{"doi":"10.17615/kv64-d967","title":"Identification of the Benzyloxyphenyl Pharmacophore: A Structural Unit That Promotes Sodium Channel Slow Inactivation","abstract":"Four compounds that contained the N-benzyl 2-amino-3-methoxypropionamide unit were evaluated for their ability to modulate Na+ currents in catecholamine A differentiated CAD neuronal cells. The compounds differed by the absence or presence of either a terminal N-acetyl group or a (3-fluoro)benzyloxy moiety positioned at the 4′-benzylamide site. Analysis of whole-cell patch-clamp electrophysiology data showed that the incorporation of the (3-fluoro)benzyloxy unit, to give the (3-fluoro)benzyloxyphenyl pharmacophore, dramatically enhanced the magnitude of Na+ channel slow inactivation. In addition, N-acetylation markedly increased the stereoselectivity for Na+ channel slow inactivation. Furthermore, we observed that Na+ channel frequency (use)-dependent block was maintained upon inclusion of this pharmacophore. Confirmation of the importance of the (3-fluoro)benzyloxyphenyl pharmacophore was shown by examining compounds where the N-benzyl 2-amino-3-methoxypropionamide unit was replaced by a N-benzyl 2-amino-3-methylpropionamide moiety, as well as examining a series of compounds that did not contain an amino acid group but retained the pharmacophore unit. Collectively, the data indicated that the (3-fluoro)benzyloxyphenyl unit is a novel pharmacophore for the modulation of Na+ currents.","journal":"UNC Libraries","year":2020,"id":135470,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.95,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":317835,"name":"Yuying Wang","orcid":"0009-0000-3482-4110","position":1,"is_corresponding":false},{"id":548664,"name":"Sarah M. Wilson","orcid":"0000-0002-1536-972X","position":2,"is_corresponding":false},{"id":592959,"name":"Andrew D. Piekarz","orcid":null,"position":3,"is_corresponding":false},{"id":548996,"name":"Amber M. King","orcid":null,"position":4,"is_corresponding":false},{"id":152546,"name":"Fletcher A. White","orcid":"0000-0002-8408-9262","position":5,"is_corresponding":false},{"id":592217,"name":"Michael R. Due","orcid":"0000-0001-6771-7100","position":6,"is_corresponding":false},{"id":547012,"name":"Christophe Salomé","orcid":"0000-0001-9668-8134","position":7,"is_corresponding":false},{"id":427082,"name":"Harold Kohn","orcid":null,"position":8,"is_corresponding":false},{"id":548666,"name":"Rajesh Khanna","orcid":"0000-0002-2331-1667","position":9,"is_corresponding":false},{"id":592218,"name":"Cindy Barbosa","orcid":"0000-0002-0938-3883","position":10,"is_corresponding":false},{"id":592219,"name":"Erik T. Dustrude","orcid":"0000-0002-1753-8603","position":11,"is_corresponding":false},{"id":592220,"name":"Yang Xiao","orcid":"0000-0002-7739-4146","position":12,"is_corresponding":false},{"id":276991,"name":"Theodore Cummins","orcid":"0000-0001-9509-6380","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:31.787520Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}