Pyrrol derivatives with antibacterial activity

A compound of the formula (1) or a pharmaceutically acceptable salt thereof:

• wherein:
• W is O or NR5;
• Y is hydrogen;
• R1 is selected from R1a, R1b, R1c, R1d, R1e and R1f;
• R1a is a 4 to 7 membered saturated, partially unsaturated or unsaturated heterocyclic ring containing 1, 2, 3, or 4 heteroatoms independently selected from O, S and N (provided that such a ring does not contain O—O or S—S bonds), wherein a —CH2— group can optionally be replaced by a —C(O)—, a ring sulphur atom may be optionally oxidised to form the S-oxide(s), and a ring nitrogen atom may be optionally oxidised to form the N-oxide, and wherein said ring may be optionally substituted by 1, 2 or 3 substituents independently selected from:
• nitro, cyano, sulfo, formyl, hydroxyiminomethyl, (2-6C)alkenyl, (2-6C)alkynyl, —CO(1-6C)alkyl, —COO(1-6C)alkyl (optionally substituted with —COO(1-6C)alkyl), trifluoromethyl, —CONR6R7, —OCONR6R7, —N(R7)COR6, —CONHCH(CO2R7)R6, halo, hydroxy, carboxy, (1-6C)alkyl [optionally substituted by 1 or 2 substituents independently selected from hydroxy, halo, cyano, nitro, —COO(1-6C)alkyl, —OCO(1-4C)alkyl, (1-6C)alkoxy, (1-4C)alkoxy(1-4C)alkoxy, hydroxy(1-4C)alkoxy-, (2-4C)alkenyloxy, trifluoromethyl, —CONR6R7, carboxy, —NHC(O)O(1-4C)alkyl, —OCONR6R7, —C(═NOH)(1-4C)alkyl, —C(═NOH)NR6R7, —NHC(═NH)NR5R7, —NHC(O)NR6R7, —NHC(O)(1-4C)alkyl, —NHC(O)heterocyclyl, —NHC(O)aryl, —NHS(O)p(1-4C)alkyl, —S(O)p(1-4C)alkyl, —S(O)pNR6R7, —NHSO2R6, —NR5R7, and heterocyclyl], (3-6C)cycloalkyl (optionally substituted by 1 or 2 substituents selected from (1-6C)alkyl and the optional substituents described for (1-6C)alkyl hereinbefore), —O(1-6C)alkyl (optionally substituted by 1 or 2 substituents as described for (1-6C)alkyl hereinbefore), —S(O)p(1-4C)alkyl (optionally substituted by 1 or 2 substituents as described for (1-6C)alkyl hereinbefore), heterocyclyl, aryl, —NHC(O)O(1-4C)alkyl, —C(═NOR7)(1-4C)alkyl, —C(═NOR7)NR6R7, —S(O)pNR6R7, —S(O)p(1-4C)alkylCONHR7, —NR7S(O)pNR6R7, —NR7S(O)p(1-4C)alkyl, —NR7S(O)p-aryl, —C(O)NHS(O)p(1-4C)alkyl, —C(O)NHS(O)p-aryl, —NR6R7, —CH2CH(CO2R6)OH, -(1-4C)alkylCH(NR6R7)CO2R6 and -(1-4C)alkylCH(NR6R7)CO(NR6R7);
• wherein any aryl or heterocyclyl group in any of the preceding values for substituents on R1a may optionally be substituted by 1 or 2 substituents independently selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, hydroxy, (1-4C)alkoxy, halo, cyano, nitro, carboxy, hydroxy(1-4C)alkyl-, (1-4C)alkoxy(1-4C)alkyl-, halo(1-4C)alkyl-, difluoromethyl, trifluoromethyl, trifluoromethoxy, formyl, —CO(1-4C)alkyl, —COO(1-4C)alkyl, —C(O)NH2, —C(O)NH(1-4C)alkyl, —C(O)N[di(1-4C)alkyl], —S(O)2NH2, —S(O)2NH(1-4C)alkyl and —S(O)2N[di(1-4C)alkyl];
