3,5-disubstitution of the benzyl ring in the ether series gave greater potency than the 2-methoxy substitution in earlier benzylamine structures. it also was revealed that the tfmp group appeared to be especially important, and it is believed that it enhances activity in vivo and improves metabolism. other groups, like the ortho-methoxyphenyl group, can be important in specific cases, but are thought to play a greater role in ligand preorganization through intramolecular hydrogen bonding, rather than through direct interaction with binding site residue. the presence of an intramolecular face-to-face π–π interaction between two aromatic rings is a common feature of high affinity nk1 receptor antagonists. this feature is thought to be important in stabilizing the bioactive conformation. this interaction can be increased with a conformationally-restricted system, such as an eight-membered ring introduced into the naphthyridine ring. future development fig 7. t-2328 chemotherapy-induced emesis is a major problem in cancer treatment. a new compound, t-2328 (figure 7), a non-peptide antagonist of the tachykinin nk1 family, is studied for that purpose. t-2328 is administered intravenously, and treats both acute and delayed emesis. it is proposed to exert its anti-emetic effect through acting on brain nk1 receptors. t-2328 is very potent; the inhibition constant is of subnanomolar range and is 16 times lower than that of aprepitant. the inhibition is highly selective for nk1 receptors. the nk2 and nk3 receptors are also targets for novel classes of medications, and also show prominent antidepressive and anxiolytic effects. studies showed that the inhibition constant (ki) for nk2 receptors was >10000-fold higher and for nk3 receptors >1000-fold higher than that for nk1 receptors. the affinity was also much lower for nk2 and nk3 receptors. since tachykinins were discovered, they have been shown to possess biological activity in number of pathological and physiological systems. nevertheless, the therapeutic potential of the tachykinin antagonists has not been fully understood.