Synthesis and vasorelaxation evaluation of novel biphenyl–furocoumarin derivatives

Abstract

A series of novel biphenyl–furocoumarin derivatives were synthesized and evaluated for their vasorelaxant activities in vitro against rat mesenteric artery, basilar artery, and renal artery ring models pre-contracted by high KCl. The results showed that compounds 12b, 13b, 13d, 14b, and 14d exhibited good broad spectrum vasorelaxant activities on three kinds of rat artery ring models compared to imperatorin. Noteworthy, most of the compounds had potent good selectivity against mesenteric artery in which compound 14c exhibited highest vasodilation activity (pEC50 = 6.44, Emax = 105.8 %). These were suggested that the introduction of biphenyl in imperatorin was useful to improve vasodilation activities. The preliminary structure–activity relationships studies revealed that larger halogen substituent R1 on phenyl ring and smaller nitrogenous base R2 were favorable for vasorelaxant activities. In addition, the CoMFA model showed acceptable correlative and predictive abilities (r2 = 0.875, q2 = 0.502).