Medicine and Health Sciences Commons^™

Design And Synthesis Of Fused Pyrimidines As Single Agents With Combination Chemotherapy Potential, As Tubulin Polymerization And One-Carbon Metabolism Inhibitors For Cancer, Tasdique Quadery

Electronic Theses and Dissertations

This dissertation describes the design, synthesis, and biological evaluation of bicyclic fused pyrimidines as single agents with combination chemotherapy potential with both antiangiogenic and cytotoxic effects. The dissertation also discusses one-carbon metabolism inhibitors and tumor targeting proteolysis targeting chimeras (PROTACs).

In cancer chemotherapy, the two major limitations are the dose-limiting toxicities of clinically used agents and the development of resistance to the treatment. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with both antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoid …

Design And Synthesis Of Pyrimidine Based Fused Heterocyclics In The Potential Treatment Of Cancer And Opportunistic Infection, Farhana Islam

Electronic Theses and Dissertations

Dose-limiting toxicities of clinically used agents and development of resistance are two significant limitations in cancer chemotherapy. Microtubule targeting agents (MTAs) are a structurally diverse set of compounds that disrupt microtubule dynamics and exert their anticancer effect. Combination chemotherapy with antiangiogenic agents and microtubule targeting agents has shown an advantage against both these drawbacks. Single agents with dual antiangiogenic activity and cytotoxicity would afford a therapy that circumvents pharmacokinetic problems of multiple agents, avoid drug-drug interactions, lower the drug dose, decrease overlapping toxicities, and delay or prevent tumor cell resistance. The work in this dissertation reflects the progress of fused …

Synthesis Of 2,4,6-Substituted Pyrrolo[2,3-D]Pyrimidines As Potential Anticancer Agents, Si Yang

Electronic Theses and Dissertations

This thesis mainly focuses on the introduction of the background and work have been done in the areas of antifolates development, such as folate function, its three uptake mechanisms inside human cells, antifolates’ role in chemotherapy, et. al. In addition, the Structure-Activity-Relationship design rationale for the series of antifolates will also be discussed. Nevertheless, the details of synthesizing these pyrrolo[2,3-d]pyrimidines as potential antifolates have been described, including chemistry reviews on the pyrrolo[2,3-d]pyrimidine scaffold, and the challenges encountered and the solutions how to solve or improve in order to achieve better yield.