{"id":"https://openalex.org/W1978739068","doi":"https://doi.org/10.1021/jm00173a030","title":"Synthesis and evaluation of N-substituted cis-N-methyl-2-(1-pyrrolidinyl)cyclohexylamines as high affinity .sigma. receptor ligands. Identification of a new class of highly potent and selective .sigma. receptor probes","display_name":"Synthesis and evaluation of N-substituted cis-N-methyl-2-(1-pyrrolidinyl)cyclohexylamines as high affinity .sigma. receptor ligands. Identification of a new class of highly potent and selective .sigma. receptor probes","publication_year":1990,"publication_date":"1990-11-01","ids":{"openalex":"https://openalex.org/W1978739068","doi":"https://doi.org/10.1021/jm00173a030","mag":"1978739068","pmid":"https://pubmed.ncbi.nlm.nih.gov/2172538"},"language":"en","primary_location":{"id":"doi:10.1021/jm00173a030","doi":"https://doi.org/10.1021/jm00173a030","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm00173a030","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","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/A5111733325","display_name":"Brian R. de Costa","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1299303238","display_name":"National Institutes of Health","ror":"https://ror.org/01cwqze88","country_code":"US","type":"government","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238"]},{"id":"https://openalex.org/I4210090567","display_name":"National Institute of Diabetes and Digestive and Kidney Diseases","ror":"https://ror.org/00adh9b73","country_code":"US","type":"facility","lineage":["https://openalex.org/I1299022934","https://openalex.org/I1299303238","https://openalex.org/I4210090567"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Brian R. De Costa","raw_affiliation_strings":["Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Laboratory of Medicinal Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892","institution_ids":["https://openalex.org/I1299303238","https://openalex.org/I4210090567"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5109400840","display_name":"Wayne D. Bowen","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Wayne D. Bowen","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110618612","display_name":"Andrew Thurkauf","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Andrew Thurkauf","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5113535001","display_name":"Daniel T. Finn","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Daniel T. Finn","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5106826522","display_name":"Sondra Vazirani","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Sondra Vazirani","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5103446078","display_name":"Richard B. Rothman","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Richard B. Rothman","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5072534293","display_name":"Linda C. Band","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Linda Band","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"middle","author":{"id":"https://openalex.org/A5110723140","display_name":"Patricia C. Contreras","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Patricia C. Contreras","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]},{"author_position":"last","author":{"id":"https://openalex.org/A5063605002","display_name":"Nancy M. Gray","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Nancy M. Gray","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":2,"corresponding_author_ids":[],"corresponding_institution_ids":[],"apc_list":{"value":4500,"currency":"USD","value_usd":4500},"apc_paid":null,"fwci":2.2807,"has_fulltext":false,"cited_by_count":35,"citation_normalized_percentile":{"value":0.8844022,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":{"min":89,"max":95},"biblio":{"volume":"33","issue":"11","first_page":"3100","last_page":"3110"},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T13047","display_name":"Pharmacological Receptor Mechanisms and Effects","score":0.9994999766349792,"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"}},"topics":[{"id":"https://openalex.org/T13047","display_name":"Pharmacological Receptor Mechanisms and Effects","score":0.9994999766349792,"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"}},{"id":"https://openalex.org/T11178","display_name":"Receptor Mechanisms and Signaling","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"}},{"id":"https://openalex.org/T10814","display_name":"Neuropeptides and Animal