{"id":"https://openalex.org/W778019108","doi":null,"title":"Design, synthesis, and pharmacological evaluation of three series of lobelane analogs as inhibitors of the vesicular monoamine transporter (VMAT2)","display_name":"Design, synthesis, and pharmacological evaluation of three series of lobelane analogs as inhibitors of the vesicular monoamine transporter (VMAT2)","publication_year":2015,"publication_date":"2015-01-01","ids":{"openalex":"https://openalex.org/W778019108","mag":"778019108"},"language":"en","primary_location":{"id":"pmh:oai:uknowledge.uky.edu:pharmacy_etds-1049","doi":null,"is_oa":true,"landing_page_url":"https://uknowledge.uky.edu/pharmacy_etds/46","pdf_url":"https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1049&context=pharmacy_etds","source":{"id":"https://openalex.org/S4306402623","display_name":"UKnowledge (University of Kentucky)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I143302722","host_organization_name":"University of Kentucky","host_organization_lineage":["https://openalex.org/I143302722"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Theses and Dissertations--Pharmacy","raw_type":"text"},"volume":null,"type":"article","is_traditional":true,"indexed_in":[],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1049&context=pharmacy_etds","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5057941368","display_name":"John P. Culver","orcid":null,"observed_orcids":[]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"John P. Culver","raw_affiliation_strings":[],"raw_orcid":null,"affiliations":[]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5057941368"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":0.0,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":{"value":0.00704367,"is_in_top_1_percent":false,"is_in_top_10_percent":false},"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T12649","display_name":"Alkaloids: synthesis and pharmacology","score":0.3440000116825104,"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"}},"topics":[{"id":"https://openalex.org/T12649","display_name":"Alkaloids: synthesis and pharmacology","score":0.3440000116825104,"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/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.24609999358654022,"subfield":{"id":"https://openalex.org/subfields/1605","display_name":"Organic Chemistry"},"field":{"id":"https://openalex.org/fields/16","display_name":"Chemistry"},"domain":{"id":"https://openalex.org/domains/3","display_name":"Physical Sciences"}},{"id":"https://openalex.org/T10056","display_name":"Neurotransmitter Receptor Influence on Behavior","score":0.07339999824762344,"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/vmat2","display_name":"vesicular monoamine transporter 2","score":0.871999979019165},{"id":"https://openalex.org/keywords/vmat2-inhibitors","display_name":"VMAT2 inhibitors","score":0.9340000152587891},{"id":"https://openalex.org/keywords/methamphetamine-abuse","display_name":"methamphetamine abuse","score":0.8360000252723694},{"id":"https://openalex.org/keywords/dopamine-uptake","display_name":"dopamine uptake","score":0.5630000233650208},{"id":"https://openalex.org/keywords/lobeline","display_name":"lobeline","score":0.6959999799728394},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.796999990940094},{"id":"https://openalex.org/keywords/pharmacophore-model","display_name":"pharmacophore model","score":0.8629999756813049},{"id":"https://openalex.org/keywords/rational-drug-design","display_name":"rational drug design","score":0.7450000047683716},{"id":"https://openalex.org/keywords/organic-synthesis","display_name":"organic synthesis","score":0.4819999933242798}],"concepts":[{"id":"https://openalex.org/C187714386","wikidata":"https://www.wikidata.org/wiki/Q420225","display_name":"Monoamine neurotransmitter","level":4,"score":0.761267900466919},{"id":"https://openalex.org/C2778406628","wikidata":"https://www.wikidata.org/wiki/Q2521094","display_name":"Vesicular monoamine transporter 2","level":5,"score":0.7565891146659851},{"id":"https://openalex.org/C2776291748","wikidata":"https://www.wikidata.org/wiki/Q4105920","display_name":"Vesicular monoamine