Novel Meroterpenoids from Hypericum patulum : Highly Potent Late Na v 1.5 Sodium Current Inhibitors.

Hypulatones A and B (1 and 2), two racemic meroterpenoids possessing an unprecedented spiro[benzofuran-2,1'-cycloundecan]-4'-ene-4,6(5H)-dione core, were characterized from Hypericum patulum. Compound 2 was found to significantly inhibit the late current of Na(v)1.5 (late I-Na, IC50 = 0.2 mu M). Importantly, 2 exhibited remarkable separation (>100-fold) of late I-Na relative to peak I-Na and notable selectivity over Ca(v)3.1, K(v)1.5, and hERG. 1 showed comparable inhibition on late I-Na compared to that of 2 with poorer selectivity.