Discovery and biological profile of isoindolinone derivatives as novel metabotropic glutamate receptor 1 antagonists: a potential treatment for psychotic disorders.

@article{Ito2009DiscoveryAB,
  title={Discovery and biological profile of isoindolinone derivatives as novel metabotropic glutamate receptor 1 antagonists: a potential treatment for psychotic disorders.},
  author={Satoru Ito and Yukari Hirata and Yasushi Nagatomi and Atsushi Satoh and Gentaroh Suzuki and Toshifumi Kimura and Akio Satow and Shunsuke Maehara and Hirohiko Hikichi and Mikiko Hata and Hisashi Ohta and Hiroshi Kawamoto},
  journal={Bioorganic & medicinal chemistry letters},
  year={2009},
  volume={19 18},
  pages={5310-3}
}
We describe here the discovery and biological profile of a series of isoindolinone derivatives as developed mGluR1 antagonists. Our combined strategy of rapid parallel synthesis and conventional medicinal optimization successfully led to N-cyclopropyl 22 and N-isopropyl isoindolinone analogs 21 and 23 with improved in vivo DMPK profiles. Moreover the most advanced analog 23 showed an oral antipsychotic-like effect at a dose of 1mg/kg in an animal model.