Compounds 1c and 1f, together with 1b and 1d, were studied in basolateral-to-apical transport experiments applying the Caco-2 cell monolayer model, to determine potential P-gp-mediated cellular efflux by semi-quantitative LC/MS analysis. As expected, basolateral-to-apical transport of the P-gp substrate digoxin was significantly inhibited in the presence of the P-gp inhibitor zosuquidar (ZSQ, LY335979 (32); Figure ). Interestingly, compounds 1b, 1c and 1d showed relatively high passive permeability that was even greater than that of digoxin, whereas the transcellular passive diffusion of 1f was similarly high as with digoxin (Figure ). Inhibition of Pgp by ZSQ did not significantly reduce the apical concentration of 1b, 1d and 1f (Figure ) and had only a very modest, yet significant, effect on 1c compared to the highly