{"id":"https://openalex.org/W2093281114","doi":"https://doi.org/10.1021/tx034021t","title":"Synthesis of Stereospecifically Deuterated 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) Diastereomers and Metabolism by A/J Mouse Lung Microsomes and Cytochrome P450 2A5","display_name":"Synthesis of Stereospecifically Deuterated 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) Diastereomers and Metabolism by A/J Mouse Lung Microsomes and Cytochrome P450 2A5","publication_year":2003,"publication_date":"2003-05-20","ids":{"openalex":"https://openalex.org/W2093281114","doi":"https://doi.org/10.1021/tx034021t","mag":"2093281114","pmid":"https://pubmed.ncbi.nlm.nih.gov/12807362"},"language":"en","primary_location":{"id":"doi:10.1021/tx034021t","doi":"https://doi.org/10.1021/tx034021t","is_oa":false,"landing_page_url":"https://doi.org/10.1021/tx034021t","pdf_url":null,"source":{"id":"https://openalex.org/S152840809","display_name":"Chemical Research in Toxicology","issn_l":"0893-228X","issn":["0893-228X","1520-5010"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","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":"Chemical Research in Toxicology","raw_type":"journal-article"},"volume":null,"type":"article","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/A5052879451","display_name":"John R. Jalas","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I130238516","display_name":"University of Minnesota","ror":"https://ror.org/017zqws13","country_code":"US","type":"education","lineage":["https://openalex.org/I130238516"]},{"id":"https://openalex.org/I4390039358","display_name":"Masonic Cancer Center","ror":"https://ror.org/05x083d20","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I130238516","https://openalex.org/I4390039358"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"John R. Jalas","raw_affiliation_strings":["Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, and Cancer Center, University of Minnesota, MMC 806, 420 Delaware Street SE, Minneapolis, Minnesota 55455"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, and Cancer Center, University of Minnesota, MMC 806, 420 Delaware Street SE, Minneapolis, Minnesota 55455","institution_ids":["https://openalex.org/I130238516","https://openalex.org/I4390039358"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5033402104","display_name":"Stephen S. Hecht","orcid":"https://orcid.org/0000-0001-7228-1356","observed_orcids":["https://orcid.org/0000-0001-7228-1356"]},"institutions":[{"id":"https://openalex.org/I130238516","display_name":"University of Minnesota","ror":"https://ror.org/017zqws13","country_code":"US","type":"education","lineage":["https://openalex.org/I130238516"]},{"id":"https://openalex.org/I4390039358","display_name":"Masonic Cancer Center","ror":"https://ror.org/05x083d20","country_code":"US","type":"healthcare","lineage":["https://openalex.org/I130238516","https://openalex.org/I4390039358"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Stephen S. Hecht","raw_affiliation_strings":["Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, and Cancer Center, University of Minnesota, MMC 806, 420 Delaware Street SE, Minneapolis, Minnesota 55455"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Chemistry, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, and Cancer Center, University of Minnesota, MMC 806, 420 Delaware Street SE, Minneapolis, Minnesota 55455","institution_ids":["https://openalex.org/I130238516","https://openalex.org/I4390039358"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":["https://openalex.org/A5033402104"],"corresponding_institution_ids":["https://openalex.org/I130238516","https://openalex.org/I4390039358"],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":1.0904,"has_fulltext":false,"cited_by_count":13,"citation_normalized_percentile":{"value":0.70621931,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":95},"biblio":{"volume":"16","issue":"6","first_page":"782","last_page":"793"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13561","display_name":"Chemical Reactions and Isotopes","score":0.41769999265670776,"subfield":{"id":"https://openalex.org/subfields/3003","display_name":"Pharmaceutical Science"},"field":{"id":"https://openalex.org/fields/30","display_name":"Pharmacology, Toxicology and Pharmaceutics"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T13561","display_name":"Chemical Reactions and Isotopes","score":0.41769999265670776,"subfield":{"id":"https://openalex.org/subfields/3003","display_name":"Pharmaceutical Science"},"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/T10375","display_name":"Pharmacogenetics and Drug Metabolism","score":0.24050000309944153,"subfield":{"id":"https://openalex.org/subfields/3004","display_name":"Pharmacology"},"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/T10433","display_name":"Carcinogens