Discovery of mu-opioid selective ligands derived from 1-aminotetralin scaffolds made via metal-catalyzed ring-opening reactions.

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Dockendorff C, Jin S, Olsen M, Lautens M, Coupal M, Hodzic L, Spear N, Payza K, Walpole C, Tomaszewski MJ

Discovery of mu-opioid selective ligands derived from 1-aminotetralin scaffolds made via metal-catalyzed ring-opening reactions.

Bioorg Med Chem Lett. 2009 Feb 15;19(4):1228-32. doi: 10.1016/j.bmcl.2008.12.095. Epub 2008 Dec 30.

PubMed ID

19168350 [ View in PubMed

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Abstract

A series of 1-aminotetralin scaffolds was synthesized via metal-catalyzed ring-opening reactions of heterobicyclic alkenes. Small libraries of amides and amines were made using the amino group of each scaffold as a handle. Screening of these libraries against human opioid receptors led to the identification of (S)-(S)-5.2a as a high-affinity selective mu ligand (IC(50)mu=5 nM, kappa=707 nM, delta=3,795 nM) displaying mu-agonist/antagonist properties due to its partial agonism (EC(50)=2.6 microM; E(max)=18%).

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Dezocine	Mu-type opioid receptor	EC 50 (nM)	38	N/A	N/A	Details
Meperidine	Mu-type opioid receptor	EC 50 (nM)	9400	N/A	N/A	Details