NEW-TYPE OXAZOLIDINONE COMPOUNDS AND PREPARATION METHOD THEREFOR

Abstract

Oxazolidinones having structures represented by structural formula I, preparation methods therefor, and pharmaceutical uses thereof, in particular an application of said compounds and salts or compositions thereof in the treatment of a bacterial infection. In the formula: R.sup.1 is a methyl group, an ethyl group, a propyl group, a cyclopropyl group, or a vinyl group; R.sup.2 is F; and R.sup.3 is F, CH.sub.3, C.sub.2H.sub.5, CF.sub.3, CHF.sub.2, CH.sub.2F, or a cyclopropyl group.

Claims

1. An oxazolidinone compound of formula I and pharmaceutically acceptable salt thereof, ##STR00012## wherein R.sup.1 is methyl, ethyl, propyl or cyclopropyl, or vinyl; R.sup.2 is F; R.sup.3 is F, CH.sub.3, C.sub.2H.sub.5, CF.sub.3, CHF.sub.2, CH.sub.2F, or cyclopropyl.

2. The compound of claim 1, wherein the compound is selected from the group consisting of: (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxylmethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxylmethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoro-methyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-tri-fluoroethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoro-methyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroe-thyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoro-ethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoro-ethyl) oxazolidin-2-one phosphate (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclo-propylmethyl) oxazolidin-2-one phosphate.

3. A method for preparing the compound of formula I according to claim 1, comprising steps of reacting a compound having a structure of formula II with a halogenated phosphate ester, and reacting a resulting product with trimethylhalosilane ##STR00013## wherein R.sup.1 is methyl, ethyl, propyl, cyclopropyl, or vinyl; R.sup.2 is F; R.sup.3 is F, CH.sub.3, C.sub.2H.sub.5, CF.sub.3, CHF.sub.2, CH.sub.2F, or cyclopropyl.

4. A method for preparing the compound of formula I according to claim 1, comprising steps of reacting a compound having a structure of formula II with phosphorus oxychloride, and hydrolyzing a resulting product ##STR00014## wherein R.sup.1 is methyl, ethyl, propyl, cyclopropyl, or vinyl; R.sup.2 is F; R.sup.3 is F, CH.sub.3, C.sub.2H.sub.5, CF.sub.3, CHF.sub.2, CH.sub.2F, or cyclopropyl.

5. The method according to claim 3, wherein the halogenated phosphate ester is selected from the group consisting of dimethyl chlorophosphate, diethyl chlorophosphate, dibenzyl chlorophosphate, dimethyl bromophosphate, diethyl bromophosphate ester, and dibenzyl bromophosphate.

6. The method according to claim 3, wherein the trimethylhalosilane is selected from the group consisting of trimethylbromosilane and trimethylchlorosilane.

7. The method according to claim 3, wherein the compound having the structure of formula II is selected from the group consisting of the following compounds: (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxylmethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridine-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazole-5)-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxane oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxymethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl)) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl)) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl)) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl)) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-trifluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxyethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxypropyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(hydroxyfluoromethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (referred to as compound 51) (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-methyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-ethyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-propyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-cyclopropyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-difluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-2-fluoroethyl) oxazolidin-2-one (R)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one (S)-3-(3-fluoro-4-(6-(2-vinyl-2H-tetrazol-5-yl) pyridin-3-yl) phenyl)-5-(1-hydroxy-1-cyclopropylmethyl) oxazolidin-2-one.

8. A method for treating a bacterial infection disease, comprising a step of administering a compound of formula I according to claim 1 or formula II and salts thereof to a patient in need thereof ##STR00015##

9. (canceled)

Description

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0177] In order to better show the essence of the present disclosure and to implement the present disclosure, the following examples are provided. It should be appreciated by those skilled in the art that the embodiments are only for the purpose of exemplifying the process of the present disclosure, without affecting the scope of the present disclosure.

Example 1

[0178] Synthesis of Compound 1

[0179] One gram of 6-(2-ethyl-2H-tetrazol-5-yl)-3-bromopyridine was dissolved in 10 ml of toluene, then triphenylphosphine palladium chloride was added and the resulting mixture was stirred and warmed to a temperature of 40° C., and 1.2 g of (R)-3-(3-fluoro-4-bromophenyl)-5-(hydroxymethyl) oxazolidin-2-one was added dropwise to react. After completion of the addition, the reaction was held for 4 hours when the temperature was kept at 40-50° C. The reaction was terminated and the reaction mixture was filtered, the solvent was evaporated to dryness, and the residue was recrystallized from ethanol to afford 1.2 g of white solid. The purity detected by HPLC was 98.02%.

