Influence of ethylene-Oxy spacer group on the activity of linezolid: Synthesis of potent antibacterials possessing a thiocarbonyl group

The influence of an ethylene-oxy spacer element between the heterocycle and the aromatic ring in linezolid is reported. The introduction of such spacer group generated compounds with inferior antibacterial activity. However, the conversion of the acetamide group present in the linezolid analogues to either thiocarbamate or thioacetamide functionality restored the activity. The synthesis of linezolid analogues possessing the ethylene-oxy spacer group along with SAR studies with different heterocycles and preparation of some thiocarbonyl compounds possessing potent antibacterial property are presented. The introduction of ethylene-oxy spacer group in linezolid, subsequent SAR studies with different heterocycles and conversion of some of the compounds to their thiocarbonyl counterparts resulted in certain interesting antibacterial compounds.