Active conformations of neotame and other high-potency sweeteners

We carried out extensive conformational analysis of three high-potency swee teners: neotame, superaspartame, and SC-45647. me then identified six possi ble pharmacophore features (carboxylate, two hydrophobic groups, and three NH groups) and wrote a computer program to exhaustively compare intramolecu lar distances among all possible sets of five-point pharmacophores (carboxy late + two hydrophobic groups + two NH groups) for the three compounds. The best pharmacophore model superimposes low-energy conformers of the three c ompounds in such a way that the five pharmacophore points match well both s terically and with respect to orientation of hydrogen bond donors and accep tors.