Quinoline derivatives and their use as antibacterial agents

A compound of formula (I):

• wherein:
• one of Z1, Z2, Z3, Z4 and Z5 is CR1a and the remainder are CH, or one of Z1, Z2, and Z3 is N and the remainder are CH;
• R1 is selected from hydroxy;
• (C1-6) alkoxy optionally substituted by (C1-6)alkoxy, amino, piperidyl, guanidino or amidino optionally N-substituted by one or two (C1-6)alkyl, acyl or (C1-6)alkylsulphonyl groups, NH2CO, hydroxy, thiol, (C1-6)alkylthio, heterocyclylthio, heterocyclyloxy, arylthio, aryloxy, acylthio, acyloxy or (C1-6)alkylsulphonyloxy;
• (C1-6)alkoxy-substituted (C1-6)alkyl;
• halogen;
• (C1-6)alkyl;
• (C1-6)alkylthio;
• nitro;
• trifluoromethyl;
• azido;
• acyl;
• acyloxy;
• acylthio;
• (C1-6)alkylsulphonyl;
• (C1-6)alkylsulphoxide;
• arylsulphonyl;
• arylsulphoxide or an amino, piperdyl, guanidino or amidino group optionally N-substituted by one or two (C1-6)alkyl, acyl or (C1-6)alkylsulphonyl groups, wherein acyl is selected from (C1-6)alkoxycarbonyl, formyl and (C1-6)alkylcarbonyl, or when one of Z1, Z2, and Z3 is N, R1 may instead be hydrogen;
• R1a is selected from hydrogen and the groups listed above for R1;
• either R2 is hydrogen;
• and
• R3 is in the 2- or 3-position and is hydrogen or (C1-6)alkyl or (C2-6)alkenyl optionally substituted with 1 to 3 groups selected from:
• thiol;
• halogen;
• (C1-6)alkylthio;
• trifluoromethyl;
• azido;
• (C1-6)alkoxycarbonyl;
• (C1-6)alkylcarbonyl;
• (C2-6)alkenyloxycarbonyl;
• (C2-6)alkenylcarbonyl;
• hydroxy optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylcarbonyl or (C2-6)alkenylcarbonyl;
• amino optionally mono- or disubstituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, (C2-6)alkenylsulphonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
• aminocarbonyl wherein the amino group is optionally mono- or disubstituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl or (C2-6)alkenylcarbonyl;
• oxo;
• (C1-6)alkylsulphonyl;
• (C2-6)alkenylsulphonyl;
• or (C1-6)aminosulphonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
• or when R3 is in the 2-position it may with R4 form a C3-5 alkylene group optionally substituted by a group R5 selected from:
• (C3-12)alkyl;
• hydroxy(C3-12)alkyl;
• (C1-12)alkoxy(C3-12)alkyl;
• (C1-12)alkanoyloxy(C3-12)alkyl;
• (C3-6)cycloalkyl(C3-12)alkyl;
• hydroxy-, (C1-12)alkoxy- or (C1-12)alkanoyloxy-(C3-6)cycloalkyl(C3-12)alkyl;
• cyano(C3-12)alkyl;
• (C2-12)alkenyl;
• (C2-12)alkynyl;
• tetrahydrofuryl;
• mono- or di-(C1-12)alkylamino(C3-12)alkyl;
• acylamino(C3-12)alkyl;
• (C1-12)alkyl- or acylaminocarbonyl(C3-12)alkyl;
• mono- or di- (C1-12)alkylamino(hydroxy)(C3-12)alkyl;
• optionally substituted phenyl(C1-2)alkyl, phenoxy(C1-2)alkyl or phenyl(hydroxy)(C1-2)alkyl;
• optionally substituted diphenyl(C1-2)alkyl;
• optionally substituted phenyl(C2-3)alkenyl;
• optionally substituted benzoyl or benzoylmethyl;
• optionally substituted heteroaryl(C1-2)alkyl;
• and optionally substituted heteroaroyl or heteroaroylmethyl, wherein acyl is selected from (C1-6)alkoxycarbonyl, formyl and (C1-6)alkylcarbonyl;
• or R3 is in the 3-position and R2 and R3 together are a divalent residue ═CR51R61 where R51 and R61 are independently selected from H, (C1-6)alkyl, (C2-6)alkenyl, aryl(C1-6)alkyl and aryl(C2-6)alkenyl, any alkyl or alkenyl moiety being optionally substituted by 1 to 3 groups selected from those listed above for substituents on R3;
• R4 forms a group with R3 as above defined or is a group —CH2—R5 in which R5 is as defined above;
• n is 0, 1 or 2;
• and
• A is NHC(O)NH or NHC(O)O;
• an N-oxide of a compound of formula (I), or a pharmaceutically acceptable salt of a compound of formula (I) or its N-oxide.