{"doi":"10.1016/j.bmc.2006.01.061","title":"Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain","abstract":null,"journal":"Bioorganic & Medicinal Chemistry","year":2006,"id":673184,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":369188,"name":"Yukiko Miyamoto","orcid":"0000-0001-5650-699X","position":1,"is_corresponding":false},{"id":1758850,"name":"Emi Kobayashi","orcid":null,"position":2,"is_corresponding":false},{"id":1758851,"name":"Mika Shimazaki","orcid":null,"position":3,"is_corresponding":false},{"id":1185025,"name":"Keiko Yamamoto","orcid":null,"position":4,"is_corresponding":false},{"id":1758853,"name":"Wolfgang Reischl","orcid":null,"position":5,"is_corresponding":false},{"id":1758854,"name":"Sachiko Yamada","orcid":null,"position":6,"is_corresponding":false},{"id":250971,"name":"Masato Shimizu","orcid":"0000-0003-1237-7633","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Synthesis and biological activities of new 1α,25-dihydroxy-19-norvitamin D3 analogs with modifications in both the A-ring and the side chain","abstract":"In a series of studies on structure-activity relationships of 2-substituted 19-norvitamin D analogs, we found that 1alpha,25-dihydroxy-19-norvitamin D3 analogs with 2beta-hydroxyethoxy or 2E-hydroxyethylidene moieties show strong binding affinity for the vitamin D receptor (VDR) as well as marked transcriptional activity. To further examine the effects of side chain structure on the activity of 2-substituted 19-norvitamin D analogs, we have synthesized new 19-norvitamin D3 analogs with modifications in both the A-ring at the C(2) position and the side chain. The side chains of these analogs contained a double bond between C(22) and C(23) or an oxygen atom at C(22). The biological activity of the analogs was evaluated in vitro. All the side chain-modified analogs were less active than 1alpha,25-dihydroxyvitamin D31e and the parent compounds 3-6e possessing a natural 20R-configuration in binding to the VDR, but, except for the (20R)-22-oxa analogs 3-6d, were significantly more potent in transcriptional activity. Of the side-chain-modified analogs 4 and 5, the 2beta-hydroxyethoxy- and 2E-hydroxyethylidene-22,24-diene-24a,26a,27a-trihomo analogs showed markedly higher transcriptional activity (25- and 17.5-fold, respectively) compared with 1e. Elongation of the side chain at the C-24, C-26, and C-27 positions and introduction of a 22,24-diene moiety strongly increased transcriptional activity, as seen in the 20-epi analogs 3-6f.","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"16503143","pmcid":null,"openalex_id":"https://openalex.org/W2017201663","authors":[],"funders":[],"total_grants":0,"fwci":0.7709,"citation_percentile":0.72908298,"influential_citations":0,"citation_trend":[{"year":2014,"count":1},{"year":2016,"count":1},{"year":2019,"count":1},{"year":2020,"count":1},{"year":2022,"count":2}],"oa_status":"closed","license":"https://www.elsevier.com/legal/tdmrep-license","oa_locations":[{"url":"https://api.elsevier.com/content/article/PII:S0968089606001350?httpAccept=text/xml","host_type":"publisher"},{"url":"https://api.elsevier.com/content/article/PII:S0968089606001350?httpAccept=text/plain","host_type":"publisher"},{"url":"https://doi.org/10.1016/j.bmc.2006.01.061","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/16503143","host_type":"repository"}],"fields_of_study":["Vitamin D Research Studies","Biotin and Related Studies","Estrogen and related hormone effects","Medicine","Chemistry"],"mesh_terms":["Animals","Binding Sites","Calcitriol","Chlorocebus aethiops","Drug Evaluation, Preclinical","Ligands","Molecular Conformation","Stereoisomerism","Structure-Activity Relationship","Transcription, Genetic","Receptors, Calcitriol","COS Cells","Rats","In Vitro Techniques"],"keywords":["Chemistry","Side chain","Calcitriol receptor","Stereochemistry","Biological activity","Moiety","Ring (chemistry)","Double bond","Molecular model","Chemical synthesis","In vitro","Receptor","Biochemistry","Organic chemistry"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Clean water and sanitation"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-16T12:38:47.685160Z","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":[]}