Interaction models of 3-methylfentanyl derivatives with mu opioid receptors
Abstract
AIM: To study the interaction model of 3-methylfentanyl derivatives with mu
opioid receptor.
METHODS: After a systematic conformational search, a three-dimensional
quantitative structure-activity relationship study was carried out with
comparative molecular field analysis (CoMFA).
RESULTS: 1) The 6 CoMFA models had good predictive values and each model
corresponded to the minimum-energy conformations of 13 compounds studied; 2) The
important geometric parameters of mu pharmacophore d1 (A), d2 (A), d3 (A), d4
(A), d5 (A), and d6 (A) were 5.2, 5.4, 4.9, 10.6, 10.2, and 5.8 in Model 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 Model 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 bioactive conformations of fentanyl analogs possibly
existed and did not need to be the absolute minimum-energy conformation, each of
which was involved in the interaction with mu opioid receptor.
Keywords:
opioid receptor.
METHODS: After a systematic conformational search, a three-dimensional
quantitative structure-activity relationship study was carried out with
comparative molecular field analysis (CoMFA).
RESULTS: 1) The 6 CoMFA models had good predictive values and each model
corresponded to the minimum-energy conformations of 13 compounds studied; 2) The
important geometric parameters of mu pharmacophore d1 (A), d2 (A), d3 (A), d4
(A), d5 (A), and d6 (A) were 5.2, 5.4, 4.9, 10.6, 10.2, and 5.8 in Model 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 Model 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 bioactive conformations of fentanyl analogs possibly
existed and did not need to be the absolute minimum-energy conformation, each of
which was involved in the interaction with mu opioid receptor.