Title of article
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 Original Research Article
Author/Authors
Claudio Trapella، نويسنده , , Carmela Fischetti، نويسنده , , Michela Pela، نويسنده , , Ilaria Lazzari، نويسنده , , Remo Guerrini، نويسنده , , Girolamo Caloʹ، نويسنده , , Anna Rizzi، نويسنده , , Valeria Camarda، نويسنده , , David G. Lambert، نويسنده , , John McDonald، نويسنده , , Domenico Regoli، نويسنده , , Severo Salvadori، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2009
Pages
16
From page
5080
To page
5095
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 CHOhNOP 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 (pA2 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.
Keywords
UDP , UMP analogs , Acyclic ribose modification , Nucleotide analogs , Phosphonates , P2Y2 receptors , UTP
Journal title
Bioorganic and Medicinal Chemistry
Serial Year
2009
Journal title
Bioorganic and Medicinal Chemistry
Record number
1306168
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