Investigation of the Phenyl Ring of Imidazoquinolines
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Issue Date
2018-05-31Author
Hunt, Jordan Robert
Publisher
University of Kansas
Format
128 pages
Type
Thesis
Degree Level
M.S.
Discipline
Medicinal Chemistry
Rights
Copyright held by the author.
Metadata
Show full item recordAbstract
The 1H-Imidazo-[4,5-c]quinolines are a class of compounds that are agonists towards Toll-like receptor 7 and 8 (TLR7/8). For example, Imiquimod and Resiquimod have been shown to act as vaccine adjuvants, enhancing antigen-specific antibody production and skewing the immunity towards a Th1 response. Activation of TLR7/8 have been shown to stimulate dendritic cells to secrete cytokines, upregulate costimulatory molecule expression and enhance antigen presentation to T cells. Imidazoquinoline compounds have demonstrated vaccine adjuvant properties in several animal models. The adjuvant effects can be enhanced by measures that localize the drug with the vaccine without quickly entering the systemic circulation. Clinical studies demonstrate that local immune activation is useful; imiquimod is approved for the topical treatment of basal cell carcinomas. However, injection or oral routes of administration of imidazoquinolines are not therapeutically beneficial and possibly dangerous due to systemic and non-specific activation of the immune system. To take advantage of the adjuvant property of imidazoquinolines, they need to be formulated or designed to allow for local immune activation without induction of systemic cytokines. This study focuses on developing a new site on the phenyl ring to lead to better imidazoquinolines that could be easily formulated in future drug delivery studies.
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- Medicinal Chemistry Dissertations and Theses [80]
- Theses [3973]
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