INTERACTION MODELS OF 3-METHYLFENTANYL DERIVATIVES WITH MU-OPIOID RECEPTORS

AIM: To study the interaction model of 3-methylfentanyl derivatives wi th mu opioid receptor. METHODS: After a systematic conformational sear ch, a three-dimensional quantitative structure-activity relationship s tudy was carried,out with comparative molecular field analysis (CoMFA) . RESULTS: 1) The 6 CoMFA models had good predictive values and each m odel corresponded to the minimum-energy conformations of 13 compounds studied; 2) The important geometric parameters of mu pharmacophore d(1 )(Angstrom), d(2)(Angstrom), d(3)(Angstrom), d(4)(Angstrom), d(5)(Angs trom), and d(6)(Angstrom) were 5.2, 5.4, 4.9, 10.6, 10.2, and 5,8 in M odel A; 5.2, 6.5, 3.6, 10.6, 11.6, and 5.8 in Model B; 5.2, 4.6, 4.9, 11.6, 9.2, and 6.5 in Model C; 5.2, 5.4, 4.9, 10.5, 10.3, and 5.8 in M odel D; 3.6, 5.4, 4.9, 5.7, 7.5, and 5.7 in Model E; 5.2, 4.7, 4.9, 11 .2, 9.5, and 6.4 in Model F, respectively. CONCLUSIONS: The several bi oactive conformations of fentanyl analogs possibly existed and did not need to be the absolute minimum-energy conformation, each of which wa s involved in the interaction with mu opioid receptor.