{"doi":"10.1002/9781118739907.ch7","title":"ENZYMATICALLY ACTIVATED PHOSPHATE AND PHOSPHONATE PRODRUGS","abstract":null,"journal":"Enzyme Technologies","year":2013,"id":686101,"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":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":452556,"name":"Charles E. McKenna","orcid":"0000-0002-3540-6663","position":1,"is_corresponding":false},{"id":1792507,"name":"Ivan S. Krylov","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ENZYMATICALLY ACTIVATED PHOSPHATE AND PHOSPHONATE PRODRUGS","abstract":"This chapter surveys several representative examples of current prodrug approaches which explicitly depend on enzyme-mediated activation. The chapter discusses several phosphoramidate prodrugs that have reached clinical trials. The phosphoramidate prodrug approach can enhance intracellular delivery of nucleotide analogs and has proven to increase activity of a number of antiviral or anticancer nucleosides. The lipidic prodrug approach – improvement of parent drug's hydrophobicity via incorporation into its structure of a biolabile lipophilic alkyl chain – has been known for decades and has been applied to a number of nucleotide analogs. The (S)-acyl-2-thioethyl (SATE) approach has been applied to a number of nucleoside monophosphate/ phosphonate analogs to create corresponding SATE pronucleotides that exhibit in vitro antiviral activity in both wild-type and thymidine kinase (TK)-deficient cell lines. Prodrug design continues to be one of the most important approaches in the medicinal chemistry armamentarium in improving undesirable pharmacokinetic (PK) properties of drugs.","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26207759","pmcid":null,"openalex_id":"https://openalex.org/W1556076960","authors":[],"funders":[],"total_grants":0,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"closed","license":"http://doi.wiley.com/10.1002/tdm_license_1.1","oa_locations":[{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1002/9781118739907.ch7","host_type":"publisher"},{"url":"https://doi.org/10.1002/9781118739907.ch7","host_type":""}],"fields_of_study":["HIV/AIDS drug development and treatment","Biochemical and Molecular Research","Click Chemistry and Applications"],"mesh_terms":[],"keywords":["Prodrug","Phosphoramidate","Phosphonate","Nucleotide","Chemistry","Nucleoside","Combinatorial chemistry","Drug","Thymidine kinase","Biochemistry","Stereochemistry","Pharmacology","Biology","Virus","Herpes simplex virus","Virology"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Zero hunger"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T18:32:25.355814Z","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":[]}