{"id":"https://openalex.org/W1990983167","doi":"https://doi.org/10.1021/jm049448r","title":"2,4,6-Trisubstituted Pyrimidines as a New Class of Selective Adenosine A 1 Receptor Antagonists","display_name":"2,4,6-Trisubstituted Pyrimidines as a New Class of Selective Adenosine A 1 Receptor Antagonists","publication_year":2004,"publication_date":"2004-11-13","ids":{"openalex":"https://openalex.org/W1990983167","doi":"https://doi.org/10.1021/jm049448r","mag":"1990983167","pmid":"https://pubmed.ncbi.nlm.nih.gov/15588088"},"language":"en","primary_location":{"id":"doi:10.1021/jm049448r","doi":"https://doi.org/10.1021/jm049448r","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm049448r","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/A5040712499","display_name":"Lisa C. W. Chang","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Lisa C. W. Chang","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5049689426","display_name":"Ronald F. Spanjersberg","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Ronald F. Spanjersberg","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5065703230","display_name":"Jacobien K. von Frijtag Drabbe K\u00fcnzel","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Jacobien K. von Frijtag Drabbe K\u00fcnzel","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110009618","display_name":"Thea Mulder\u2010Krieger","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Thea Mulder-Krieger","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5007657550","display_name":"Gijs van den Hout","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Gijs van den Hout","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5011108152","display_name":"Margot W. Beukers","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Margot W. Beukers","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5076010654","display_name":"Johannes Brussee","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Johannes Brussee","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5065525958","display_name":"Adriaan P. IJzerman","orcid":"https://orcid.org/0000-0002-1182-2259","observed_orcids":["https://orcid.org/0000-0002-1182-2259"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Adriaan P. IJzerman","raw_affiliation_strings":["Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Division of Medicinal Chemistry, Leiden/Amsterdam Center for Drug Research, P.O. Box 9502, 2300 RA Leiden, The Netherlands","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5065525958"],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":1.3317,"has_fulltext":false,"cited_by_count":102,"citation_normalized_percentile":{"value":0.72504798,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":88,"max":99},"biblio":{"volume":"47","issue":"26","first_page":"6529","last_page":"6540"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T11193","display_name":"Adenosine and Purinergic Signaling","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1314","display_name":"Physiology"},"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"}},"topics":[{"id":"https://openalex.org/T11193","display_name":"Adenosine and Purinergic Signaling","score":0.9994999766349792,"subfield":{"id":"https://openalex.org/subfields/1314","display_name":"Physiology"},"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"}},{"id":"https://openalex.org/T10211","display_name":"Computational Drug Discovery Methods","score":9.999999747378752e-05,"subfield":{"id":"https://openalex.org/subfields/3002","display_name":"Drug Discovery"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T12827","display_name":"Biochemical and Molecular Research","score":9.999999747378752e-05,"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/adenosine-a1-receptor-antagonist","display_name":"adenosine A1 receptor antagonist","score":0.9380000233650208},{"id":"https://openalex.org/keywords/pharmacophore","display_name":"pharmacophore","score":0.7509999871253967},{"id":"https://openalex.org/keywords/polar-surface-area","display_name":"polar surface area","score":0.9470000267028809},{"id":"https://openalex.org/keywords/cns-drug-candidates","display_name":"CNS drug candidates","score":0.5360000133514404},{"id":"https://openalex.org/keywords/adenosine-receptor-selectivity","display_name":"adenosine receptor selectivity","score":0.9160000085830688},{"id":"https://openalex.org/keywords/molecular-modeling","display_name":"molecular modeling","score":0.5180000066757202},{"id":"https://openalex.org/keywords/heterocycle-synthesis","display_name":"heterocyclic synthesis","score":0.4909999966621399}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.9375208616256714},{"id":"https://openalex.org/C2776991684","wikidata":"https://www.wikidata.org/wiki/Q190012","display_name":"Adenosine","level":2,"score":0.5876128673553467},{"id":"https://openalex.org/C67907053","wikidata":"https://www.wikidata.org/wiki/Q356147","display_name":"Adenosine receptor","level":4,"score":0.5835093259811401},{"id":"https://openalex.org/C2777212361","wikidata":"https://www.wikidata.org/wiki/Q5127848","display_name":"Class (philosophy)","level":2,"score":0.47093382477760315},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.43061143159866333},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.43015575408935547},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.3875386714935303},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.36779192090034485},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.32276275753974915},{"id":"https://openalex.org/C2778938600","wikidata":"https://www.wikidata.org/wiki/Q389934","display_name":"Agonist","level":3,"score":0.08993446826934814},{"id":"https://openalex.org/C154945302","wikidata":"https://www.wikidata.org/wiki/Q11660","display_name":"Artificial