Degorce, Sebastien L.; Aagaard, Anna; Anjum, Rana; Cumming, Iain A.; Diene, Coura R.; Fallan, Charlene; Johnson, Tony; Leuchowius, Karl-Johan; Orton, Alexandra L.; Pearson, Stuart; Robb, Graeme R.; Rosen, Alan; Scarfe, Graeme B.; Scott, James S.; Smith, James M.; Steward, Oliver R.; Terstiege, Ina; Tucker, Michael J.; Turner, Paul; Wilkinson, Stephen D.; Wrigley, Gail L.; Xue, Yafeng published their research in Bioorganic & Medicinal Chemistry on December 1 ,2020. The article was titled 《Improving metabolic stability and removing aldehyde oxidase liability in a 5-azaquinazoline series of IRAK4 inhibitors》.Electric Literature of C11H17BN2O2 The article contains the following contents:
In this article, we report our efforts towards improving in vitro human clearance in a series of 5-azaquinazolines through a series of C4 truncations and C2 expansions. Extensive DMPK studies enabled us to tackle high Aldehyde Oxidase (AO) metabolism and unexpected discrepancies in human hepatocyte and liver microsomal intrinsic clearance. Our efforts culminated with the discovery of 5-azaquinazoline I, which also displayed exquisite selectivity for IRAK4, and showed synergistic in vitro activity against MyD88/CD79 double mutant ABC-DLBCL in combination with the covalent BTK inhibitor acalabrutinib. The experimental process involved the reaction of 4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine(cas: 1370001-96-9Electric Literature of C11H17BN2O2)
4-Methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine(cas: 1370001-96-9) belongs to pyrimidine. Pyrimidine nucleotide derivatives have a wide range of biological applications. For example, pyrimidine derivatives are useful in DNA repair studies involving cancer and epigenetics.Electric Literature of C11H17BN2O2
Referemce:
Pyrimidine | C4H4N2 – PubChem,
Pyrimidine – Wikipedia