Example 2

[0180] Synthesis of Compound 2

[0181] 0.3 g of magnesium scraps was dissolved in 10 ml of anhydrous tetrahydrofuran, and 0.01 g of iodine was added. It could be observed that bubbles began to come out from the reaction solution. The reaction solution was stirred and a solution of 1 g of 6-(2-ethyl-2H-tetrazol-5-yl)-3-bromopyridine in 5 ml of anhydrous tetrahydrofuran was added dropwise. After addition, the resulting mixture was heated and refluxed for 2 hours. Then a solution of 1.2 g of (S)-3-(3-fluoro-4-bromophenyl)-5-(hydroxymethyl) oxazolidin-2-one in 5 ml of anhydrous tetrahydrofuran was added dropwise and the resulting mixture was refluxed for 4 hours. Work-up: 1 ml of water was added and stirred for 10 minutes, filtered, and the filtrate was evaporated to dryness, and the residue was recrystallized from ethanol to afford 1.1 g of white solid. The purity detected by HPLC was 98.11%.

Example 3

[0182] Compound 3 was synthesized using a method similar to that in Example 1.

Example 4

[0183] Synthesis of Compound 1:

[0184] In a 250 mL reaction flask were added DMSO (100 mL), (5R)-3-(4-bromo-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one (10.00 g, 34.5 mmol), pinacol diboronate (17.52 g, 69.0 mmol), [1,1′-bis (diphenylphosphino) ferrocene dichloropalladium-dichloromethane complex (1.39 g, 1.7 mmol) and potassium acetate (13.54 g, 138.0 mmol), and the resulting mixture was heated to 80° C. under nitrogen protection, and the reaction was carried out for 14 h. Heating was stopped, and the reaction system was cooled to room temperature. 500 mL of water was added, extracted with ethyl acetate (500 mL×3), the organic layers were combined, washed with saturated brine (400 mL×3), and dried over anhydrous sodium sulfate, the organic phase was filtered by suction filtration, concentrated and used directly for the next step of reaction.

[0185] The concentrated product from the previous step was added into a 250 mL reaction flask, then 1,4-dioxane (100 mL), 5-bromo-2-(2-methyl-2H tetrazol-5-yl)) pyridine (compound 3) (8.28 g, 34.5 mmol), [1,1′-bis (diphenyiphosphino) ferrocene]dichloropalladium-dichloromethane complex (0.57 g, 0.7 mmol) and cesium carbonate aqueous solution (50 mL, containing 33.72 g cesium carbonate, 103.5 mmol) were added, and the resulting mixture was heated to 70° C. under nitrogen protection. The reaction was performed for 3 hours and ended. Then dichloromethane (100 mL×3) was added for extraction. The separated organic phase was washed with saturated brine (100 mL), dehydrated with anhydrous sodium sulfate, filtered, concentrated in vacuo and purified by column chromatography to afford 10.60 g of compound 1 in a yield of 82.900 and a purity of 98.34% by HPLC.

[0186] A series of similar compounds were synthesized by methods similar to the methods described in Example 1, Example 2, and Example 4. The raw materials and products used are listed as follows.

TABLE-US-00001 Product No. [00008] [00009] 1 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = H 3 R.sup.1 = ethyl X = Cl, R.sup.2 = F, R.sup.3 = H 5 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = H 7 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = H 9 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = methyl 11 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 13 R.sup.1 = methyl X = I, R.sup.2 = F, R.sup.3 = F 15 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 17 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 19 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = methyl 21 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 23 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = F 25 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 27 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = methyl 29 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 31 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = F 33 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 35 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = methyl 37 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 39 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = F 41 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 43 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = methyl 45 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 47 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = F 49 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 51 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 53 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 55 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 57 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 59 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 61 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 63 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 65 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 67 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 69 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 71 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 73 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 75 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 77 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl

[0187] A series of similar compounds were synthesized by methods similar to the methods described in Example 1, Example 2, and Example 4. The raw materials and products used are listed as follows.

