pyrrolopyrimidine and Lymphoma--Large-B-Cell--Diffuse

Herein we report the optimization of a series of pyrrolopyrimidine inhibitors of interleukin-1 receptor associated kinase 4 (IRAK4) using X-ray crystal structures and structure based design to identify and optimize our scaffold. Compound 28 demonstrated a favorable physicochemical and kinase selectivity profile and was identified as a promising in vivo tool with which to explore the role of IRAK4 inhibition in the treatment of mutant MYD88

Topics: Administration, Oral; Animals; Antineoplastic Agents; Cell Line, Tumor; Crystallography, X-Ray; Dogs; Female; Humans; Interleukin-1 Receptor-Associated Kinases; Lymphoma, Large B-Cell, Diffuse; Magnetic Resonance Spectroscopy; Male; Mice, SCID; Mutation; Myeloid Differentiation Factor 88; Protein Kinase Inhibitors; Pyrimidines; Pyrroles; Rats, Wistar; Structure-Activity Relationship; Xenograft Model Antitumor Assays