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

Bioorg Med Chem Lett. 2014 Dec 1;24(23):5493-6. doi: 10.1016/j.bmcl.2014.10.003. Epub 2014 Oct 12.

Abstract

2-Aminopyrimidin-4(1H)-one was proposed as the novel bioisostere of urea. Bioisosteric replacement of the reported urea series of the CXCR2 antagonists with 2-aminopyrimidin-4(1H)-ones led to the discovery of the novel and potent CXCR2 antagonist 3e. 2-Aminopyrimidin-4(1H)-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.

Keywords: 2-Aminopyrimidin-4(1H)-one; Bioisostere; CXCR2 antagonists; Urea.

MeSH terms

  • Humans
  • Molecular Structure
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Receptors, Interleukin-8B / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Urea / analogs & derivatives*

Substances

  • Pyrimidines
  • Receptors, Interleukin-8B
  • Urea