{"id":"https://openalex.org/W2074956847","doi":"https://doi.org/10.1021/jm060854f","title":"4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species","display_name":"4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species","publication_year":2006,"publication_date":"2006-10-25","ids":{"openalex":"https://openalex.org/W2074956847","doi":"https://doi.org/10.1021/jm060854f","mag":"2074956847","pmid":"https://pubmed.ncbi.nlm.nih.gov/17154493"},"language":"en","primary_location":{"id":"doi:10.1021/jm060854f","doi":"https://doi.org/10.1021/jm060854f","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm060854f","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Medicinal Chemistry","raw_type":"journal-article"},"volume":null,"type":"article","is_traditional":true,"indexed_in":["crossref","pubmed"],"open_access":{"is_oa":false,"oa_status":"closed","oa_url":null,"any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5044099332","display_name":"Vincenzo Summa","orcid":"https://orcid.org/0000-0002-6288-2681","observed_orcids":["https://orcid.org/0000-0002-6288-2681"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Vincenzo Summa","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036690484","display_name":"Alessia Petrocchi","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Alessia Petrocchi","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5063815988","display_name":"Victor G. Matassa","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Victor G. Matassa","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5073858751","display_name":"Cristina Gardelli","orcid":"https://orcid.org/0000-0003-1169-2180","observed_orcids":["https://orcid.org/0000-0003-1169-2180"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Cristina Gardelli","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5059883181","display_name":"Ester Muraglia","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ester Muraglia","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5060422552","display_name":"Michael Rowley","orcid":"https://orcid.org/0000-0003-2672-1255","observed_orcids":["https://orcid.org/0000-0003-2672-1255"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michael Rowley","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5112913341","display_name":"Odalys Gonzalez Paz","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Odalys Gonzalez Paz","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5111594821","display_name":"Ralph Laufer","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ralph Laufer","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5036851868","display_name":"Edith S. Monteagudo","orcid":"https://orcid.org/0000-0003-2471-5695","observed_orcids":["https://orcid.org/0000-0003-2471-5695"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Edith Monteagudo","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5013062348","display_name":"Paola Pace","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Paola Pace","raw_affiliation_strings":["Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Departments of Medicinal Chemistry and Drug Metabolism IRBM-MRL Rome, Via Pontina, Km 30.600, 00040 Pomezia, Rome, Italy","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":6.3627,"has_fulltext":false,"cited_by_count":104,"citation_normalized_percentile":{"value":0.97035099,"is_in_top_1_percent":false,"is_in_top_10_percent":true},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"49","issue":"23","first_page":"6646","last_page":"6649"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10526","display_name":"HIV/AIDS drug development and treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10526","display_name":"HIV/AIDS drug development and treatment","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/2725","display_name":"Infectious Diseases"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10112","display_name":"HIV Research and Treatment","score":0.00019999999494757503,"subfield":{"id":"https://openalex.org/subfields/2406","display_name":"Virology"},"field":{"id":"https://openalex.org/fields/24","display_name":"Immunology and Microbiology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11845","display_name":"Cancer therapeutics and mechanisms","score":0.0,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/hiv-integrase-inhibitors","display_name":"HIV integrase inhibitors","score":0.9959999918937683},{"id":"https://openalex.org/keywords/integrase-strand-transfer-inhibitors","display_name":"integrase strand transfer inhibitors","score":0.8650000095367432},{"id":"https://openalex.org/keywords/antiretroviral-drug-discovery","display_name":"antiretroviral drug discovery","score":0.8949999809265137},{"id":"https://openalex.org/keywords/pharmacokinetics","display_name":"pharmacokinetics","score":0.8240000009536743}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.8762768507003784},{"id":"https://openalex.org/C112705442","wikidata":"https://www.wikidata.org/wiki/Q323936","display_name":"Pharmacokinetics","level":2,"score":0.8713551759719849},{"id":"https://openalex.org/C14430832","wikidata":"https://www.wikidata.org/wiki/Q412550","display_name":"Integrase","level":3,"score":0.8306041955947876},{"id":"https://openalex.org/C57992300","wikidata":"https://www.wikidata.org/wiki/Q2066956","display_name":"Potency","level":3,"score":0.6990893483161926},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.6284478902816772},{"id":"https://openalex.org/C2778327999","wikidata":"https://www.wikidata.org/wiki/Q188777","display_name":"Carboxamide","level":2,"score":0.6282532811164856},{"id":"https://openalex.org/C2777302000","wikidata":"https://www.wikidata.org/wiki/Q412251","display_name":"Integrase inhibitor","level":5,"score":0.5184338092803955},{"id":"https://openalex.org/C3013748606","wikidata":"https://www.wikidata.org/wiki/Q15787","display_name":"Human immunodeficiency virus (HIV)","level":2,"score":0.4729421138763428},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.40781307220458984},{"id":"https://openalex.org/C202751555","wikidata":"https://www.wikidata.org/wiki/Q221681","display_name":"In