{"id":"https://openalex.org/W853456509","doi":null,"title":"Design and synthesis of selective inhibitors of poly(ADP-ribose)polymerase-2","display_name":"Design and synthesis of selective inhibitors of poly(ADP-ribose)polymerase-2","publication_year":2010,"publication_date":"2010-01-01","ids":{"openalex":"https://openalex.org/W853456509","mag":"853456509"},"language":"en","primary_location":{"id":"pmh:oai:opus.bath.ac.uk:48035","doi":null,"is_oa":false,"landing_page_url":"http://opus.bath.ac.uk/48035/1/UnivBath_PhD_2010_P_Sunderland.pdf","pdf_url":"http://opus.bath.ac.uk/48035/1/UnivBath_PhD_2010_P_Sunderland.pdf","source":{"id":"https://openalex.org/S4306401631","display_name":"The University of Bath Online Publications Store (The University of Bath)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I51601045","host_organization_name":"University of Bath","host_organization_lineage":["https://openalex.org/I51601045"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Thesis"},"volume":null,"type":"dissertation","is_traditional":true,"indexed_in":[],"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/A5074595713","display_name":"Peter Sunderland","orcid":"https://orcid.org/0009-0001-5020-8251","observed_orcids":["https://orcid.org/0009-0001-5020-8251"]},"institutions":[],"countries":[],"is_corresponding":true,"raw_author_name":"Peter T. Sunderland","raw_affiliation_strings":["Department of Pharmacy & Pharmacology"],"raw_orcid":"https://orcid.org/0009-0001-5020-8251","affiliations":[{"raw_affiliation_string":"Department of Pharmacy & Pharmacology","institution_ids":[]}]}],"institutions":[],"countries_distinct_count":0,"institutions_distinct_count":0,"corresponding_author_ids":["https://openalex.org/A5074595713"],"corresponding_institution_ids":[],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"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/T11914","display_name":"PARP inhibition in cancer therapy","score":0.9365000128746033,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T11914","display_name":"PARP inhibition in cancer therapy","score":0.9365000128746033,"subfield":{"id":"https://openalex.org/subfields/2730","display_name":"Oncology"},"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/T10274","display_name":"Heterocyclic Compound Synthesis and Bioactivity","score":0.019300000742077827,"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/T13971","display_name":"Isoquinoline Alkaloid Synthesis","score":0.005100000184029341,"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"}}],"keywords":[{"id":"https://openalex.org/keywords/isoform-selective-inhibitors","display_name":"isoform-selective inhibitors","score":0.9269999861717224},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.5540000200271606}],"concepts":[{"id":"https://openalex.org/C182979987","wikidata":"https://www.wikidata.org/wiki/Q3907241","display_name":"Poly ADP ribose polymerase","level":4,"score":0.8616163730621338},{"id":"https://openalex.org/C82381507","wikidata":"https://www.wikidata.org/wiki/Q416878","display_name":"Polymerase","level":3,"score":0.5701810717582703},{"id":"https://openalex.org/C2779461342","wikidata":"https://www.wikidata.org/wiki/Q59817493","display_name":"Ribose","level":3,"score":0.5002059936523438},{"id":"https://openalex.org/C134935766","wikidata":"https://www.wikidata.org/wiki/Q210538","display_name":"DNA repair","level":3,"score":0.49886250495910645},{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.4980006217956543},{"id":"https://openalex.org/C181199279","wikidata":"https://www.wikidata.org/wiki/Q8047","display_name":"Enzyme","level":2,"score":0.47125935554504395},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.46497464179992676},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.41523343324661255},{"id":"https://openalex.org/C552990157","wikidata":"https://www.wikidata.org/wiki/Q7430","display_name":"DNA","level":2,"score":0.3820685148239136},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.33587121963500977}],"mesh":[],"locations_count":3,"locations":[{"id":"pmh:oai:opus.bath.ac.uk:48035","doi":null,"is_oa":false,"landing_page_url":"http://opus.bath.ac.uk/48035/1/UnivBath_PhD_2010_P_Sunderland.pdf","pdf_url":"http://opus.bath.ac.uk/48035/1/UnivBath_PhD_2010_P_Sunderland.pdf","source":{"id":"https://openalex.org/S4306401631","display_name":"The