Structure-activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide.

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Trapella C, Fischetti C, Pela' M, Lazzari I, Guerrini R, Calo' G, Rizzi A, Camarda V, Lambert DG, McDonald J, Regoli D, Salvadori S

Structure-activity studies on the nociceptin/orphanin FQ receptor antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide.

Bioorg Med Chem. 2009 Jul 15;17(14):5080-95. doi: 10.1016/j.bmc.2009.05.068. Epub 2009 Jun 2.

PubMed ID

19527931 [ View in PubMed

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Abstract

Twelve derivatives of the nociceptin/orphanin FQ (N/OFQ) receptor (NOP) antagonist 1-benzyl-N-{3-[spiroisobenzofuran-1(3H),4'-piperidin-1-yl]propyl} pyrrolidine-2-carboxamide (Comp 24) were synthesized and tested in binding experiments performed on CHO(hNOP) cell membranes. Among them, a novel interesting NOP receptor antagonist (compound 35) was identified by blending chemical moieties taken from different NOP receptor ligands. In vitro in various assays, Compound 35 consistently behaved as a pure, highly potent (pA(2) in the range 8.0-9.9), competitive and NOP selective antagonist. However compound 35 was found inactive when challenged against N/OFQ in vivo in the mouse tail withdrawal assay. Thus, the usefulness of the novel NOP ligand compound 35 is limited to in vitro investigations.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Naloxone	Kappa-type opioid receptor	Ki (nM)	4.47	N/A	N/A	Details
Naloxone	Mu-type opioid receptor	Ki (nM)	0.562	N/A	N/A	Details