Synthesis and analgesic activity of new α-truxillic acid derivatives with monoterpenoid fragments

Abstract

Novel derivatives of α-truxillic acid with a camphor framework were synthesized and evaluated for their in vivo analgesic activity. α-Truxillic acid derivatives were prepared via solvent-free photocatalyzed [2+2] cyclodimerization of (E)-cinnamic acid. Target compounds were obtained through the substitution of –Cl or –OH groups in α-truxillic acid. The chemical structures of the synthesized compounds were elucidated by 1H, 13C-NMR, and mass spectrometry. Their analgesic activities were evaluated by the acetic acid-induced writhing test and the hot plate method. Compounds 7b and 7f containing the cyclobutane unit and natural fragments at 10 mg/kg exhibited analgesic activity in the acetic acid-induced writhing test, while α-truxillic acid (10 mg/kg, per os) did not show analgesic activity in the test. Intermediate 2 caused a decrease in the writhing with pain inhibition of 28 %. In the hot plate test, borneol showed high analgesic activity with pain inhibition of 60 %.