Preparation of two Cyclobutadiene-steroid derivatives Theoretical Analysis of its Interaction with the μ, d, and k Opiod-receptors

Abstract

The objective of this investigation was to develop two cyclobutadiene-steroid derivatives (compounds 6 or 7) to evaluate its theoretical interaction on µ, d, and k opioid-receptors. The synthesis of 6 or 7 was carried out using a series of reactions which involves. 1) addition/cyclization: 2) imination, 3) etherification and 4) oxy-functionalization. Chemical structure of all compounds was confirmed using elemental analysis and NMR spectra. In addition, a theoretical analysis on the interaction of compounds 6 or 7 with µ, d, and k opioid-receptors was evaluated using a docking model. The results showed that 6 or 7 may interact with different type of amino acids residues on surface of the µ, d, and k opioid-receptors. Other data, indicated that inhibition constant (Ki) involved in the interaction of compounds 6 or 7 with k receptor was less compared with the Ki present in the interaction with µ, d, receptors. These data indicated that 1) compounds 6 or 7 show a high affinity by k-receptor; 2) the cyclobutadiene analogs are particularly interesting, because these drugs may constitute a novel therapy for pain.