transporter","level":5,"score":0.7434831857681274},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.7258792519569397},{"id":"https://openalex.org/C98274493","wikidata":"https://www.wikidata.org/wiki/Q128406","display_name":"Pharmacology","level":1,"score":0.5488765835762024},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.5328624248504639},{"id":"https://openalex.org/C2780114369","wikidata":"https://www.wikidata.org/wiki/Q6823535","display_name":"Meth-","level":5,"score":0.5129191875457764},{"id":"https://openalex.org/C2780376393","wikidata":"https://www.wikidata.org/wiki/Q191924","display_name":"Methamphetamine","level":2,"score":0.4731736481189728},{"id":"https://openalex.org/C149011108","wikidata":"https://www.wikidata.org/wiki/Q652985","display_name":"Transporter","level":3,"score":0.46403929591178894},{"id":"https://openalex.org/C513476851","wikidata":"https://www.wikidata.org/wiki/Q170304","display_name":"Dopamine","level":2,"score":0.4501384496688843},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.34289979934692383},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.17145508527755737},{"id":"https://openalex.org/C2775864247","wikidata":"https://www.wikidata.org/wiki/Q167934","display_name":"Serotonin","level":3,"score":0.16106504201889038},{"id":"https://openalex.org/C170493617","wikidata":"https://www.wikidata.org/wiki/Q208467","display_name":"Receptor","level":2,"score":0.1534958779811859},{"id":"https://openalex.org/C169760540","wikidata":"https://www.wikidata.org/wiki/Q207011","display_name":"Neuroscience","level":1,"score":0.10110968351364136},{"id":"https://openalex.org/C178790620","wikidata":"https://www.wikidata.org/wiki/Q11351","display_name":"Organic chemistry","level":1,"score":0.07074844837188721},{"id":"https://openalex.org/C166940927","wikidata":"https://www.wikidata.org/wiki/Q178827","display_name":"Monomer","level":3,"score":0.0},{"id":"https://openalex.org/C2779989194","wikidata":"https://www.wikidata.org/wiki/Q343016","display_name":"Acrylate","level":4,"score":0.0},{"id":"https://openalex.org/C521977710","wikidata":"https://www.wikidata.org/wiki/Q81163","display_name":"Polymer","level":2,"score":0.0},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":3,"locations":[{"id":"pmh:oai:uknowledge.uky.edu:pharmacy_etds-1049","doi":null,"is_oa":true,"landing_page_url":"https://uknowledge.uky.edu/pharmacy_etds/46","pdf_url":"https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1049&context=pharmacy_etds","source":{"id":"https://openalex.org/S4306402623","display_name":"UKnowledge (University of Kentucky)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I143302722","host_organization_name":"University of Kentucky","host_organization_lineage":["https://openalex.org/I143302722"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Theses and Dissertations--Pharmacy","raw_type":"text"},{"id":"pmh:oai:CiteSeerX.psu:10.1.1.1005.8593","doi":null,"is_oa":false,"landing_page_url":"http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.1005.8593","pdf_url":null,"source":null,"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"http://uknowledge.uky.edu/cgi/viewcontent.cgi?article%3D1049%26context%3Dpharmacy_etds","raw_type":"text"},{"id":"mag:778019108","doi":null,"is_oa":false,"landing_page_url":"https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1049&context=pharmacy_etds","pdf_url":null,"source":null,"license":null,"license_id":null,"version":null,"is_accepted":false,"is_published":false,"raw_source_name":null,"raw_type":null}],"best_oa_location":{"id":"pmh:oai:uknowledge.uky.edu:pharmacy_etds-1049","doi":null,"is_oa":true,"landing_page_url":"https://uknowledge.uky.edu/pharmacy_etds/46","pdf_url":"https://uknowledge.uky.edu/cgi/viewcontent.cgi?article=1049&context=pharmacy_etds","source":{"id":"https://openalex.org/S4306402623","display_name":"UKnowledge (University of Kentucky)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I143302722","host_organization_name":"University of Kentucky","host_organization_lineage":["https://openalex.org/I143302722"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"Theses and