TABLE-US-00002 Product No. [00010] [00011] 2 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = H 4 R.sup.1 = ethyl X = I, R.sup.2 = F, R.sup.3 = H 6 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = H 8 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = H 10 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = methyl 12 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 14 R.sup.1 = methyl X = Cl, R.sup.2 = F, R.sup.3 = F 16 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 18 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 20 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = methyl 22 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 24 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = F 26 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 28 R.sup.1 = propyl X = I, R.sup.2 = F, R.sup.3 = methyl 30 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 32 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = F 34 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 36 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = methyl 38 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 40 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = F 42 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = trifluoromethyl 44 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = methyl 46 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = ethyl 48 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = F 50 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 52 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 54 R.sup.1 = methyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 56 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 58 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 60 R.sup.1 = ethyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 62 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 64 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 66 R.sup.1 = propyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 68 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 70 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 72 R.sup.1 = cyclopropyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl 74 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = difluoromethyl 76 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = fluoromethyl 78 R.sup.1 = vinyl X = Br, R.sup.2 = F, R.sup.3 = cyclopropyl

Example 5

[0188] Preparation of Compound 79:

[0189] 0.36 g of compound 1 was dissolved in 10 ml of acetonitrile, 0.30 g of phosphorus oxychloride was added, and the reaction mixture was heated under reflux for 20 hours. The reaction system was cooled to room temperature, and 1 g of water added and stirred for 1 hour. The solvent was removed under reduced pressure at 40° C. until the solvent was evaporated to dryness. The resulting residue was subjected to column chromatography and recrystallized from absolute ethanol to afford 0.28 g of white solid in a yield of 63% and a HPLC purity of 98.9%.

Example 6

[0190] Preparation of Compound 79:

[0191] 0.36 g of compound 1 was dissolved in 10 ml of acetonitrile, 0.28 g of dimethyl chlorophosphate was added, and the reaction mixture was heated under reflux for 20 hours. The reaction system was cooled to room temperature, 3 ml of methanol was added and stirred, and then 0.3 g of trimethylchlorosilane was added and stirred at room temperature for 3 hours. The solvent was evaporated to dryness, and the resulting residue was subjected to column chromatography and recrystallized from absolute ethanol to afford 0.33 g of white solid in a yield of 74% and a HPLC purity of 99.2%.

[0192] Compounds 80-156 were synthesized using a similar method to that in Example 5 and Example 6.

Example 7

[0193] In order to determine the antibacterial activity of these new oxazolidinone-based compounds, an agar dilution method was used to test the inhibitory effect on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). The bacteria inhibition effect was expressed as minimum inhibitory concentration (MIC50, μg/ml) The test results are shown in the following table.

TABLE-US-00003 Minimum inhibitory concentration (MIC50, μg/ml) compound MRSA VRE Tedizolid phosphate 2 2 79 1.8 1.5 80 1.9 1.9 81 1.2 1.2 82 1.2 1.2 83 0.8 0.7 84 0.4 0.4 85 0.2 0.2 86 0.3 0.3 87 0.3 0.3 88 0.5 0.5 89 0.4 0.4 90 2.0 2.0 91 1.3 1.3 92 0.9 0.9 93 0.7 0.7 94 1.5 1.5 95 0.3 0.3 96 0.8 0.8 97 1.1 1.1 98 1.6 1.5 99 0.2 0.2 100 0.2 0.3 101 0.4 0.4 102 0.2 0.2 103 0.7 0.7 104 0.5 0.5 105 1.4 1.3 106 1.0 1.2 107 0.8 0.8 108 0.5 0.4 109 0.2 0.2 110 0.2 0.2 111 0.3 0.3 112 0.9 0.9 113 0.2 0.2 114 0.3 0.3 115 0.5 0.5 116 0.2 0.3 117 0.4 0.4 118 0.6 0.6 119 0.7 0.7 120 0.2 0.2 121 1.1 1.1 122 1.0 0.9 123 0.3 0.3 124 0.2 0.2 125 0.3 0.3 126 0.7 0.7 127 0.6 0.7 128 0.5 0.5 129 0.5 0.3 130 0.2 0.2 131 0.2 0.1 132 0.3 0.3 133 0.3 0.2 134 0.5 0.5 135 0.4 0.3 136 0.4 0.2 137 1.5 1.1 138 1.0 1.0 139 0.8 0.9 140 0.4 0.4 141 0.3 0.2 142 0.2 0.2 143 0.3 0.2 144 0.4 0.4 145 0.6 0.5 150 0.2 0.2 151 0.8 0.6 152 0.3 0.2 153 0.2 0.1 154 0.4 0.3 155 0.9 0.5 156 0.4 0.4

[0194] As shown in the above table, when compared with tedizolid phosphate, the compounds of the present disclosure have stronger inhibitory effects on methicillin-resistant Staphylococcus aureus (referred to as MRSA) and vancomycin-resistant enterococcus (referred to as VRE). Therefore, the compounds of the present disclosure are very useful antibiotics.