intelligence","level":1,"score":0.05473208427429199},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.0},{"id":"https://openalex.org/C41008148","wikidata":"https://www.wikidata.org/wiki/Q21198","display_name":"Computer science","level":0,"score":0.0}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001667","descriptor_name":"Binding, Competitive","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D002460","descriptor_name":"Cell Line","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003412","descriptor_name":"Cricetulus","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006224","descriptor_name":"Cricetinae","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":"D008024","descriptor_name":"Ligands","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008958","descriptor_name":"Models, Molecular","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":true},{"descriptor_ui":"D011744","descriptor_name":"Pyrimidinones","qualifier_ui":"Q000494","qualifier_name":"pharmacology","is_major_topic":false},{"descriptor_ui":"D011744","descriptor_name":"Pyrimidinones","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011869","descriptor_name":"Radioligand Assay","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013329","descriptor_name":"Structure-Activity Relationship","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D043684","descriptor_name":"Receptor, Adenosine A3","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D043705","descriptor_name":"Receptor, Adenosine A2A","qualifier_ui":"Q000187","qualifier_name":"drug effects","is_major_topic":false},{"descriptor_ui":"D058916","descriptor_name":"Adenosine A1 Receptor Antagonists","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true}],"locations_count":2,"locations":[{"id":"doi:10.1021/jm049448r","doi":"https://doi.org/10.1021/jm049448r","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm049448r","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:15588088","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/15588088","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","score":0.46810001134872437,"display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":26,"referenced_works":["https://openalex.org/W1973303477","https://openalex.org/W1975161148","https://openalex.org/W1978533215","https://openalex.org/W1979643910","https://openalex.org/W1982891404","https://openalex.org/W1986567043","https://openalex.org/W1990057891","https://openalex.org/W1991465998","https://openalex.org/W1994952134","https://openalex.org/W2013112092","https://openalex.org/W2013898257","https://openalex.org/W2016775717","https://openalex.org/W2027838903","https://openalex.org/W2033413891","https://openalex.org/W2035830147","https://openalex.org/W2037385935","https://openalex.org/W2060101960","https://openalex.org/W2080008373","https://openalex.org/W2093356686","https://openalex.org/W2126305917","https://openalex.org/W2151238743","https://openalex.org/W2167762355","https://openalex.org/W2182593958","https://openalex.org/W2951965616","https://openalex.org/W4248107770","https://openalex.org/W4249877820"],"related_works":["https://openalex.org/W1964407556","https://openalex.org/W2040740996","https://openalex.org/W2084274926","https://openalex.org/W2952786627","https://openalex.org/W2169770305","https://openalex.org/W2027187762","https://openalex.org/W2527163109","https://openalex.org/W4388288148","https://openalex.org/W2888047260","https://openalex.org/W2006182889"],"abstract_inverted_index":{"Adenosine":[0],"receptor":[1,37,94],"antagonists":[2],"usually":[3],"possess":[4],"a":[5,31,39,48,57,68,134],"bi-":[6],"or":[7,116],"tricyclic":[8],"heteroaromatic":[9],"structure":[10],"at":[11,62,90,126],"their":[12],"core":[13,50],"with":[14],"varying":[15],"substitution":[16],"patterns":[17],"to":[18,71],"achieve":[19,56],"selectivity":[20,114],"and/or":[21],"greater":[22],"affinity.":[23],"Taking":[24],"into":[25],"account":[26],"molecular":[27],"modeling":[28],"results":[29],"from":[30,43],"series":[32,84],"of":[33,85,119,123,137],"potent":[34],"adenosine":[35,92,130],"A1":[36,93,107],"antagonists,":[38],"pharmacophore":[40],"was":[41],"derived":[42],"which":[44],"we":[45,65,79],"show":[46],"that":[47,59],"monocyclic":[49],"can":[51],"be":[52],"equally":[53],"effective.":[54],"To":[55],"compound":[58,101],"may":[60],"act":[61],"the":[63,91,124,127],"CNS":[64],"propose":[66],"imposing":[67],"restriction":[69],"related":[70],"its":[72],"polar":[73],"surface":[74],"area":[75],"(PSA).":[76],"In":[77,99],"consequence,":[78],"have":[80],"synthesized":[81],"two":[82],"novel":[83],"pyrimidines,":[86],"possessing":[87],"good":[88],"potency":[89],"and":[95,113,132],"desirable":[96],"PSA":[97,135],"values.":[98],"particular,":[100],"30":[102],"(LUF":[103],"5735)":[104],"displays":[105],"excellent":[106],"affinity":[108],"(Ki":[109],"=":[110],"4":[111],"nM)":[112],"(<":[115],"=50%":[117],"displacement":[118],"1":[120],"muM":[121],"concentrations":[122],"radioligand":[125],"other":[128],"three":[129],"receptors)":[131],"has":[133],"value":[136],"53":[138],"A2.":[139]},"counts_by_year":[{"year":2026,"cited_by_count":5},{"year":2025,"cited_by_count":4},{"year":2024,"cited_by_count":1},{"year":2023,"cited_by_count":5},{"year":2022,"cited_by_count":2},{"year":2021,"cited_by_count":2},{"year":2020,"cited_by_count":1},{"year":2019,"cited_by_count":5},{"year":2018,"cited_by_count":4},{"year":2017,"cited_by_count":7},{"year":2016,"cited_by_count":8},{"year":2015,"cited_by_count":2},{"year":2014,"cited_by_count":7},{"year":2013,"cited_by_count":8},{"year":2012,"cited_by_count":8}],"updated_date":"2026-11-07T11:25:07.637180","created_date":"2016-06-24T00:00:00"}