Optimization of 2,4-diamino-5-fluoropyrimidine derivatives as protein kinase C theta inhibitors with mitigated time-dependent drug–drug interactions and P-gp liability

Add time:08/14/2019    Source:sciencedirect.com

Protein kinase C theta (PKCθ) plays a critical role in T cell signaling and has therapeutic potential for T cell-mediated diseases such as transplant rejection and rheumatoid arthritis. Here, a series of 2,4-diamino-5-fluoropyrimidine derivatives were prepared and evaluated for their inhibition of PKCθ. Of these compounds, 14f was found to exhibit potent PKCθ inhibitory activity and significantly weak CYP3A4 time-dependent inhibition (TDI) and P-glycoprotein (P-gp) liability.

We also recommend Trading Suppliers and Manufacturers of 2,4-diamino-5-(4-fluoro-3-nitrophenyl)-6-ethylpyrimidine (cas 113494-35-2). Pls Click Website Link as below: cas 113494-35-2 suppliers

Prev:PaperProduction of a group-specific antibody to 1α,25-dihydroxyvitamin D and its derivatives having the 1α,3β-dihydroxylated A-ring structure
Next:Diimidazo[4,5-b:4′,5′-e]pyridine: synthesis and nucleophilic aromatic substitution reaction)