Physiology","score":0.0,"subfield":{"id":"https://openalex.org/subfields/2804","display_name":"Cellular and Molecular Neuroscience"},"field":{"id":"https://openalex.org/fields/28","display_name":"Neuroscience"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/sigma-receptor-ligands","display_name":"sigma receptor ligands","score":0.890999972820282},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.9259999990463257},{"id":"https://openalex.org/keywords/kappa-opioid-receptor","display_name":"kappa opioid receptor","score":0.7480000257492065},{"id":"https://openalex.org/keywords/dopamine-d2-receptor","display_name":"dopamine D2 receptor","score":0.9850000143051147},{"id":"https://openalex.org/keywords/phencyclidine-receptor","display_name":"phencyclidine receptor","score":0.8539999723434448},{"id":"https://openalex.org/keywords/guinea-pig-brain","display_name":"guinea pig brain","score":0.6489999890327454},{"id":"https://openalex.org/keywords/receptor-binding-affinity","display_name":"receptor binding affinity","score":0.4830000102519989},{"id":"https://openalex.org/keywords/stereoisomers","display_name":"stereoisomers","score":0.5239999890327454}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.8068817853927612},{"id":"https://openalex.org/C2777346864","wikidata":"https://www.wikidata.org/wiki/Q1147539","display_name":"Cyclohexylamine","level":2,"score":0.788840651512146},{"id":"https://openalex.org/C2777052854","wikidata":"https://www.wikidata.org/wiki/Q7512419","display_name":"Sigma receptor","level":3,"score":0.7106218338012695},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.6662094593048096},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.565958559513092},{"id":"https://openalex.org/C2776730177","wikidata":"https://www.wikidata.org/wiki/Q421721","display_name":"Acetamide","level":2,"score":0.548244833946228},{"id":"https://openalex.org/C2781462491","wikidata":"https://www.wikidata.org/wiki/Q410234","display_name":"Piperidine","level":2,"score":0.49802637100219727},{"id":"https://openalex.org/C2778851735","wikidata":"https://www.wikidata.org/wiki/Q407324","display_name":"Phencyclidine","level":4,"score":0.444208025932312},{"id":"https://openalex.org/C67018056","wikidata":"https://www.wikidata.org/wiki/Q414896","display_name":"NMDA receptor","level":3,"score":0.1403314173221588},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.12845152616500854},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.07481977343559265}],"mesh":[{"descriptor_ui":"D000818","descriptor_name":"Animals","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001575","descriptor_name":"Benzomorphans","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D001667","descriptor_name":"Binding, Competitive","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D001921","descriptor_name":"Brain","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D002621","descriptor_name":"Chemistry","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D003510","descriptor_name":"Cyclohexanes","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D003510","descriptor_name":"Cyclohexanes","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D003510","descriptor_name":"Cyclohexanes","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D006168","descriptor_name":"Guinea Pigs","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D011758","descriptor_name":"Pyrroles","qualifier_ui":"Q000138","qualifier_name":"chemical synthesis","is_major_topic":true},{"descriptor_ui":"D011758","descriptor_name":"Pyrroles","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011758","descriptor_name":"Pyrroles","qualifier_ui":"Q000737","qualifier_name":"chemistry","is_major_topic":false},{"descriptor_ui":"D011759","descriptor_name":"Pyrrolidines","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011954","descriptor_name":"Receptors, Dopamine","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D011957","descriptor_name":"Receptors, Opioid","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":true},{"descriptor_ui":"D013237","descriptor_name":"Stereoisomerism","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":"D015394","descriptor_name":"Molecular Structure","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017448","descriptor_name":"Receptors, Dopamine