Drug discovery contains many strategies, one of which is the privileged scaffold strategy. This strategy incorporates a similar molecular framework within a collection of drug-like compounds in order to target various receptors. These scaffolds are useful to drug discovery scientists since they assist in developing libraries as well as demonstrating selectivity to a target. Oxazolidinones are 5-membered heterocyclic compound containing an oxygen, a nitrogen, and a carbonyl within the ring system. In this present study, the oxazolidinone structure was utilized as a privileged scaffold to target serotonin receptor 7 (5-HT7), mutated BRAF kinase (BRAFV6000E), Bruton’s tyrosine kinase (BTK), and Cyclin-dependent protein kinase 4 and 6 (CDK4/6). Aryl piperazines and piperidines were integrated as another privileged scaffold to support the selectivity towards 5-HT7, while aminopyrimidines were employed to increase binding against the kinases. The 5-HT7 oxazolidinone series was successfully synthesized and analyzed against 5-HT7; however, the three kinase oxazolidinone series were not successfully synthesized.Candidemia is the most common bloodstream infection in the U.S. and is associated with high patient mortality rates. Due to prolonged and/or repeated clinical use of current antifungal agents, drug-resistant fungi have become an emerging problem. There is a need for new antifungals to assist in overcoming drug resistant fungi. In the second project outlined in this work, a series of ketoconazole analogs were designed and successfully synthesized. The ketoconazole analogs exhibited antifungal activity; however, no clear trends were observed in this series. Overall, the series exhibited less CYP3A4 inhibition than the parent compound, ketoconazole. / Pharmaceutical Sciences
| Identifer | oai:union.ndltd.org:TEMPLE/oai:scholarshare.temple.edu:20.500.12613/8317 |
| Date | January 2022 |
| Creators | Day, Brian M. |
| Contributors | Canney, Daniel J., Blass, Benjamin E., Nagar, Swati |
| Publisher | Temple University. Libraries |
| Source Sets | Temple University |
| Language | English |
| Detected Language | English |
| Type | Thesis/Dissertation, Text |
| Format | 44 pages |
| Rights | IN COPYRIGHT- This Rights Statement can be used for an Item that is in copyright. Using this statement implies that the organization making this Item available has determined that the Item is in copyright and either is the rights-holder, has obtained permission from the rights-holder(s) to make their Work(s) available, or makes the Item available under an exception or limitation to copyright (including Fair Use) that entitles it to make the Item available., http://rightsstatements.org/vocab/InC/1.0/ |
| Relation | http://dx.doi.org/10.34944/dspace/8288, Theses and Dissertations |
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