SYNTHESIS OF SOME NEW PYRAZOLE DERIVATIVES AS ANTIBACTERIAL AGENTS

Small organic phenylpyrazole scaffolds with high lipophilic properties are often associated with poor physicochemical properties, leading to more off-target actions and lower chances of full clinical trials. Therefore, we targeted the lipophilic tail of metabolically stable alkynylphenylpyrazole derivatives that exhibit remarkably high lipophilic properties and introduced a cyclic amine to improve their physicochemical characteristics. Alkynyl derivatives with 4-membered rings were the only ones that exhibited significant antibacterial activity. The azetidine moiety-containing compound 8 showed moderate antibacterial activity against MRSA. It significantly enhanced the water solubility and pharmacokinetic profile with an increase in the half-life and the time during which its plasma concentration was above its minimum inhibitory concentration against MRSA. The pharmacokinetic properties of the new series were successfully improved while the biological activity of the compounds against MRSA was maintained by the modifications of the alkynylphenylpyrazoles described here.