Discovery of novel triazole-based opioid receptor antagonists.
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).
Zhang
Qiang
Q
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.
Keenan
Susan M
SM
Peng
Youyi
Y
Nair
Anil C
AC
Yu
Seong Jae
SJ
Howells
Richard D
RD
Welsh
William J
WJ
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
D008024:Ligands; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D014230:Triazoles