Dissertations--Pharmacy","raw_type":"text"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.8048999905586243}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W778019108.pdf","grobid_xml":"https://content.openalex.org/works/W778019108.grobid-xml"},"referenced_works_count":167,"referenced_works":["https://openalex.org/W71626638","https://openalex.org/W149738019","https://openalex.org/W164353120","https://openalex.org/W205578041","https://openalex.org/W587316722","https://openalex.org/W1496507967","https://openalex.org/W1552189630","https://openalex.org/W1596017072","https://openalex.org/W1598364670","https://openalex.org/W1761725356","https://openalex.org/W1879399529","https://openalex.org/W1921401097","https://openalex.org/W1923591030","https://openalex.org/W1933665998","https://openalex.org/W1959337655","https://openalex.org/W1964227107","https://openalex.org/W1966835560","https://openalex.org/W1968578851","https://openalex.org/W1971434876","https://openalex.org/W1973680024","https://openalex.org/W1974211383","https://openalex.org/W1974587963","https://openalex.org/W1977049293","https://openalex.org/W1978323537","https://openalex.org/W1978450909","https://openalex.org/W1981283169","https://openalex.org/W1982038512","https://openalex.org/W1984186801","https://openalex.org/W1990299071","https://openalex.org/W1990793586","https://openalex.org/W1991141166","https://openalex.org/W1995089537","https://openalex.org/W1995540657","https://openalex.org/W1996691551","https://openalex.org/W1996911010","https://openalex.org/W1999406499","https://openalex.org/W1999434743","https://openalex.org/W2002579084","https://openalex.org/W2003598035","https://openalex.org/W2007509215","https://openalex.org/W2008802395","https://openalex.org/W2009660859","https://openalex.org/W2011854027","https://openalex.org/W2014488168","https://openalex.org/W2018159164","https://openalex.org/W2019194654","https://openalex.org/W2019307609","https://openalex.org/W2019977359","https://openalex.org/W2021551394","https://openalex.org/W2021573246","https://openalex.org/W2023522042","https://openalex.org/W2023590101","https://openalex.org/W2024419912","https://openalex.org/W2026261422","https://openalex.org/W2027314713","https://openalex.org/W2027376809","https://openalex.org/W2028372004","https://openalex.org/W2028980876","https://openalex.org/W2030424849","https://openalex.org/W2030969967","https://openalex.org/W2031305070","https://openalex.org/W2032816843","https://openalex.org/W2033158324","https://openalex.org/W2033655776","https://openalex.org/W2034781595","https://openalex.org/W2036061929","https://openalex.org/W2036408094","https://openalex.org/W2038071695","https://openalex.org/W2038763233","https://openalex.org/W2039262224","https://openalex.org/W2040110015","https://openalex.org/W2041936284","https://openalex.org/W2043018270","https://openalex.org/W2049098433","https://openalex.org/W2050162594","https://openalex.org/W2052122668","https://openalex.org/W2054576645","https://openalex.org/W2059484499","https://openalex.org/W2060279833","https://openalex.org/W2061199300","https://openalex.org/W2061409026","https://openalex.org/W2061832190","https://openalex.org/W2064225780","https://openalex.org/W2064431700","https://openalex.org/W2065376500","https://openalex.org/W2066998306","https://openalex.org/W2070802389","https://openalex.org/W2073855211","https://openalex.org/W2074163153","https://openalex.org/W2074510414","https://openalex.org/W2074631079","https://openalex.org/W2074726560","https://openalex.org/W2075347406","https://openalex.org/W2075732363","https://openalex.org/W2077948870","https://openalex.org/W2077955240","https://openalex.org/W2080631930","https://openalex.org/W2080720254","https://openalex.org/W2082768478","https://openalex.org/W2084276613","https://openalex.org/W2084708128","https://openalex.org/W2085674390","https://openalex.org/W2086477999","https://openalex.org/W2087093318","https://openalex.org/W2087288531","https://openalex.org/W2088040462","https://openalex.org/W2088630967","https://openalex.org/W2089962752","https://openalex.org/W2091817782","https://openalex.org/W2091906332","https://openalex.org/W2092446825","https://openalex.org/W2092810393","https://openalex.org/W2094901175","https://openalex.org/W2095867336","https://openalex.org/W2098553992","https://openalex.org/W2098837867","https://openalex.org/W2100509512","https://openalex.org/W2103129019","https://openalex.org/W2103660407","https://openalex.org/W2103827356","https://openalex.org/W2104506785","https://openalex.org/W2104842452","https://openalex.org/W2106287416","https://openalex.org/W2106870650","https://openalex.org/W2108264967","https://openalex.org/W2108687452","https://openalex.org/W2111760499","https://openalex.org/W2114144700","https://openalex.org/W2120077675","https://openalex.org/W2120615639","https://openalex.org/W2122592499","https://openalex.org/W2124676