Syhthetic Models Related to Furanocoumarin--CYP3A4 Interactions. Synthesis of Furanocoumarin Dimers that Have Inhibitory Effects on Activity of Human CYP3A4

Synthesis of a series of furanocoumarin dimers that have inhibitory effects on the activity of human cytochrome P450 (CYP) 3A4 is described. The reported furanocoumarin dimers paradisins A and B from grapefruit juice showed potent CYP3A4 inhibition with an IC 5 0 value of 0.07 μM. Synthetic furanocoumarin dimer (10), which is more stable and accessible than paradisins, exhibited comparable activity against CYP 3A4 (IC 5 0 = 0.02 μM).