University of Bath Online Publications Store (The University of Bath)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I51601045","host_organization_name":"University of Bath","host_organization_lineage":["https://openalex.org/I51601045"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"Thesis"},{"id":"pmh:hdl:10068/977287","doi":null,"is_oa":false,"landing_page_url":"http://hdl.handle.net/10068/977287","pdf_url":null,"source":{"id":"https://openalex.org/S4377196900","display_name":"OpenGrey (Institut de l'Information Scientifique et Technique)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I1295345811","host_organization_name":"Institut de l'Information Scientifique et Technique","host_organization_lineage":["https://openalex.org/I1295345811"],"host_organization_lineage_names":[],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"","raw_type":"U - Thesis"},{"id":"mag:853456509","doi":null,"is_oa":false,"landing_page_url":"http://opus.bath.ac.uk/48035/1/UnivBath_PhD_2010_P_Sunderland.pdf","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":null,"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being","score":0.4000000059604645}],"study_designs":[],"awards":[],"funders":[],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":158,"referenced_works":["https://openalex.org/W159690873","https://openalex.org/W270470139","https://openalex.org/W1494693574","https://openalex.org/W1503306485","https://openalex.org/W1513018272","https://openalex.org/W1522147759","https://openalex.org/W1532907366","https://openalex.org/W1533458170","https://openalex.org/W1541877559","https://openalex.org/W1548727679","https://openalex.org/W1584549675","https://openalex.org/W1609541309","https://openalex.org/W1848063234","https://openalex.org/W1966363887","https://openalex.org/W1966928113","https://openalex.org/W1966934669","https://openalex.org/W1968625783","https://openalex.org/W1973173167","https://openalex.org/W1973269473","https://openalex.org/W1975255909","https://openalex.org/W1978367221","https://openalex.org/W1978848753","https://openalex.org/W1979181763","https://openalex.org/W1980200829","https://openalex.org/W1980511120","https://openalex.org/W1981510143","https://openalex.org/W1982734887","https://openalex.org/W1983609323","https://openalex.org/W1985768828","https://openalex.org/W1986269716","https://openalex.org/W1987031739","https://openalex.org/W1992332625","https://openalex.org/W1992994583","https://openalex.org/W1993972255","https://openalex.org/W1994011134","https://openalex.org/W1998596873","https://openalex.org/W2001912872","https://openalex.org/W2002638727","https://openalex.org/W2005458257","https://openalex.org/W2010348785","https://openalex.org/W2013605216","https://openalex.org/W2014150894","https://openalex.org/W2014599726","https://openalex.org/W2016824159","https://openalex.org/W2018020379","https://openalex.org/W2018329608","https://openalex.org/W2019181874","https://openalex.org/W2025550674","https://openalex.org/W2026405645","https://openalex.org/W2028392042","https://openalex.org/W2031623053","https://openalex.org/W2031832448","https://openalex.org/W2032407757","https://openalex.org/W2033079929","https://openalex.org/W2033761616","https://openalex.org/W2034753237","https://openalex.org/W2035611840","https://openalex.org/W2037316481","https://openalex.org/W2039199479","https://openalex.org/W2039200583","https://openalex.org/W2039611537","https://openalex.org/W2040206596","https://openalex.org/W2040789304","https://openalex.org/W2041424415","https://openalex.org/W2042057833","https://openalex.org/W2043195694","https://openalex.org/W2044846885","https://openalex.org/W2045751930","https://openalex.org/W2046572356","https://openalex.org/W2047807761","https://openalex.org/W2049375001","https://openalex.org/W2050057632","https://openalex.org/W2055