and Genotoxicity Assessment","score":0.11720000207424164,"subfield":{"id":"https://openalex.org/subfields/1306","display_name":"Cancer Research"},"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/nnal","display_name":"NNAL","score":0.7990000247955322},{"id":"https://openalex.org/keywords/nnk","display_name":"NNK","score":0.781000018119812},{"id":"https://openalex.org/keywords/tobacco-specific-nitrosamines","display_name":"tobacco-specific nitrosamines","score":0.7900000214576721},{"id":"https://openalex.org/keywords/stereospecific-metabolism","display_name":"stereospecific metabolism","score":0.7509999871253967},{"id":"https://openalex.org/keywords/lung-microsomes","display_name":"lung microsomes","score":0.8270000219345093},{"id":"https://openalex.org/keywords/o6-methylguanine","display_name":"O6-methylguanine","score":0.7950000166893005},{"id":"https://openalex.org/keywords/dna-adducts","display_name":"DNA adducts","score":0.777999997138977},{"id":"https://openalex.org/keywords/regioselectivity","display_name":"regioselectivity","score":0.7319999933242798},{"id":"https://openalex.org/keywords/n-methylation","display_name":"N-methylation","score":0.6570000052452087},{"id":"https://openalex.org/keywords/hydroxylation","display_name":"hydroxylation","score":0.5600000023841858}],"concepts":[{"id":"https://openalex.org/C114246631","wikidata":"https://www.wikidata.org/wiki/Q187661","display_name":"Carcinogen","level":2,"score":0.807244062423706},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.8016378879547119},{"id":"https://openalex.org/C526171541","wikidata":"https://www.wikidata.org/wiki/Q407693","display_name":"Cytochrome P450","level":3,"score":0.6815133690834045},{"id":"https://openalex.org/C87644729","wikidata":"https://www.wikidata.org/wiki/Q547502","display_name":"Microsome","level":3,"score":0.6241456270217896},{"id":"https://openalex.org/C62231903","wikidata":"https://www.wikidata.org/wiki/Q1057","display_name":"Metabolism","level":2,"score":0.5990089774131775},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.5208593010902405},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.47388309240341187},{"id":"https://openalex.org/C2781109383","wikidata":"https://www.wikidata.org/wiki/Q898497","display_name":"Hydroxylation","level":3,"score":0.4731869697570801},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.23780816793441772}],"mesh":[{"descriptor_ui":"D000072467","descriptor_name":"Cytochrome P450 Family 2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001189","descriptor_name":"Aryl Hydrocarbon Hydroxylases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D005260","descriptor_name":"Female","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D006899","descriptor_name":"Mixed Function Oxygenases","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D006900","descriptor_name":"Hydroxylation","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008168","descriptor_name":"Lung","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":true},{"descriptor_ui":"D008805","descriptor_name":"Mice, Inbred A","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D008861","descriptor_name":"Microsomes","qualifier_ui":"Q000201","qualifier_name":"enzymology","is_major_topic":true},{"descriptor_ui":"D009602","descriptor_name":"Nitrosamines","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D009602","descriptor_name":"Nitrosamines","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D009602","descriptor_name":"Nitrosamines","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D009682","descriptor_name":"Magnetic Resonance Spectroscopy","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013237","descriptor_name":"Stereoisomerism","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D013379","descriptor_name":"Substrate Specificity","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D015394","descriptor_name":"Molecular Structure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D051379","descriptor_name":"Mice","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D065637","descriptor_name":"Cytochrome P-450 CYP2A6","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/tx034021t","doi":"https://doi.org/10.1021/tx034021t","is_oa":false,"landing_page_url":"https://doi.org/10.1021/tx034021t","pdf_url":null,"source":{"id":"https://openalex.org/S152840809","display_name":"Chemical Research in Toxicology","issn_l":"0893-228X","issn":["0893-228X","1520-5010"],"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core","dongbi-b","doyens","jufo-2","ki-jl-1","medline","norway-1","poland-100","russia-white-list-2","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":"Chemical Research in Toxicology","raw_type":"journal-article"},{"id":"pmid:12807362","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/12807362","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":"Chemical