• R1b is an 8-10 membered bicyclic heterocyclic ring containing 1, 2, 3, or 4 heteroatoms independently selected from O, S and N (provided that such a ring does not contain O—O or S—S bonds), wherein a —CH2— group can optionally be replaced by a —C(O)—, a ring sulphur atom may be optionally oxidised to form the S-oxide(s), and a ring nitrogen atom may be optionally oxidised to form the N-oxide, and wherein said ring may be optionally substituted by 1, 2 or 3 substituents independently selected from the substituents listed for R1a above;
• R1c is a phenyl ring, substituted by 1, 2 or 3 substituents independently selected from the substituents listed for R1a above;
• R1d is selected from —CH2R1a, —C(O)R1a, —OR1a, S(O)qR1a (wherein q is 1 or 2);
• R1e is selected from —CH2R1b, —C(O)R1b, —OR1b, S(O)qR1b (wherein q is 1 or 2);
• R1f is selected from —CH2R1c, —C(O)R1c —OR1c, S(O)qR1c (wherein q is 1 or 2);
• R2 is selected from hydrogen, (1-4C)alkyl, cyclopropyl, (2-4C)alkenyl, (2-4C)alkynyl, halo, cyano, fluoromethyl, difluoromethyl and trifluoromethyl;
• R3 is selected from hydrogen, (1-4C)alkyl, cyclopropyl, (2-4C)alkenyl, (2-4C)alkynyl, halo, hydroxy, cyano, fluoromethyl, difluoromethyl trifluoromethyl, —CO(1-6C)alkyl, and (1-6C)alkoxy;
• R4 is selected from hydrogen, (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, nitro, hydroxy, halo, cyano, (3-6C)cycloalkyl, -(1-6C)alkyl(3-6C)cycloalkyl, halo(1-4C)alkyl-, difluoromethyl, trifluoromethyl, —CO(1-6C)alkyl, and (1-6C)alkoxy;
• R6 is independently at each occurrence selected from hydrogen, (1-4C)alkyl, (3-4C)alkenyl, (3-6C)cycloalkyl, -(1-4C)alkylC(O)O(1-4C)alkyl, hydroxy, amino, —NH(1-4C)alkyl, —N[di(1-4C)alkyl], (1-4C)alkoxy, (1-4C)alkoxy(1-4C)alkoxy, (1-4C)alkoxy(1-4C)alkoxy(1-4C)alkoxy, (1-4C)alkoxy(1-4C)alkyl-, (1-4C)alkylthio(1-4C)alkyl-, hydroxy(1-4C)alkyl-, -(1-4C)alkylNH2, -(1-4C)alkylNH(1-4C)alkyl, -(1-4C)alkylN[di(1-4C)alkyl], and -(1-4C)alkylheterocyclyl;
• R7 is independently at each occurrence selected from hydrogen and (1-6C)alkyl;
• or R6 and R7 may together with the nitrogen to which they are attached form a 5 or 6-membered heterocyclyl ring, optionally substituted with 1 or 2 substituents independently selected from (1-4C)alkyl, (2-4C)alkenyl, (2-4C)alkynyl, hydroxy, (1-4C)alkoxy, halo, cyano, nitro, carboxy, hydroxy(1-4C)alkyl-, (1-4C)alkoxy(1-4C)alkyl-, halo(1-4C)alkyl-, difluoromethyl, trifluoromethyl, trifluoromethoxy, formyl, —CO(1-4C)alkyl, —COO(1-4C)alkyl, —C(O)NH2, —C(O)NH(1-4C)alkyl, —C(O)N[di(1-4C)alkyl], —S(O)2NH2, —S(O)2NH(1-4C)alkyl, —S(O)2N[di(1-4C)alkyl] and —S(O)p(1-4C)alkyl;
• R5 is selected from hydrogen and (1-4C)alkyl;
• p is (independently at each occurrence) 0, 1 or 2.