title: Decahydrobenzoquinolin-5-one sigma receptor ligands: Divergent development of both sigma 1 and sigma 2 receptor selective examples.
abstract: Analogues of the decahydrobenzoquinolin-5-one class of sigma (σ) receptor ligands were used to probe the structure-activity relationship trends for this recently discovered series of σ ligands. In all, 29 representatives were tested for σ and opioid receptor affinity, leading to the identification of compounds possessing improved σ1selectivity and, for the first time in this series, examples possessing preferential σ2affinity. Several structural features associated with these selectivity trends have been identified. Two analogues of improved selectivity were evaluated in a binding panel of 43 CNS-relevant targets to confirm their sigma receptor preference.
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Delbert M. Shankel Structural Biology Center, 2121 Simons Drive, Lawrence, KS 66047, United States.
authors.forename: Michael C
authors.initials: MC
authors.lastname: McLeod
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Delbert M. Shankel Structural Biology Center, 2121 Simons Drive, Lawrence, KS 66047, United States.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Aubé
authors.affiliation: Department of Medicinal Chemistry, University of Kansas, Delbert M. Shankel Structural Biology Center, 2121 Simons Drive, Lawrence, KS 66047, United States. Electronic address: kevinf@unc.edu.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Frankowski
mesh_terms: D055808:Drug Discovery; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry* / Q000494:pharmacology*; D011869:Radioligand Assay; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship; D000097605:Sigma-1 Receptor
chemical_list: D008024:Ligands; D011804:Quinolines; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor; C037920:decahydroquinoline-5-carboxylic acid
keywords: Biology-oriented synthesis; CNS; Decahydroquinoline; Radioligand binding; Sigma receptor; Structure-affinity relationship