title: Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands.
abstract: This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and Kiσ2 = 91.8 ± 8.1 nM).
authors.affiliation: Radioisotope Research Group, Nuclear Science Research School, NSTRI, Tehran, Iran. m.sadeghzadeh@ut.ac.ir
authors.forename: Masoud
authors.initials: M
authors.lastname: Sadeghzadeh
authors.forename: Shahab
authors.initials: S
authors.lastname: Sheibani
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghandi
authors.forename: Fariba Johari
authors.initials: FJ
authors.lastname: Daha
authors.forename: Massoud
authors.initials: M
authors.lastname: Amanlou
authors.forename: Mohammad
authors.initials: M
authors.lastname: Arjmand
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Hasani Bozcheloie
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008024:Ligands; D008297:Male; D008968:Molecular Conformation; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D008024:Ligands; D010879:Piperazines; D010880:Piperidines; D017447:Receptors, Dopamine D1; D000077489:Piperazine; C032727:piperidine