Conformation-opioid activity relationships of bicyclic guanidines from 3D similarity analysis |
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Authors: | Martínez-Mayorga Karina Medina-Franco Jose L Giulianotti Marc A Pinilla Clemencia Dooley Colette T Appel Jon R Houghten Richard A |
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Institution: | Torrey Pines Institute for Molecular Studies, 5775 Old Dixie Highway, Fort Pierce, FL 34946, USA. kmartinez@tpims.org |
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Abstract: | Conformation of bicyclic guanidines with kappa-opioid receptor activity derived in our laboratory from a positional scanning synthetic combinatorial library is presented in this work. We propose a common bioactive conformation and putative pharmacophoric features by means of 3D similarity methods. Our 'Y' shape molecular binding model explains structure-activity relationships and suggests that the guanidine functionality and a 4-methoxybenzyl group may be involved in key interactions with the receptor. Comparison of our model with known opiates suggest a similar binding mode showing that the bicyclic guanidines presented in this work are suitable scaffolds for further development of new opioid receptors ligands. |
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