pyrrolopyrimidine and purine

Mps1, also known as TTK, is a mitotic checkpoint protein kinase that has become a promising new target of cancer research. In an effort to improve the lead-likeness of our recent Mps1 purine lead compounds, a scaffold hopping exercise has been undertaken. Structure-based design, principles of conformational restriction, and subsequent scaffold hopping has led to novel pyrrolopyrimidine and quinazoline Mps1 inhibitors. These new single-digit nanomolar leads provide the basis for developing potent, novel Mps1 inhibitors with improved drug-like properties.

Topics: Cell Cycle Proteins; Cell Proliferation; Drug Design; HCT116 Cells; Humans; Models, Molecular; Protein Binding; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Protein-Tyrosine Kinases; Purines; Pyrimidines; Pyrroles; Quinazolines; Structure-Activity Relationship