580680","https://openalex.org/W2057706543","https://openalex.org/W2058696051","https://openalex.org/W2060321052","https://openalex.org/W2060654492","https://openalex.org/W2062747680","https://openalex.org/W2062814676","https://openalex.org/W2064830796","https://openalex.org/W2069049558","https://openalex.org/W2069910776","https://openalex.org/W2072325915","https://openalex.org/W2072528578","https://openalex.org/W2072609569","https://openalex.org/W2072716533","https://openalex.org/W2074823657","https://openalex.org/W2075875680","https://openalex.org/W2079054585","https://openalex.org/W2080476839","https://openalex.org/W2083424511","https://openalex.org/W2089407891","https://openalex.org/W2090457646","https://openalex.org/W2090574266","https://openalex.org/W2091035559","https://openalex.org/W2091041535","https://openalex.org/W2092672926","https://openalex.org/W2093306117","https://openalex.org/W2093814798","https://openalex.org/W2097642827","https://openalex.org/W2099904057","https://openalex.org/W2101117526","https://openalex.org/W2101904590","https://openalex.org/W2105271014","https://openalex.org/W2106390123","https://openalex.org/W2108051742","https://openalex.org/W2109081379","https://openalex.org/W2112671059","https://openalex.org/W2114344808","https://openalex.org/W2116508133","https://openalex.org/W2116804853","https://openalex.org/W2119048840","https://openalex.org/W2120396502","https://openalex.org/W2121272379","https://openalex.org/W2122386753","https://openalex.org/W2125343208","https://openalex.org/W2125528957","https://openalex.org/W2126866610","https://openalex.org/W2128016549","https://openalex.org/W2128211373","https://openalex.org/W2132324298","https://openalex.org/W2133771754","https://openalex.org/W2134316981","https://openalex.org/W2139251958","https://openalex.org/W2144711308","https://openalex.org/W2145577632","https://openalex.org/W2146830757","https://openalex.org/W2148944173","https://openalex.org/W2150805674","https://openalex.org/W2155169828","https://openalex.org/W2156442575","https://openalex.org/W2158849923","https://openalex.org/W2160073632","https://openalex.org/W2165096527","https://openalex.org/W2165432409","https://openalex.org/W2165970909","https://openalex.org/W2168169655","https://openalex.org/W2168209323","https://openalex.org/W2168496620","https://openalex.org/W2169274959","https://openalex.org/W2176655192","https://openalex.org/W2270250885","https://openalex.org/W2320533490","https://openalex.org/W2325021350","https://openalex.org/W2325814368","https://openalex.org/W2339515695","https://openalex.org/W2411064654","https://openalex.org/W2432429035","https://openalex.org/W2465485650","https://openalex.org/W2949770808","https://openalex.org/W2950998879","https://openalex.org/W2951088649","https://openalex.org/W2951804023","https://openalex.org/W2952136057","https://openalex.org/W2952422013","https://openalex.org/W2952634359","https://openalex.org/W2952763183","https://openalex.org/W2952954173"],"related_works":["https://openalex.org/W2088068651","https://openalex.org/W2058696051","https://openalex.org/W2080367627","https://openalex.org/W2903137310","https://openalex.org/W7217605825","https://openalex.org/W2078260055","https://openalex.org/W2951998010","https://openalex.org/W3109253207","https://openalex.org/W1965675001","https://openalex.org/W2073537302"],"abstract_inverted_index":{"The":[0,19,96,285,303,326,365],"poly(ADP-ribose)":[1],"polymerases":[2],"(PARPs)":[3],"are":[4],"a":[5,123,233,254],"family":[6,55],"of":[7,13,23,48,52,63,83,129,139,150,159,168,183,194,215,275,287,294,350,381,407],"enzymes":[8],"that":[9],"catalyse":[10],"the":[11,38,46,49,53,64,68,80,116,137,140,146,166,169,223,248,272,276,309,323,348,356,416,429],"transfer":[12],"ADP-ribose":[14],"polymers":[15],"onto":[16],"acceptor":[17],"proteins.":[18],"biology":[20],"and":[21,93,112,148,153,227,296,316,422],"biochemistry":[22],"PARP-1":[24,239],"has":[25,85,98,425],"been":[26,86,99],"extensively":[27],"studied":[28],"and,":[29,70],"for":[30,42,61,126,208,236,258,377],"many":[31],"years,":[32],"this":[33,435],"was":[34,244,370