Preparation of a hexynloxy-diazecin-naphtho-oxadiazocine derivative. Theoretical analysis of its interaction with the µ, δ, and κ opioid-receptors

Some drugs have development with the purpose to evaluate its biological activity on opioid receptors; however, this phenomenon is not very clear, perhaps due to the established approach or to different types of chemical structures of each drug. The objective of this study was to synthesize a hexynloxy-diazecin-naphtho-oxadiazocine derivative (compound 6) to evaluate its theoretical interaction on µ,δ, and κ opioid-receptors. The preparation of 6 was carried out using a series of reactions which involves; 1) addition/cyclization; 2) imination and 3) etherification. Chemical structure of the compounds was confirmed using elemental analysis and NMR spectrum. The following stage involved the theoretical evaluation on the interaction of compound 6 with the µ,δ,κ-opioid receptors surface using a docking model. The results showed that compound 6 can interact with different type of aminoacid residues of µ-opioid receptor (Thr₁₁₁, Phe₁₁₄, Val₁₁₈, Lys₂₂₇, Glu₂₉₇, Tyr₃₁₂) compared with the interaction with the δ and κ-opioid receptors. In conclusion all these data suggest that hexynloxy-diazecin-naphtho-oxadiazocine derivative is a particularly interesting, because involves higher interaction with µ-opioid receptor; these data indicate that compound 6 could be an alternative for the treatment of pain.