5-Nitrofuran-Tagged Oxazolyl Pyrazolopiperidines: Synthesis and Activity against ESKAPE Pathogens.

Elizaveta RogachevaLiudmila A Kraeva Alexey LukinLyubov VinogradovaKristina KomarovaMikhail V Chudinov Maxim A Gureev Evgeny Chupakhin

Published in: Molecules (Basel, Switzerland) (2023)

A series of eight 5-nitrofuran-tagged oxazolyl tetrahydropyrazolopyridines (THPPs) has been prepared in six stages with excellent regioselectivity. The testing of these compounds against pathogens of the ESKAPE panel showed a good activity of lead compound 1-(2-methoxyethyl)-5-(5-nitro-2-furoyl)-3-(1,3-oxazol-5-yl)-4,5,6,7-tetrahydro-1 H -pyrazolo[4,3-c] pyridine ( 13g ), which is superior to nitrofurantoin. These results confirmed the benefit of combining a THPP scaffold with a nitrofuran warhead. Certain structure-activity relationships were established in the course of this study which were rationalized by the induced-fit docking experiments in silico.

Keyphrases

gram negative
antimicrobial resistance
molecular dynamics
high glucose
diabetic rats
molecular dynamics simulations
multidrug resistant
drug induced
oxidative stress
small molecule