AT-076

AT-076

Systematic (IUPAC) name
(3R)-7-hydroxy-N-[(2S)-1-[4-(3-hydroxyphenyl)piperidin-1-yl]-3-methylbutan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
Chemical data
Formula	C26H35N3O3
Molar mass	437.573
SMILES C4c1ccc(O)cc1CNC4C(=O)NC(C(C)C)CN(CC3)CCC3c(ccc2)cc2O

AT-076 is a so-called opioid "pan" antagonist and is the first reasonably balanced antagonist known of all four opioid receptor types.^[1] It acts as a silent antagonist of all four of the opioid receptors, behaving as a competitive antagonist of the μ-opioid receptor (K_i = 1.67 nM) and δ-opioid receptor (K_i = 19.6 nM) and as a noncompetitive antagonist of the κ-opioid receptor (K_i = 1.14 nM) and nociceptin receptor (K_i = 1.75 nM).^[1] AT-076 was derived from the selective κ-opioid receptor antagonist JDTic via removal of the 3,4-dimethyl group of the trans-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine antagonist scaffold, which increased affinity for the nociceptin receptor by 10-fold and for the μ- and δ-opioid receptors by 3-6-fold.^[1]

See also

• Cebranopadol
• Buprenorphine
• BU09059

References

1. Zaveri NT, Journigan VB, Polgar WE (2015). "Discovery of the First Small-Molecule Opioid Pan Antagonist with Nanomolar Affinity at Mu, Delta, Kappa, and Nociceptin Opioid Receptors". ACS Chem Neurosci 6: 646–57. doi:10.1021/cn500367b. PMID 25635572.