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

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

  • Bioorg Med Chem Lett. 2009 Sep 15;19(18):5310-3. doi: 10.1016/j.bmcl.2009.07.145.
Satoru Ito 1,  Yukari Hirata,  Yasushi Nagatomi,  Atsushi Satoh,  Gentaroh Suzuki,  Toshifumi Kimura,  Akio Satow,  Shunsuke Maehara,  Hirohiko Hikichi,  Mikiko Hata,  Hisashi Ohta,  Hiroshi Kawamoto
Affiliations

Affiliation

  • 1 Tsukuba Research Institute, Banyu Pharmaceutical CO., Ltd, 3 Okubo, Tsukuba 300-2611, Japan. satoru_ito@merck.com
PMID: 19692242 DOI: 10.1016/j.bmcl.2009.07.145
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.

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