title: Design, synthesis, and preliminary pharmacological evaluation of 4-aminopiperidine derivatives as N-type calcium channel blockers active on pain and neuropathic pain.
abstract: Several compounds with a 4-aminopiperidine scaffold decorated on both nitrogen atoms by alkyl or acyl moieties containing the structural motifs of verapamil and of flunarizine, as well as those that are more frequent in known N-type calcium channel antagonists, have been synthesized. Antinociceptive activity on the mouse hot-plate test was used to select molecules to be submitted to further studies. Active compounds were tested in vitro on a PC12 rat pheochromocytoma clonal cell line, to evaluate their action on N-type calcium channels, and on a rat model of neuropathic pain. Two compounds that show N-type calcium channel antagonism and are endowed with potent action on pain and neuropathic pain (3 and 18) have been selected for further studies.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy. elisabetta.teodori@unifi.it
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Baldi
authors.forename: Silvia
authors.initials: S
authors.lastname: Dei
authors.forename: Fulvio
authors.initials: F
authors.lastname: Gualtieri
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Romanelli
authors.forename: Serena
authors.initials: S
authors.lastname: Scapecchi
authors.forename: Cristina
authors.initials: C
authors.lastname: Bellucci
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Matucci
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002074:Butanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects* / Q000378:metabolism; D002552:Cerebral Ventricles / Q000378:metabolism; D015195:Drug Design; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D016716:PC12 Cells; D010146:Pain / Q000188:drug therapy*; D010147:Pain Measurement; D017288:Pain Threshold; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
chemical_list: C494559:1-(4-aminopiperidin-1-yl)-4,4-bis(fluorophenyl)butan-1-one; D000700:Analgesics; D002074:Butanones; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D010880:Piperidines; D002118:Calcium