{"doi":"10.1016/j.bmcl.2024.130003","title":"Synthesis and biological evaluation of 4,7,9-trisubstituted benzoxazepines as antileishmanial agents","abstract":"Herein we report a series of antileishmanial analogues derived from 4-[(3,5-dimethyl-4-isoxazolyl)acetyl]-9-[(1-methyl-3-piperidinyl)methoxy]-7-(5-methyl-2-thienyl)-2,3,4,5-tetrahydro-1,4-benzoxazepine (1), which was identified through a previously reported high-throughput phenotypic screen. The analogue series was designed, synthesized, and evaluated for antileishmanial activity to establish pharmacophore elements and preliminary structure-activity relationships as key steps in validating the series for further optimization. This study led to identification of the early lead compound 46, which exhibited sub-micromolar proliferation inhibitory activity against intra-macrophage L. mexicana amastigotes, modest selectivity towards host macrophages (J774A.1 line), and good aqueous solubility.","journal":"Bioorganic & Medicinal Chemistry Letters","year":2024,"id":449487,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9412,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":446507,"name":"Stefan Kwiatkowski","orcid":null,"position":1,"is_corresponding":false},{"id":758717,"name":"Diana Ortiz","orcid":"0000-0001-6492-8842","position":2,"is_corresponding":false},{"id":1090129,"name":"Gaurav Shoeran","orcid":null,"position":3,"is_corresponding":false},{"id":588925,"name":"Jared T. Hammill","orcid":"0000-0002-9463-0526","position":4,"is_corresponding":false},{"id":759220,"name":"Ho Shin Kim","orcid":null,"position":5,"is_corresponding":false},{"id":1269771,"name":"Joanna Cholewo","orcid":null,"position":6,"is_corresponding":false},{"id":392090,"name":"Scott M. Landfear","orcid":"0000-0002-1643-6664","position":7,"is_corresponding":false},{"id":464227,"name":"R. Kiplin Guy","orcid":"0000-0002-9638-2060","position":8,"is_corresponding":false},{"id":1089670,"name":"Tara Man Kadayat","orcid":"0000-0002-7615-436X","position":0,"is_corresponding":true}],"reference_count":22,"raw_metadata":null,"created_at":"2026-07-19T02:02:20.585759Z","pmid":"39477128","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":[]}