vitro","level":2,"score":0.31602102518081665},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.3129737973213196},{"id":"https://openalex.org/C159047783","wikidata":"https://www.wikidata.org/wiki/Q7215","display_name":"Virology","level":1,"score":0.16115838289260864},{"id":"https://openalex.org/C2993143319","wikidata":"https://www.wikidata.org/wiki/Q583050","display_name":"Antiretroviral therapy","level":4,"score":0.11920741200447083},{"id":"https://openalex.org/C142462285","wikidata":"https://www.wikidata.org/wiki/Q2528140","display_name":"Viral load","level":3,"score":0.07594543695449829},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.07153716683387756},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.062049418687820435}],"mesh":[{"descriptor_ui":"D000284","descriptor_name":"Administration, Oral","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000577","descriptor_name":"Amides","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D000577","descriptor_name":"Amides","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D000577","descriptor_name":"Amides","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001682","descriptor_name":"Biological Availability","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D004285","descriptor_name":"Dogs","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006801","descriptor_name":"Humans","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008253","descriptor_name":"Macaca mulatta","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011743","descriptor_name":"Pyrimidines","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D011743","descriptor_name":"Pyrimidines","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D011743","descriptor_name":"Pyrimidines","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011744","descriptor_name":"Pyrimidinones","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":false},{"descriptor_ui":"D011744","descriptor_name":"Pyrimidinones","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D011744","descriptor_name":"Pyrimidinones","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D014779","descriptor_name":"Virus Replication","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015497","descriptor_name":"HIV-1","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D019428","descriptor_name":"HIV Integrase Inhibitors","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D019428","descriptor_name":"HIV Integrase Inhibitors","qualifier_ui":"Q000493","qualifier_name":"pharmacokinetics","is_major_topic":false},{"descriptor_ui":"D019428","descriptor_name":"HIV Integrase Inhibitors","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D044967","descriptor_name":"Serum","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D066298","descriptor_name":"In Vitro Techniques","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/jm060854f","doi":"https://doi.org/10.1021/jm060854f","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm060854f","pdf_url":null,"source":{"id":"https://openalex.org/S162030435","display_name":"Journal of Medicinal Chemistry","issn_l":"0022-2623","issn":["0022-2623","1520-4804"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["anvur-scientific","cwts-core","dongbi-a","jufo-3","ki-jl-2","medline","norway-2","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310320006","host_organization_name":"American Chemical Society","host_organization_lineage":["https://openalex.org/P4310320006"],"host_organization_lineage_names":["American Chemical Society"],"type":"journal"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of Medicinal Chemistry","raw_type":"journal-article"},{"id":"pmid:17154493","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/17154493","pdf_url":null,"source":{"id":"https://openalex.org/S4306525036","display_name":"PubMed","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1299303238","host_organization_name":"National Institutes of Health","host_organization_lineage":["https://openalex.org/I1299303238"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"publishedVersion","is_accepted":true,"is_published":true,"raw_source_name":"Journal of medicinal chemistry","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.9074000120162964}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":11,"referenced_works":["https://openalex.org/W2001111303","https://openalex.org/W2003803262","https://openalex.org/W2025444624","https://openalex.org/W2071546427","https://openalex.org/W2087519172","https://openalex.org/W2117959947","https://openalex.org/W2132185205","https://openalex.org/W2151389386","https://openalex.org/W2156927215","https://openalex.org/W2167278859","https://openalex.org/W2171711893"],"related_works":["https://openalex.org/W2059458343","https://openalex.org/W2063889189","https://openalex.org/W2086295635","https://openalex.org/W2072692397","https://openalex.org/W7120537496","https://openalex.org/W2059248686","https://openalex.org/W2063240078","https://openalex.org/W2056312737","https://openalex.org/W2056676492","https://openalex.org/W2010916331"],"abstract_inverted_index":{"The":[0,16],"dihydroxypyrimidine":[1,33],"carboxamide":[2],"4a":[3],"was":[4],"discovered":[5],"as":[6],"a":[7],"potent":[8],"and":[9,23,35,59],"selective":[10],"HIV":[11,48],"integrase":[12],"strand":[13],"transfer":[14],"inhibitor.":[15],"optimization":[17],"of":[18,29,54],"physicochemical":[19],"properties,":[20],"pharmacokinetic":[21],"profiles,":[22],"potency":[24],"led":[25],"to":[26],"the":[27,32,38,46,52],"identification":[28],"13":[30],"in":[31,37,45,51,63],"series":[34,40],"18":[36],"N-methylpyrimidinone":[39],"having":[41],"low":[42],"nanomolar":[43],"activity":[44],"cellular":[47],"spread":[49],"assay":[50],"presence":[53],"50%":[55],"normal":[56],"human":[57],"serum":[58],"very":[60],"good":[61],"pharmacokinetics":[62],"preclinical":[64],"species.":[65]},"counts_by_year":[{"year":2026,"cited_by_count":3},{"year":2025,"cited_by_count":1},{"year":2024,"cited_by_count":2},{"year":2023,"cited_by_count":3},{"year":2022,"cited_by_count":3},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":4},{"year":2019,"cited_by_count":1},{"year":2018,"cited_by_count":7},{"year":2017,"cited_by_count":2},{"year":2016,"cited_by_count":4},{"year":2015,"cited_by_count":6},{"year":2014,"cited_by_count":6},{"year":2013,"cited_by_count":7},{"year":2012,"cited_by_count":9}],"updated_date":"2026-11-03T10:50:19.383937","created_date":"2016-06-24T00:00:00"}