204","https://openalex.org/W2127247379","https://openalex.org/W2127622764","https://openalex.org/W2128432842","https://openalex.org/W2131622291","https://openalex.org/W2134898475","https://openalex.org/W2138563618","https://openalex.org/W2142154804","https://openalex.org/W2142352958","https://openalex.org/W2143308851","https://openalex.org/W2144176813","https://openalex.org/W2145434123","https://openalex.org/W2152226751","https://openalex.org/W2155000996","https://openalex.org/W2158308863","https://openalex.org/W2159271171","https://openalex.org/W2162992703","https://openalex.org/W2163320407","https://openalex.org/W2195565602","https://openalex.org/W2207875738","https://openalex.org/W2255883331","https://openalex.org/W2260705831","https://openalex.org/W2271897004","https://openalex.org/W2299861533","https://openalex.org/W2346695454","https://openalex.org/W2370648048","https://openalex.org/W2397109448","https://openalex.org/W2417384392","https://openalex.org/W2418425221","https://openalex.org/W2419650429","https://openalex.org/W2491941502","https://openalex.org/W2500163389","https://openalex.org/W2950481339","https://openalex.org/W2952346845","https://openalex.org/W2953254217","https://openalex.org/W2953391360"],"related_works":["https://openalex.org/W2155000996","https://openalex.org/W1973680024","https://openalex.org/W1573952878","https://openalex.org/W2153923176","https://openalex.org/W1498167757","https://openalex.org/W2028818514","https://openalex.org/W568328589","https://openalex.org/W2095867336","https://openalex.org/W1978450909","https://openalex.org/W2011883310"],"abstract_inverted_index":{"Methamphetamine":[0],"(METH)":[1],"abuse":[2],"is":[3,19,100],"a":[4,81,101,106,136,158,172],"serious":[5],"problem":[6],"in":[7,24,90,110,157,171],"the":[8,22,36,43,60,69,85,95,189,231,236],"United":[9],"States":[10],"and":[11,35,62,121,129,150,204,226],"worldwide.":[12],"The":[13,48,65,208],"reward":[14,49],"experienced":[15],"by":[16,30,51],"METH":[17,34,54],"users":[18,52],"due":[20],"to":[21,56,78,93,117,119,134,252],"increase":[23],"extracellular":[25],"dopamine":[26],"(DA)":[27],"concentrations":[28],"caused":[29],"an":[31,91],"interaction":[32],"between":[33],"DA":[37,174],"transporter":[38],"(DAT)":[39],"as":[40,42,166,168,184,186],"well":[41,167,185],"Vesicular":[44,86],"Monoamine":[45,87],"Transporter-2":[46,88],"(VMAT2).":[47],"felt":[50],"of":[53,59,71,75,97,104,138,141,214,238],"leads":[55],"further":[57],"use":[58],"drug":[61,126],"subsequent":[63],"abuse.":[64],"current":[66],"project":[67],"examined":[68],"ability":[70],"three":[72,139],"novel":[73],"series":[74,140],"lobelane":[76,142],"analogs":[77],"interact":[79],"with":[80],"binding":[82,164,191],"site":[83,192],"on":[84,193],"(VMAT2)":[89],"attempt":[92],"inhibit":[94,122],"effects":[96],"METH.":[98],"Lobelane":[99],"defunctionalized":[102],"analog":[103],"Lobeline,":[105],"natural":[107],"product":[108],"found":[109],"Lobelia":[111],"inflata":[112],"which":[113,181],"has":[114],"been":[115],"shown":[116],"bind":[118],"VMAT2":[120,194],"its":[123],"function.":[124],"Rational":[125],"design":[127],"methodology":[128],"organic":[130],"synthesis":[131],"was":[132],"used":[133],"generate":[135],"library":[137,237],"analogs.":[143],"In":[144],"total,":[145],"107":[146],"compounds":[147,178,211],"were":[148,153,179,250],"synthesized":[149],"examined.":[151],"Compounds":[152],"assayed":[154],"for":[155,169,188],"affinity":[156,183],"high-throughput":[159],"[3H]":[160,173],"dihydrotetrabenazine":[161],"(DTBZ)":[162],"radioligand":[163],"screen":[165],"function":[170],"uptake":[175,216],"assay.":[176],"Several":[177],"identified":[180],"possess":[182],"selectivity":[187],"DTBZ":[190],"[JPC-077":[195,217],"(Ki=0.19":[196,202,206],"\u03bcM),":[197,200,203],"JPC-094":[198,220],"(Ki=0.15":[199],"JPC-096":[201,223],"JPC-106":[205,227],"\u03bcM)].":[207],"same":[209],"four":[210],"exhibited":[212],"inhibition":[213],"[3H]DA":[215],"(Ki=9.3":[218],"nM),":[219,222,225],"(Ki=13":[221],"(Ki=20":[224],"(Ki=83":[228],"nM)].":[229],"With":[230],"assay":[232],"data":[233],"generated":[234],"from":[235],"compounds,":[239],"several":[240],"structure":[241],"activity":[242],"relationship":[243],"(SAR)":[244],"based":[245,247],"ligand":[246,255],"pharmacophore":[248],"models":[249],"developed":[251],"guide":[253],"future":[254],"design.":[256]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}