,373,385,412],"thought":[35],"to":[36,77,101,131,135,247,307,313,433],"be":[37],"sole":[39],"protein":[40,97],"responsible":[41,60],"poly(ADP-ribosyl)ation":[43,65],"reactions.":[44],"However,":[45],"functions":[47,138],"remaining":[50],"members":[51],"PARP":[54,402],"remain":[56],"unclear.":[57],"PARP-2":[58,84,130,171,209,237,259],"is":[59,73,118,121,305],"1015%":[62],"reactions":[66],"in":[67,106,240,245,260,335,347,414],"cell":[69],"like":[71],"PARP-1,":[72],"activated":[74],"by":[75,88,192,219,299,354,427],"damage":[76],"DNA.":[78],"Recently,":[79],"biological":[81,155],"importance":[82],"illustrated":[87],"studies":[89],"using":[90,271,387],"knockout":[91],"mice":[92],"antisense":[94],"RNA.":[95],"shown":[100],"have":[102],"an":[103,290],"important":[104,436],"role":[105],"DNA":[107],"repair,":[108],"telomeric":[109],"integrity,":[110],"inflammation":[111],"cellular":[113],"differentiation;":[114],"but":[115,201,279,339,353],"picture":[117],"cloudy.":[119],"There":[120],"currently":[122],"major":[124],"requirement":[125],"isoform-selective":[127],"inhibitors":[128],"use":[132],"as":[133,322],"tools":[134],"study":[136],"enzyme.":[141],"This":[142,243,424],"work":[143],"focuses":[144],"upon":[145],"design":[147],"synthesis":[149,349,406],"these":[151,202,288,394],"molecules":[152,203],"their":[154],"evaluation.":[156],"Three":[157],"sets":[158],"target":[160],"compounds":[161,267,328,395],"were":[162,190,217,228,268,283,329,340,345,359,396,420],"proposed,":[163],"based":[164],"on":[165],"structure":[167],"murine":[170],"active":[172,399],"site":[173],"with":[174,186,199,222,320,337,362],"our":[175,241,261,408],"lead":[176,409],"compound":[177,251,369,410],"5-AIQ":[178,195,221,338,411],"docked.":[179],"An":[180],"initial":[181,291],"series":[182,380],"5substituted":[184],"5-AIQs":[185,384],"carboxylic":[187],"acids":[188],"tethered":[189],"prepared":[191,218,270],"alkylation":[193],"or":[196],"Heck":[197],"reaction":[198,278,293,319],"5-iodoisoquinolin-1-one":[200],"did":[204],"not":[205,341,397],"show":[206],"selectivity":[207,235,257],"over":[210,238],"PARP-1.":[211],"A":[212,379,404],"further":[213],"set":[214],"5-acylaminoisoquinolin-1-ones":[216],"treating":[220],"appropriate":[224],"acid":[225],"chloride":[226],"more":[229],"promising.":[230],"5-benzamidoisoquinolinone":[231],"displayed":[232],"9-fold":[234],"assays.":[242],"contrast":[246],"best":[249],"literature":[250],"which":[252,372,415],"had":[253],"ca.":[255,374],"3-fold":[256],"system":[262],"(reported":[263],"60-fold":[264],"selectivity).":[265],"3-substituted":[266,327],"initially":[269],"established":[273],"chemistry":[274],"Hurtley":[277],"two":[280],"new":[281,405],"routes":[282],"developed.":[284],"first":[286],"involved":[289],"Friedel-Crafts":[292],"5-nitroisocoumarin":[295],"rearrangement":[297],"followed":[298],"decarbonylation":[300],"/":[301],"decarboxylation.":[302],"second":[304],"likely":[306],"become":[308,426],"most":[310,357,366,430],"efficient":[311,431],"way":[312,432],"synthesise":[314,434],"3-aryl-5-nitroisoquinolin-1-ones":[315],"involves":[317],"Suzuki":[318],"3chloro-1-methoxyisoquinoline":[321],"key":[324],"step.":[325],"generally":[330],"highly":[331],"potent":[332],"against":[333,400],"PARP-1/2":[334],"comparison":[336],"selective.":[342],"Several":[343],"approaches":[344],"explored":[346],"4-substituted":[351,368],"isoquinolin-1-ones":[352],"far":[355,428],"successful":[358],"palladium-catalysed":[360],"couplings":[361],"protected":[363],"4-bromo-5nitroisoquinolin-1-ones.":[364],"promising":[367],"5-amino-4-(4trifluromethyl)isoquinolin-1-one":[371],"8-fold":[375],"selective":[376],"PARP-2.":[378],"3,5and":[382],"4,5-disubstituted":[383],"generated":[386],"previously":[388],"developed":[389,413],"chemistry.":[390],"Biological":[391],"evaluation":[392],"showed":[393],"significantly":[398],"either":[401],"isoform.":[403],"only":[417],"purification":[418],"steps":[419],"filtration":[421],"recrystallisation.":[423],"molecule.":[437]},"counts_by_year":[],"updated_date":"2026-11-04T10:54:05.112534","created_date":"2016-06-24T00:00:00"}