Opioid selective ligands design

It is of particular interest that another 8 opioid selective nonpeptidic piperazine derivative agonist, SL-3111 (l-(4-/ert-butyl-3 -hydroxy)benzhydryl-4-benzylpiper-azine), was designed and synthesized based on the identification of the essential pharmacophores for peptide ligands to interact with 8 receptors, and on a model of the proposed bioactive conformation of the potent, conformationally constrained 8-opioid peptide ligand [(25,3/ )-TMT1]DPDPE [47]. This new series used the... 

Portoghese et al. (1987) have utilized a bivalent ligand approach in the design of selective ligands for opioid... 

Kazmierski, W. Hruby, V.J. (1988) A New Approach to Receptor Ligand Design -Synthesis and Conformation of a New Class of Potent and Highly Selective Mu-Opioid Antagonists Utilizing Tetrahydroisoquinoline Carboxylic-Acid Tetrahedron, Vol. 44, No. 3, pp. 697-710. 

NTI - starting point for the design of novel potent and selective 5 opioid ligands... 

A series of cyclic conformationally constrained peptides related to somatostatin were designed, synthesized and tested for opioid receptor interaction by Hruby and his collaborators. Compounds (17)-(22) were found to be pure opioid antagonists (GPI) with high affinity (IC50 = 1.2 to 4.3 nM) and exceptional selectivity for p over S opioid receptors (Table 3.1) and with minimal or no somatostatin-like activity (ligand binding assays)[63-65]. 

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