title: Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.
abstract: New I(f) blockers have been designed and tested on HEK293 cells stably expressing the HCN1, HCN2, and HCN4 channels to find compounds able to discriminate among the channel isoforms. Among the synthesized compounds, the cis-butene derivative (R)-5 shows some preference for HCN2 while the pseudodimeric product (R)-6 shows selectivity for HCN1. These compounds can be important pharmacological tools to study the channels in native tissues and may be useful to design safe drugs.
authors.affiliation: Laboratory of Design, Synthesis, and Study of Biologically Active Heterocycles (HeteroBioLab), Department of Pharmaceutical Sciences, Via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Melchiorre
authors.forename: Martina
authors.initials: M
authors.lastname: Del Lungo
authors.forename: Luca
authors.initials: L
authors.lastname: Guandalini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Martini
authors.forename: Silvia
authors.initials: S
authors.lastname: Dei
authors.forename: Dina
authors.initials: D
authors.lastname: Manetti
authors.forename: Serena
authors.initials: S
authors.lastname: Scapecchi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
authors.forename: Laura
authors.initials: L
authors.lastname: Sartiani
authors.forename: Alessandro
authors.initials: A
authors.lastname: Mugelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cerbai
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Romanelli
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D051379:Mice; D009124:Muscle Proteins / Q000037:antagonists & inhibitors*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels; D011437:Propylamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors; D013237:Stereoisomerism; D013268:Stimulation, Chemical
chemical_list: D001552:Benzazepines; D054815:Cyclic Nucleotide-Gated Cation Channels; C578665:HCN1 protein, human; C578710:HCN2 protein, human; C119587:HCN4 protein, human; C578666:Hcn1 protein, mouse; C578711:Hcn2 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009124:Muscle Proteins; C552713:N,N-bis(4-(7,8-dimethoxy-2-oxo-1,3-dihydrobenzo(d)azepin-3-yl)but-2-enyl)-2-(3,4-dimethoxyphenyl)propanamine; D015221:Potassium Channels; D011437:Propylamines; D020033:Protein Isoforms