{"id":{"repo_id":"duquesne","oai_identifier":"oai:dsc.duq.edu:etd-2429"},"canonical_url":"https://search.dev.ndltd.org/etd/duquesne/oai:dsc.duq.edu:etd-2429","repository":{"repo_id":"duquesne","name":"Duquesne","base_url":"https://dsc.duq.edu/do/oai/"},"display":{"title":"Synthesis of Bicyclic Thieno[2,3-d]Pyrimidines, Tricyclic Thieno[2,3-d]Pyrimidines and Thieno[3,2-d]Pyrimidines as Classical and Nonclassical Antifolates","abstract":"An introduction, background and research progress in the areas of antifolates and antimitotic agents has been reviewed and discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. As a part of this study, thirty-five novel compounds were designed and synthesized on the basis of existing clinically active compounds and their crystal structures. These compounds were synthesized and evaluated as single and/or muliple targeted classical and nonclassical antifolates to decrease toxicity and improve the antitumor activity and selectivity of existing therapeutic agents. In addition, bicyclic substituted thieno[2, 3- italic d /italic ]- and theino[3, 2- italic d /italic ]pyrimidines were synthesized as antimitotic agents. These compounds allowed potent inhibition of tumor cells in culture and extended the structure-activity relationship in the antimitotic area.","abstract_html":"An introduction, background and research progress in the areas of antifolates and antimitotic agents has been reviewed and discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. As a part of this study, thirty-five novel compounds were designed and synthesized on the basis of existing clinically active compounds and their crystal structures. These compounds were synthesized and evaluated as single and/or muliple targeted classical and nonclassical antifolates to decrease toxicity and improve the antitumor activity and selectivity of existing therapeutic agents. In addition, bicyclic substituted thieno[2, 3- italic d /italic ]- and theino[3, 2- italic d /italic ]pyrimidines were synthesized as antimitotic agents. These compounds allowed potent inhibition of tumor cells in culture and extended the structure-activity relationship in the antimitotic area.","abstract_has_math":false,"creators":["Zhou, Xilin"],"institution":null,"degree_name":"MS","degree_level":"Immediate Access","degree_discipline":"Medicinal Chemistry","degree_department":null,"school":null,"contributors":["Aleem Gangjee","Patrick Flaherty","David Lapinsky"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-01-01T08:00:00Z","date_published":"2012-01-01T08:00:00Z","updated_at":"2026-07-24T02:10:43Z","subjects":["Antifolate","Drug design","SAR"],"languages":["English"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://dsc.duq.edu/etd/1413","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Aleem Gangjee","Patrick Flaherty","David Lapinsky"]},{"key":"dc:creator","label":"Author","values":["Zhou, Xilin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2018-03-28T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Medicinal Chemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Immediate Access"]},{"key":"thesis:degree_name","label":"Degree Name","values":["MS"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Antifolate","Drug design","SAR"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://dsc.duq.edu/etd/1413"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["An introduction, background and research progress in the areas of antifolates and antimitotic agents has been reviewed and discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. As a part of this study, thirty-five novel compounds were designed and synthesized on the basis of existing clinically active compounds and their crystal structures. These compounds were synthesized and evaluated as single and/or muliple targeted classical and nonclassical antifolates to decrease toxicity and improve the antitumor activity and selectivity of existing therapeutic agents. In addition, bicyclic substituted thieno[2, 3- italic d /italic ]- and theino[3, 2- italic d /italic ]pyrimidines were synthesized as antimitotic agents. These compounds allowed potent inhibition of tumor cells in culture and extended the structure-activity relationship in the antimitotic area."]},{"key":"dc:title","label":"Title","values":["Synthesis of Bicyclic Thieno[2,3-d]Pyrimidines, Tricyclic Thieno[2,3-d]Pyrimidines and Thieno[3,2-d]Pyrimidines as Classical and Nonclassical Antifolates"]}]}],"canonical_facts":{"dc:contributor":["Aleem Gangjee","Patrick Flaherty","David Lapinsky"],"dc:creator":["Zhou, Xilin"],"dc:date.available":["2018-03-28T07:00:00Z"],"dc:description.abstract":["An introduction, background and research progress in the areas of antifolates and antimitotic agents has been reviewed and discussed. Thymidylate synthase (TS), dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFTase) are important folate dependent enzymes that are targets for cancer chemotherapy and the treatment of infectious diseases. As a part of this study, thirty-five novel compounds were designed and synthesized on the basis of existing clinically active compounds and their crystal structures. These compounds were synthesized and evaluated as single and/or muliple targeted classical and nonclassical antifolates to decrease toxicity and improve the antitumor activity and selectivity of existing therapeutic agents. In addition, bicyclic substituted thieno[2, 3- italic d /italic ]- and theino[3, 2- italic d /italic ]pyrimidines were synthesized as antimitotic agents. These compounds allowed potent inhibition of tumor cells in culture and extended the structure-activity relationship in the antimitotic area."],"dc:identifier":["https://dsc.duq.edu/etd/1413"],"dc:language":["English"],"dc:subject":["Antifolate","Drug design","SAR"],"dc:title":["Synthesis of Bicyclic Thieno[2,3-d]Pyrimidines, Tricyclic Thieno[2,3-d]Pyrimidines and Thieno[3,2-d]Pyrimidines as Classical and Nonclassical Antifolates"],"thesis:degree_discipline":["Medicinal Chemistry"],"thesis:degree_level":["Immediate Access"],"thesis:degree_name":["MS"]},"updated_at":"2026-07-24T02:10:43Z"}