Conformation-opioid activity relationships of bicyclic guanidines from 3D similarity analysis Article

Martínez-Mayorga, K, Medina-Franco, JL, Giulianotti, MA et al. (2008). Conformation-opioid activity relationships of bicyclic guanidines from 3D similarity analysis . BIOORGANIC & MEDICINAL CHEMISTRY, 16(11), 5932-5938. 10.1016/j.bmc.2008.04.061

cited authors

  • Martínez-Mayorga, K; Medina-Franco, JL; Giulianotti, MA; Pinilla, C; Dooley, CT; Appel, JR; Houghten, RA

authors

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. © 2008 Elsevier Ltd. All rights reserved.

publication date

  • June 1, 2008

published in

Digital Object Identifier (DOI)

start page

  • 5932

end page

  • 5938

volume

  • 16

issue

  • 11