Discovery of novel chiral diazepines as bombesin receptor subtype-3 (BRS-3) agonists with low brain penetration

Bioorg Med Chem Lett. 2014 Feb 1;24(3):750-5. doi: 10.1016/j.bmcl.2013.12.106. Epub 2014 Jan 2.

Abstract

The discovery and optimization of a novel series of BRS-3 agonists are described. We explored a potent BRS-3 agonist with low brain penetration to avoid an adverse effect derived from central nervous system exposure. Through the derivatization process, chiral diazepines 9f and 9g were identified as possessing low brain penetration as well as potent in vitro activity against human and mouse BRS-3s.

Keywords: Bombesin receptor subtype-3 (BRS-3) agonists; Brain penetration; Diazepine.

MeSH terms

  • Animals
  • Azepines / chemical synthesis*
  • Azepines / metabolism
  • Azepines / pharmacology
  • Blood-Brain Barrier*
  • Brain / drug effects
  • Cells, Cultured
  • Humans
  • Mice
  • Molecular Structure
  • Receptors, Bombesin / agonists*
  • Structure-Activity Relationship

Substances

  • Azepines
  • Receptors, Bombesin
  • bombesin receptor subtype 3