2-Aminopyrimidin-4(1H)-one as the novel bioisostere of urea: Discovery of novel and potent CXCR2 antagonists

Abstract 2-Aminopyrimidin-4(1 H )-one was proposed as the novel bioisostere of urea. Bioisosteric replacement of the reported urea series of the CXCR2 antagonists with 2-aminopyrimidin-4(1 H )-ones led to the discovery of the novel and potent CXCR2 antagonist 3e . 2-Aminopyrimidin-4(1 H )-one derivative 3e demonstrated a good developability profile (reasonable solubility and high permeability) and superior chemical stability especially in simulated gastric fluid (SGF) compared with ureas.