Cephalosporin for treating beta-lactam antibiotic resistant bacteria (such as S. aureus, E. faecium or E. faecalis) or PBP2a-producing bacteria

摘要

A compound of Formula (I) wherein the compound is useful in the treatment against methicillin-resistant, vancomycin-resistant or ampicillin-resistant bacteria bacterial infection. The compound of Formula (III) shows one of the preferred compounds. Wherein; R1 is selected from the group consisting of -NHC(O)ZR3, -NR4R5 and Formula (II); wherein Z is selected from the group consisting of -CH2(X)m-, -C(NOR6)-, -CH(OR7)-, -C(CHCO2R8)- and -CH(NR9R10)-; X is selected from oxygen and sulphur; m is 0 or 1; R3 is selected from the group consisting of cyano, C1-6alkyl which may be substituted with one or more substituents selected from the group consisting of hydroxyl, bromo, fluoro, chloro, iodo, mercapto or thio, cyano, C1-6alkylthio, heterocycle selected from the group comprising furyl, thienyl, imidazolyl, indolyl, pyridinyl, thiadiazolyl, thiazolyl, piperazinyl, dibenzfuranyl and dibenzthienyl, C6-14aryl, heteroaryl, carboxyl, C1-6alkoxycarbonyl, C1-6alkyl, C1-6alkenyl, nitro, amino, C1-6alkoxyl and amido; C6-14aryl which may be substituted with one or more substituents selected from the group consisting of hydroxyl, bromo, fluoro, chloro, iodo, mercapto or thio, cyano, cyanoamido, C1-6alkylthio, heterocycle selected from the group comprising furyl, thienyl, imidazolyl, indolyl, pyridinyl, thiadiazolyl, thiazolyl, piperazinyl, dibenzfuranyl and dibenzthienyl, C6-14aryl, heteroaryl, carboxyl, C1-6alkoxycarbonyl, C1-6alkyl, C1-6alkenyl, nitro, amino, C1-6alkoxyl and amido; a heterocycle selected from the group comprising furyl, thienyl, imidazolyl, indolyl, pyridinyl, thiadiazolyl, thiazolyl, piperazinyl, dibenzfuranyl and dibenzthienyl which may be substituted with one or more substituents selected from the group consisting of hydroxyl, bromo, fluoro, chloro, iodo, mercapto or thio, cyano, cyanoamido, C1-6alkylthio, heterocycle, C6-14aryl, heteroaryl, carboxyl, oxo, C1-6alkoxycarbonyl, C1-6alkyl, C1-6alkenyl, nitro, amino, C1-6alkoxyl and amido; or a heteroalkyl group (RHetAr wherein R is C1-6alkyl, HetAr is an aromatic heterocycle), and (CH2)nT, n is 1 to 6, T is selected from the group consisting of amino (NRR' wherein R and R' may be C1-6alkyl, C6-14aryl or acyl C(O)R wherein R is C1-6alkyl), amidino (C- or N-linked), guanidino, and isothioureido, which may be substituted with C1-6alkyl, C6-14aryl, hydroxyl, or amino; R4-7 are independently selected from the group of hydrogen, C1-6alkyl, C6-14aryl and acyl; wherein R6 may also be a group that forms a protected hydroxy group with the adjacent oxygen; R8 is selected from the group of hydrogen, C1-6alkyl and C6-14aryl; R9 and R10 are selected independently from the group consisting of hydrogen, C1-6alkyl, acyl and heterocyclecarbonyl (C(O)Het wherein Het is a heterocycle); R2 is selected from the group consisting of hydrogen, C1-6alkyl, C1-6alkenyl which may be substituted with one or more functional groups selected from the group consisting of hydroxyl, bromo, fluoro, chloro, iodo, mercapto or thio, cyano, C1-6alkylthio, heterocycle, C6-14aryl, heteroaryl, carboxyl, C1-6alkoxycarbonyl, C1-6alkyl, C1-6alkenyl, nitro, amino, C1-6alkoxyl, and amido; C6-14aryl, a heterocycle, aralkyl (RAr wherein R is C1-6alkyl which may be substituted and Ar is C6-14aryl, heteroaralkyl and trialkylsilyl (RR'R" Si wherein R, R' and R" are C1-6alkyl groups); or R2 is not present and the CO2 group to which it would be attached bears a negative charge; The ring A, B, D, and E is a carbon, nitrogen and sulphur containing heterocycle selected from the group consisting of thienyl, imidazolyl, thiazolyl thiadiazolyl and pyrazolyl.