Synthesis and Preliminary in Vitro Investigation of Bivalent Ligands Containing Homo- and Heterodimeric Pharmacophores at Mu, Delta, and Kappa Opioid Receptors.
From: Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, Massachusetts 02478, USA.
Journal of medicinal chemistry
- Publish Date: Jan 2006
- ISSN: 0022-2623
- Volume: 49
- Issue: 1
- Pages: 256-62
- Medium: Print
- Language: English
- Citation (JAMA): Peng Xuemei, Knapp Brian I, Bidlack Jean M, et al. Synthesis and Preliminary in Vitro Investigation of Bivalent Ligands Containing Homo- and Heterodimeric Pharmacophores at Mu, Delta, and Kappa Opioid Receptors.. J. Med. Chem. Jan 2006;49:256-62
Abstract
A series of homo- and heterodimeric ligands containing kappa agonist and mu agonist/antagonist pharmacophores joined by a linker chain of varying lengths was synthesized and evaluated in vitro by their binding affinity at mu, delta, and kappa opioid receptors. The functional activities of these compounds were measured in the [(35)S]GTPgammaS binding assay. The data suggest that the stereochemistry of the pharmacophores, the N-substituents of the pharmacophore, ester linkages, and the spacer length were crucial factors for optimum interactions of such ligands at opioid receptor binding sites. These novel ligands as well as their pharmacological properties will serve as the basis for our continuing investigation of such bivalent ligands as probes of the opioid receptor oligomerization phenomena and for in vivo studies as analgesics.
Mesh Headings (Keywords): Animals, CHO Cells, Cricetinae, Drug Evaluation, Preclinical, Humans, Ligands, Molecular Conformation, Morphinans, Receptors, Opioid, delta, Receptors, Opioid, kappa, Receptors, Opioid, mu, Stereoisomerism, Structure-Activity Relationship
Check for Full Text / PubMed Unique Identifier (PMID): 16392810
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