Studying heterocycle synthesis using various methods including continuous flow chemistry and solid-phase synthesis, we are particularly interested in heterocyclic frameworks that serve as ligands for diverse receptors, so called “privileged structures”. Inspired by our recent crystallographic studies, we are studying diaze- and triazepinones as mimics of γ- and β-turn conformations. Employing these heterocycles in de novo designs to replicate the purported γ-turn conformer of the Trp-Lys-Tyr triad that is common to the two endogenous peptide ligands of the urotensin II receptor, we have conceived modulators that were shown in collaboration with Professor David Chatenet (Centre INRS) to differentiate receptor-mediated vasoconstriction offering unique utility to study selectively physiological regulation of various organ systems, particularly the cardiovascular system.
Figure 4. Benzotriazepinone and pyrrolodiazepinone Urotensin receptor modulators