research in toxicology","raw_type":"Journal Article"}],"best_oa_location":null,"sustainable_development_goals":[{"display_name":"Good health and well-being","score":0.8371999859809875,"id":"https://metadata.un.org/sdg/3"}],"study_designs":[],"awards":[{"id":"https://openalex.org/G1959846446","display_name":null,"funder_award_id":"CA81301","funder_id":"https://openalex.org/F4320337351","funder_display_name":"National Cancer Institute"}],"funders":[{"id":"https://openalex.org/F4320337351","display_name":"National Cancer Institute","ror":"https://ror.org/040gcmg81"}],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":13,"referenced_works":["https://openalex.org/W1608644315","https://openalex.org/W1774462230","https://openalex.org/W1982685986","https://openalex.org/W1989550448","https://openalex.org/W1996814402","https://openalex.org/W2010871897","https://openalex.org/W2049158232","https://openalex.org/W2051639214","https://openalex.org/W2101324933","https://openalex.org/W2107803449","https://openalex.org/W2115470051","https://openalex.org/W2148788078","https://openalex.org/W2150743675"],"related_works":["https://openalex.org/W2118336444","https://openalex.org/W2049158232","https://openalex.org/W2132881333","https://openalex.org/W1930919448","https://openalex.org/W1545187120","https://openalex.org/W2115071169","https://openalex.org/W2002884812","https://openalex.org/W2107803449","https://openalex.org/W2110026173","https://openalex.org/W1553912543"],"abstract_inverted_index":{"The":[0,130,181,262],"tobacco-specific":[1],"nitrosamine":[2],"4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone":[3],"(NNK)":[4],"is":[5,14,30,41],"a":[6,15],"lung":[7,18,142,169,195],"carcinogen":[8],"in":[9,37,87,131,161,267],"mice":[10],"and":[11,13,67,102,115,126,144],"rats":[12],"putative":[16],"human":[17],"carcinogen.":[19],"NNK":[20,47,66,249],"undergoes":[21],"cytochrome":[22,148],"p450-mediated":[23],"metabolic":[24,54],"activation":[25,55,61],"to":[26,34,85,95,185,227],"DNA-binding":[27],"intermediates":[28],"but":[29,174,201,231],"also":[31,42],"extensively":[32],"reduced":[33],"4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol":[35],"(NNAL)":[36],"vivo.":[38],"Because":[39],"NNAL":[40,68,101,274],"tumorigenic,":[43],"the":[44,53,70,73,79,88,98,103,112,119,159,162,177,192,228,246,270],"carcinogenicity":[45],"of":[46,56,62,65,81,100,105,134,164,179,183,198,248,264,273],"may":[48],"actually":[49],"be":[50],"governed":[51],"by":[52,167],"NNAL,":[57],"rather":[58],"than":[59,209,258],"direct":[60],"NNK.":[63],"Metabolism":[64],"at":[69,111,158,253],"4-position":[71,160],"generates":[72],"same":[74],"critical":[75],"DNA":[76],"lesion,":[77],"O(6)-methylguanine,":[78],"levels":[80],"which":[82],"are":[83,275],"correlated":[84],"tumorigenicity":[86],"A/J":[89,140,193],"mouse":[90,141,147,168,194],"model.":[91],"In":[92],"an":[93],"effort":[94],"better":[96],"understand":[97],"bioactivation":[99],"effect":[104],"carbinol-carbon":[106],"stereochemistry":[107,152,226],"on":[108],"prochiral":[109],"selectivity":[110],"4-position,":[113],"(R)-":[114],"(S)-NNAL,":[116],"along":[117],"with":[118,224,239],"stereospecifically":[120],"4-deuterated":[121],"diastereomers":[122],"(1R,4R)-[4-(2)H(1)]NNAL,":[123],"(1R,4S)-[4-(2)H(1)]NNAL,":[124],"(1S,4R)-[4-(2)H(1)]NNAL,":[125],"(1S,4S)-[4-(2)H(1)]NNAL,":[127],"were":[128],"synthesized.":[129],"vitro":[132],"metabolism":[133,163,197,268],"these":[135,165,265],"compounds":[136,166],"was":[137,188,204,217,234],"investigated":[138],"using":[139],"microsomes":[143,170],"Spodoptera":[145],"frugiperda-expressed":[146],"p450":[149,172,215,220,243],"2A5.":[150],"Carbinol-carbon":[151],"did":[153,175],"not":[154,235],"appreciably":[155],"influence":[156,176],"stereoselectivity":[157],"or":[171],"2A5":[173,216,221,244],"regiochemistry":[178],"metabolism.":[180],"ratio":[182,203],"4-":[184],"N-methyl":[186],"hydroxylation":[187],"approximately":[189],"1:1":[190],"for":[191,206,210,269],"microsome-mediated":[196],"all":[199],"substrates,":[200],"this":[202,232],"higher":[205],"(1S)":[207,225,251],"substrates":[208,223,238,252],"their":[211],"(1R)":[212,240,260],"counterparts":[213],"when":[214],"used.":[218],"Interestingly,":[219],"converted":[222],"respective":[229],"N-oxides,":[230],"metabolite":[233],"formed":[236],"from":[237,250,259],"stereochemistry.":[241],"Furthermore,":[242],"catalyzed":[245],"formation":[247],"significantly":[254],"greater":[255],"maximal":[256],"rates":[257],"substrates.":[261],"implications":[263],"differences":[266],"tumorigenic":[271],"mechanism":[272],"discussed.":[276]},"counts_by_year":[{"year":2022,"cited_by_count":2},{"year":2015,"cited_by_count":1},{"year":2013,"cited_by_count":1}],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}