Synthesis and physiological effects of new 4-aminophenol derivatives as paracetamol analogues

Paracetamol has antipyretic and analgesic properties and it is widely used for fever and pain. However, paracetamol is partially metabolized to N-acetyl-p-benzoquinoneimine, which in overdose leads to liver necrosis, urging for safer paracetamol analogues. As the latter, new para-aminophenol derivatives containing fragments of acetic acid, saturated fatty acids and monoethanolamine were synthesized. The obtained compounds at equimolar doses of paracetamol (0.5 mmol/kg) have been shown to have modulating effect on thermoregulatory (in experimental fever) and nociceptive (in experimental arthritis) reactions. The studied derivatives in rats with LPS-induced fever leveled the first phase of the febrile response and reduced the increase in core body temperature in the second phase by three times. The synthesized compounds in rats with zymosan-induced arthritis suppressed the nociceptive response in Randall-Selitto test and Hot plate test by 21-48 % and 8-42 %, respectively.