title: Discovery of novel triazole-based opioid receptor antagonists.
abstract: We report the computer-aided design, chemical synthesis, and biological evaluation of a novel family of delta opioid receptor (DOR) antagonists containing a 1,2,4-triazole core structure that are structurally distinct from other known opioid receptor active ligands. Among those delta antagonists sharing this core structure, 8 exhibited strong binding affinity (K(i) = 50 nM) for the DOR and appreciable selectivity for delta over mu and kappa opioid receptors (delta/mu = 80; delta/kappa > 200).
authors.affiliation: Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey and UMDNJ Informatics Institute, Piscataway, New Jersey 08854, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Susan M
authors.initials: SM
authors.lastname: Keenan
authors.forename: Youyi
authors.initials: Y
authors.lastname: Peng
authors.forename: Anil C
authors.initials: AC
authors.lastname: Nair
authors.forename: Seong Jae
authors.initials: SJ
authors.lastname: Yu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Howells
authors.forename: William J
authors.initials: WJ
authors.lastname: Welsh
mesh_terms: D002460:Cell Line; D006801:Humans; D008024:Ligands; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D008024:Ligands; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014230:Triazoles