Synthesis, spectroscopic, and X-ray structural characterization of pharmacologically active substituted pyrazolyl-acetanilides

Five new pyrazole acetanilides were synthesized by N-alkylation of pyrazole and its derivatives with 4'-propionyl-2-iodoacetanilide. Compounds 1-5 were characterized by H-1 NMR, C-13 NMR, IR, UV-Vis, MS, and elemental analysis. X-ray structures of representative compounds 1, 3, and 5 established their conformations and solid-state hydrogen bonding preferences. Acute toxicity, local anesthetic, and antiarrhythmic activities were assessed for compounds 1-5 using established protocols. Lower potencies and lower acute toxicities were recorded relative to lidocaine. Enhanced anesthetic activity of compound 3 was attributed to the presence of the propionyl group in the molecule.