?url_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Adc&rft.relation=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F33064%2F&rft.title=SYNTHESIS+OF+THIOPHENE-CONTAINING+HETEROCYCLES+AND+THEIR+APPLICATION+AS+ANTICANCER+AGENTS&rft.creator=Salamoun%2C+Joseph+M&rft.description=Five-membered+heterocycles+represent+a+privileged+scaffold+in+drug+discovery+and+are+the+focus+of+analog+design.+The+first+chapter+presents+the+synthesis+and+biological+evaluation+of+analogs+of+NSC+652287%2C+which+targets+the+renal+carcinoma+cell+line+A498.+The+Pd-catalyzed+Suzuki-Miyaura+cross-coupling+with+halogenated+furan%2C+thiophene%2C+and+selenophene+led+to+generally+high+overall+yields+for+the+construction+of+heterocyclic+triads.+C-H+bond+activation+provided+an+efficient+strategy+for+the+Pd-catalyzed+cross-coupling+at+C(2)+of+oxazoles.+Further+analog+variation+was+achieved+with+a+copper-catalyzed+azide-alkyne+cycloaddition+to+form+a+1%2C4-substituted+1%2C2%2C3-triazole.+Potency+and+selectivity+of+the+final+hydroxymethyl+products+were+determined+in+the+NCI-60+cell+assay.+Two+lead+compounds+were+tested+in+vivo+and+compared+to+NSC+652287.+The+evaluation+of+these+compounds+continues+with+a+thermal+shift+assay+coupled+with+differential+mass+spectrometry+for+biological+target+identification.+The+chemical+stability+of+select+triads+are+also+discussed.%0D%0AThe+second+chapter+details+the+synthesis+of+thienopyridone+and+thienopyrimidine+dione+analogs+as+inhibitors+of+protein+tyrosine+phosphatase+4A3+(PTP4A3)%2C+an+attractive+anticancer+target.+Derivatization+by+photooxygenation+led+to+a+compound+with+a+unique+structural+motif%2C+high+potency%2C+and+excellent+selectivity+towards+PTP4A3.+An+automated+synthesis+strategy+using+Lilly%E2%80%99s+Automated+Synthesis+Lab+was+employed+for+analog+synthesis.&rft.date=2017-09-28&rft.type=University+of+Pittsburgh+ETD&rft.type=PeerReviewed&rft.format=application%2Fpdf&rft.language=en&rft.identifier=http%3A%2F%2Fd-scholarship-dev.library.pitt.edu%2F33064%2F1%2Fsalamounjm_etdPitt2017.pdf&rft.identifier=++Salamoun%2C+Joseph+M++(2017)+SYNTHESIS+OF+THIOPHENE-CONTAINING+HETEROCYCLES+AND+THEIR+APPLICATION+AS+ANTICANCER+AGENTS.++Doctoral+Dissertation%2C+University+of+Pittsburgh.++++(Unpublished)++