —NR1A12,
• —SO2NH2, —SO2NHR1A12, —SO2NR1A12,
• —SO2R1A1,
• —NHCOH, —NHCOR1A1, —NR1A1COH and —NR1A1COR1A1;
• RAT is selected from the group consisting of
• —F, —CN
• —OH, —OC1-3alkyl,
• —CF3, —CF2H,
• —COC1-3alkyl,
• —COOH, —COOC1-3alkyl, —CONH2, —CONHC1-3alkyl, —CON(C1-3alkyl)2,
• —OCOC1-3alkyl, —OCONH2, —OCONHC1-3alkyl, —OCON(C1-3alkyl)2,
• —NH2, —NHC1-3alkyl, —N(C1-3alkyl)2,
• —SO2NH2, —SO2NH(C1-3alkyl)2, —SO2N(C1-3alkyl)2,
• —SO2(C1-3alkyl),
• —NHCOH, —NHCO(C1-3alkyl), —N(C1-3alkyl)COH and —N(C1-3alkyl)CO(C1-3alkyl);
• with the provisos that when PX is P(CH3)3, —NRARB is not selected from any of the groups (X1) to (X5), (X7) and (X12) to (X15);
• and when PX is P(C2H5)3, —NRARB is not selected from the groups (X1), (X6) to (X11), (X13) and (X14);
• and when PX is PPh3, —NRARB is not selected from the groups (X2), (X12), (X14) and (X15):