title: Gaining in pan-affinity towards sigma 1 and sigma 2 receptors. SAR studies on arylalkylamines.
abstract: Sigma Receptor (SR) modulators are involved in different signal transduction pathways, representing important pharmacological/therapeutic tools in several pathological conditions, such as neurodegenerative diseases and cancers. To this purpose, numerous compounds have been developed in order to target selectively one of the two subtypes (S1R and S2R) as chemotherapeutic agent. However, experiments have also shown that ligands which are able to bind both SR subtypes can be useful for the diagnosis and/or the treatment of cancers. Therefore, the discovery of compounds with good affinity towards both S1R and S2R ('pan-modulators') is also of great interest and still represents a challenge up to now. For this reason, we synthesized novel arylalkylamines with the aim to obtain compounds with S1R and S2R affinity in the nM range and, by modeling quantitative structure-activity relationships (QSARs), we identified the essential structural features to obtain promising pan-compounds.
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rossi
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Marta
authors.initials: M
authors.lastname: Rui
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Di Giacomo
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, University of Muenster, Correnstrasse 48, 48149 Muenster, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schepmann
authors.affiliation: Institute of Pharmaceutical and Medicinal Chemistry, University of Muenster, Correnstrasse 48, 48149 Muenster, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wünsch
authors.affiliation: Institute of General, Inorganic and Theoretical Chemistry, Center of Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Stefania
authors.initials: S
authors.lastname: Monteleone
authors.affiliation: Institute of General, Inorganic and Theoretical Chemistry, Center of Molecular Biosciences, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Liedl
authors.affiliation: Department of Drug Sciences, Medicinal Chemistry and Pharmaceutical Technology Section, University of Pavia, Viale Taramelli 12, 27100 Pavia, Italy. Electronic address: simona.collina@unipv.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Collina
mesh_terms: D000478:Alkylation; D000586:Amination; D000588:Amines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D055808:Drug Discovery; D006168:Guinea Pigs; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000097605:Sigma-1 Receptor
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor
keywords: Arylalkylamine; Pan-affinity; QSAR; Sigma receptors