FAB I INHIBITOR AND PROCESS FOR PREPARING SAME

摘要

A novel compound is provided to show broad anti-bacterial activity against Gram positive bacteria including methicillin resistant Staphylococcus Aureus (MRSA), thereby being useful for treating bacterial infections. A compound effective for inhibiting Fab I is represented by a formula(1) or (2). In the formulae, R1 is selected from the group consisting of: (a) H, (b) C1-8 alkyl, C1-8 alkenyl, C1-8 alkynyl, (c) aryl, C3-8 cycloalkyl, C3-8 cycloalkenyl, (d) an analog of a radical of group (c) containing at least one heteroatom selected from N, S and O, and (e) a substituted analog of a radical selected from the group consisting of groups (b), (c), and (d), the substituted analog containing at least one substituent selected from the group consisting of hydroxyl, halogen, C1-6 alkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, alkyloxy, amino, alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide, dioxoisoindole, trihaloalkyl, aryl, heteroaryl, substituted aryl, and substituted heteroaryl; A is CR2 or N; R2 is selected from the group consisting of H, C1-5 alkyl, benzyl, and substituted C1-5 alkyl; B is selected from the group consisting of carbonyl, CH2 and NH; R4 is selected from the group consisting of: (a) C1-8 alkyl, C1-8 alkenyl, C1-8 alkynyl, (b) aryl, C3-8 cycloalkyl, C3-8 cycloalkenyl, (c) an analog of a radical of group (b) containing at least one heteroatom selected from N, S and O, (d) a substituted analog of a radical selected from the group consisting of groups (a), (b), and (c), the substituted analog containing at least one substituent selected from the group consisting of hydroxyl, halogen, C1-6 alkyl, C3-8 cycloalkyl, C3-8 heterocycloalkyl, alkyloxy, amino, alkylamino, carboxyl, nitro, sulfonylamide, alkylsulfonyl, amide, dioxoisoindole, trihaloalkyl, aryl, heteroaryl, substituted aryl, and substituted heteroaryl; W is CR6 or N; Z is CR5 or N; each R5 and R5 is independently selected from the group consisting of H, halogen, C1-5 alkyl, and substituted C1-5 alkyl; and X is C, N, O or S. A method for preparing the compound of the formula(1) or (2) comprises the steps of: (a) forming a solution of a pyridone or pyridazine derivative comprising an alcohol or amine functionality and NaH or potassium t-butoxide in DMF; (b) combining the solution with a halide compound of the formula k-m-h(where h is chloride or bromide; m is benzyl, benzyloxy, or ylmethyl; and k is 2-chloro, 3-chloro, 4-chloro, 4-nitro, 2,5-dichloro, 2,4-dichloro, 4-menthoxy, 4-methyl, or 6-chloro-pyridin-3-, or 4-amino); and (c) stirring the combination for 30 minutes at room temperature to form a reaction product including at least one of the compounds of the formulae(1) and (2). An anti-bacterial composition comprises the compound of the formula(1) or (2) as an active ingredient. A kit for treating bacteria-related diseases comprises the anti-bacterial composition and a syringe.