D2","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017473","descriptor_name":"Receptors, Opioid, kappa","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017478","descriptor_name":"Receptors, Phencyclidine","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017480","descriptor_name":"Receptors, sigma","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D017981","descriptor_name":"Receptors, Neurotransmitter","qualifier_ui":"Q000378","qualifier_name":"metabolism","is_major_topic":false},{"descriptor_ui":"D044482","descriptor_name":"Benzeneacetamides","qualifier_ui":null,"qualifier_name":null,"is_major_topic":true},{"descriptor_ui":"D051381","descriptor_name":"Rats","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false},{"descriptor_ui":"D055598","descriptor_name":"Chemical Phenomena","qualifier_ui":null,"qualifier_name":null,"is_major_topic":false}],"locations_count":2,"locations":[{"id":"doi:10.1021/jm00173a030","doi":"https://doi.org/10.1021/jm00173a030","is_oa":false,"landing_page_url":"https://doi.org/10.1021/jm00173a030","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:2172538","doi":null,"is_oa":false,"landing_page_url":"https://pubmed.ncbi.nlm.nih.gov/2172538","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":"Comparative Study"}],"best_oa_location":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.46810001134872437}],"study_designs":[],"awards":[],"funders":[],"has_content":{"grobid_xml":false,"pdf":false},"content_urls":null,"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W2062664011","https://openalex.org/W1985396940","https://openalex.org/W2003715023","https://openalex.org/W2076041228","https://openalex.org/W1999149222","https://openalex.org/W2056693874","https://openalex.org/W2137908724","https://openalex.org/W2243198080","https://openalex.org/W2078712122","https://openalex.org/W2953094740"],"abstract_inverted_index":{"Certain":[0],"benzeneacetamides":[1],"[(-)-":[2],"and":[3,40,58,66,70,86,120,176,182],"(+)-cis-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)":[4],"cyclohexyl]benzeneacetamide]":[5],"were":[6,38,44,48],"recently":[7],"reported":[8,55],"to":[9,17,33,178],"be":[10,26],"potent":[11,85],"sigma":[12,23,62,88,136,163,193],"receptor":[13,24,74,89,194],"ligands.":[14,90],"In":[15],"order":[16],"determine":[18],"whether":[19],"efficacy":[20],"for":[21,149,159,174,180],"the":[22,34,53,160],"could":[25],"improved,":[27],"a":[28,81],"series":[29],"of":[30,61,83,140,162],"compounds":[31,47,145,167,186],"related":[32],"benzeneacetamides,":[35],"N-substituted":[36],"cis-2-(1-pyrrolidinyl)-N-methylcyclohexylamines,":[37],"synthesized":[39,49],"their":[41],"structure-activity":[42],"requirements":[43],"determined.":[45],"The":[46],"by":[50,138],"starting":[51],"with":[52],"previously":[54],"(+/-)-,":[56],"1S,2R-(+)-,":[57],"1R,2S-(-)-cis-2-(1-pyrrolidinyl)-N-methylcyclohexylamines.":[59],"Analysis":[60],"([3H](+)-3-PPP),":[63],"kappa":[64],"([3H]bremazocine":[65],"[3H]U69,593),":[67],"dopamine-d2":[68],"([3H](-)-sulpiride),":[69],"phencyclidine":[71],"(PCP)":[72],"([3H]TCP)":[73],"binding":[75],"in":[76],"guinea":[77],"pig":[78],"brain":[79],"revealed":[80],"number":[82],"highly":[84],"selective":[87],"Notably,":[91],"1S,2R-cis-(-)-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-(2-naphthyl)":[92],"acetamide":[93],"[(-)-29]":[94],"(Ki":[95,104,114,125],"=":[96,105,115,126],"8.66":[97],"+/-":[98,107,117,128],"0.35":[99],"nM),":[100,109,119],"(+/-)-cis-2-amino-4,5-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]":[101],"benzeneacetamide":[102],"[(+/-)-17]":[103],"11":[106],"3":[108,129],"1S,2R-(-)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl":[110],")":[111,122],"cyclohexylamine":[112],"[(-)-44]":[113],"1.3":[116],"0.3":[118],"1R,2S-(+)-cis-N-methyl-N-[2-(3,4-dichlorophenyl)ethyl]-2-(1-pyrrolidinyl":[121],"cyclohexylamine.":[123],"[(+)-44]":[124],"6":[127],"nM)":[130],"exhibited":[131,169],"very":[132],"high":[133],"affinity":[134,148],"at":[135],"receptors,":[137,154],"displacement":[139],"[3H]-(+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine":[141],"[(":[142],"3H]-(+)-3-PPP).":[143],"These":[144],"showed":[146,187],"insignificant":[147],"kappa,":[150],"dopamine,":[151],"or":[152],"PCP":[153],"making":[155],"them":[156],"valuable":[157],"tools":[158],"study":[161],"receptors.":[164],"Furthermore,":[165],"these":[166],"also":[168],"enantioselectivity":[170],"ranging":[171],"from":[172],"5-fold":[173],"(+)-":[175,181],"(-)-44":[177],"160-fold":[179],"(-)-29.":[183],"Several":[184],"other":[185],"equivalent":[188],"selectivity":[189],"but":[190],"displayed":[191],"lower":[192],"affinity.":[195]},"counts_by_year":[{"year":2021,"cited_by_count":2},{"year":2017,"cited_by_count":1},{"year":2012,"cited_by_count":1}],"updated_date":"2026-10-31T12:09:11.096373","created_date":"2016-06-24T00:00:00"}
