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

Basic Information

ID: ALA1155999

Journal: Bioorg Med Chem Lett

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

Authors: Ito S, Hirata Y, Nagatomi Y, Satoh A, Suzuki G, Kimura T, Satow A, Maehara S, Hikichi H, Hata M, Ohta H, Kawamoto H.

Abstract: 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.

CiteXplore: 19692242

DOI: 10.1016/j.bmcl.2009.07.145

Patent ID: