Dr. Jennifer Golden
University of Wisconsin
Friday, October 3rd, 2025
12:00 Noon
Room 120 – Meyerhoff Chemistry Building
Host: Dr. Kathie Seley-Radtke
“Quinazolinone-based synthetic strategies leading to antiviral and antiparasitic agent discovery and development”
The quinazolin-4-one pharmacophore appears in natural products and marketed drugs, demonstrating abroad range of architecture-dependent pharmacological activity. Interestingly, the heterocycle also displays unique chemical reactivity, leading to chemical rearrangements that afford products that areotherwise synthetically challenging to access. Following the initial discovery of a quinazolinone rearrangement leading to benzamidine formation, we have developed several synthetic methodsleading to guanidines, N-acylguanidines, ring expanded benzodiazepinones, and uniquely elaborated quinazolinones that are driving preclinical development campaigns. BDGR-49 and BDGR-164 are quinazolinones that show exquisite inhibition of both Venezuelan and eastern equine encephalitisalpha viruses (VEEV and EEEV, respectively) in lethal mouse models, resulting in excellent survival rates.
While these compounds did not exhibit activity against the joint-damaging alphavirus known as Chikungunya Virus (CHIKV), we recently developed quinazolinones that now address this gap, resulting in BDGR-651, which reduced CHIKV titer by > 4 log at 10 mM. These advancements will be discussed.
Lastly, we paired our quinazolinone rearrangement sequence with a Mannich reaction to deliver a modified scaffold that inhibits the highly lethal N. fowleri ‘brain-eating’ amoeba. The chemistry methods and preliminary bioactivity of the series will be highlighted.