Publications by authors named "Oliver R Steward"

In this article, we report the discovery of a series of pyrimidopyridones as inhibitors of IRAK4 kinase. From a previously disclosed 5-azaquinazoline series, we found that switching the pyridine ring for an N-substituted pyridone gave a novel hinge binding scaffold which retained potency against IRAK4. Importantly, introduction of the carbonyl established an internal hydrogen bond with the 4-NH, establishing a conformational lock and allowing truncation of the large basic substituent to a 1-methylcyclopyl group.

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Article Synopsis
  • - This article discusses the enhancement of human drug clearance for a group of compounds known as 5-azaquinazolines through targeted chemical modifications.
  • - Researchers conducted extensive studies on drug metabolism and pharmacokinetics (DMPK) to address issues related to high metabolism by Aldehyde Oxidase and inconsistencies in drug clearance rates observed in liver models.
  • - The efforts led to the identification of a specific compound, 5-azaquinazoline 35, which not only demonstrated strong selectivity for the target IRAK4 but also showed promising combined effects against a particular type of lymphoma when used alongside the drug acalabrutinib.
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