0000000000594044
AUTHOR
Carmen Almansa
showing 2 related works from this author
Pharmacological characterization of high-affinity σ1 receptor ligands with spirocyclic thienopyran and thienofuran scaffold
2019
Abstract Objectives In this study, the pharmacological properties of six spirocyclic piperidines 1–6 showing very high σ1 receptor affinity (Ki = 0.2–16 nm) were investigated. Methods In vitro receptor binding studies, retinal ganglion assay and in vivo capsaicin assay were used to determine the affinity, selectivity and activity. Influence on human tumour cell growth (cell lines A427, LCLC-103H, 5637 and DAN-G) was determined in different assays. The effect on the ergosterol and cholesterol biosynthesis was determined by GLC/MS analysis. Key findings Receptor binding studies demonstrated high selectivity for the σ1 receptor. The increased Ca2+ influx mediated by 2 and the analgesic activit…
Synthesis and Structure-Affinity Relationships of Spirocyclic Benzopyrans with Exocyclic Amino Moiety
2019
σ1 and/or σ2 receptors play a crucial role in pathological conditions such as pain, neurodegenerative disorders, and cancer. A set of spirocyclic cyclohexanes with diverse O-heterocycles and amino moieties (general structure III) was prepared and pharmacologically evaluated. In structure-activity relationships studies, the σ1 receptor affinity and σ1:σ2 selectivity were correlated with the stereochemistry, the kind and substitution pattern of the O-heterocycle, and the substituents at the exocyclic amino moiety. cis-configured 2-benzopyran cis-11b bearing a methoxy group and a tertiary cyclohexylmethylamino moiety showed the highest σ1 affinity ( Ki = 1.9 nM) of this series of compounds. In…