AI Article Synopsis
- * The new compound BKI-1649, featuring a unique pyrrolopyrimidine scaffold, has demonstrated better effectiveness in mouse models at lower doses than earlier pyrazolopyrimidine variants.
- * Two derivatives, BKI-1812 and BKI-1814, were tested and showed enhanced potency compared to previous BKIs, while maintaining similar levels of toxicity and efficacy as their pyrazolopyrimidine counterparts.
Article Abstract
Bumped kinase inhibitors (BKIs) that target calcium-dependent protein kinase 1 have been well established as potential drug candidates against cryptosporidiosis. Recently, BKI-1649, with a 7-pyrrolo[2,3-]pyrimidin-4-amine, or "pyrrolopyrimidine", central scaffold, has shown improved efficacy in mouse models of at substantially reduced doses compared to previously explored analogs of the pyrazolopyrimidine scaffold. Here, two pyrrolopyrimidines with varied substituent groups, BKI-1812 and BKI-1814, were explored in several in vitro and in vivo models and show improvements in potency over the previously utilized pyrazolopyrimidine bumped kinase inhibitors while maintaining equivalent results in other key properties, such as toxicity and efficacy, with their pyrazolopyrimidine isosteric counterparts.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8559537 | PMC |
| http://dx.doi.org/10.1021/acsinfecdis.0c00803 | DOI Listing |
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