Literature DB >> 19692242

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

Satoru Ito1, Yukari Hirata, Yasushi Nagatomi, Atsushi Satoh, Gentaroh Suzuki, Toshifumi Kimura, Akio Satow, Shunsuke Maehara, Hirohiko Hikichi, Mikiko Hata, Hisashi Ohta, Hiroshi Kawamoto.   

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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Year:  2009        PMID： 19692242     DOI： 10.1016/j.bmcl.2009.07.145

Source DB:  PubMed          Journal:  Bioorg Med Chem Lett        ISSN： 0960-894X            Impact factor:   2.823


  8 in total

Review 1.  Comprehensive survey of chemical libraries for drug discovery and chemical biology: 2009.

Authors:  Roland E Dolle; Bertrand Le Bourdonnec; Karin Worm; Guillermo A Morales; Craig J Thomas; Wei Zhang
Journal:  J Comb Chem       Date:  2010-10-05

2.  A novel class of succinimide-derived negative allosteric modulators of metabotropic glutamate receptor subtype 1 provides insight into a disconnect in activity between the rat and human receptors.

Authors:  Hyekyung P Cho; Darren W Engers; Daryl F Venable; Colleen M Niswender; Craig W Lindsley; P Jeffrey Conn; Kyle A Emmitte; Alice L Rodriguez
Journal:  ACS Chem Neurosci       Date:  2014-05-15       Impact factor: 4.418

3.  N-Alkylpyrido[1',2':1,5]pyrazolo-[4,3-d]pyrimidin-4-amines: A new series of negative allosteric modulators of mGlu1/5 with CNS exposure in rodents.

Authors:  Andrew S Felts; Alice L Rodriguez; Ryan D Morrison; Daryl F Venable; Anna L Blobaum; Frank W Byers; J Scott Daniels; Colleen M Niswender; Carrie K Jones; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2016-03-09       Impact factor: 2.823

4.  Triazole Appending Agent (TAAG): A New Synthon for Preparing Iodine-Based Molecular Imaging and Radiotherapy Agents.

Authors:  Alla Darwish; Megan Blacker; Nancy Janzen; Stephanie M Rathmann; Shannon Czorny; Shawn M Hillier; John L Joyal; John W Babich; John F Valliant
Journal:  ACS Med Chem Lett       Date:  2012-02-18       Impact factor: 4.345

5.  Octahydropyrrolo[3,4-c]pyrrole negative allosteric modulators of mGlu1.

Authors:  Jason T Manka; Alice L Rodriguez; Ryan D Morrison; Daryl F Venable; Hyekyung P Cho; Anna L Blobaum; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2013-07-23       Impact factor: 2.823

6.  N-Acyl-N'-arylpiperazines as negative allosteric modulators of mGlu1: identification of VU0469650, a potent and selective tool compound with CNS exposure in rats.

Authors:  Kimberly M Lovell; Andrew S Felts; Alice L Rodriguez; Daryl F Venable; Hyekyung P Cho; Ryan D Morrison; Frank W Byers; J Scott Daniels; Colleen M Niswender; P Jeffrey Conn; Craig W Lindsley; Kyle A Emmitte
Journal:  Bioorg Med Chem Lett       Date:  2013-05-17       Impact factor: 2.823

7.  Synthesis of a library of tricyclic azepinoisoindolinones.

Authors:  Bettina Miller; Shuli Mao; Kara M George Rosenker; Joshua G Pierce; Peter Wipf
Journal:  Beilstein J Org Chem       Date:  2012-07-13       Impact factor: 2.883

8.  Unprecedented selective homogeneous cobalt-catalysed reductive alkoxylation of cyclic imides under mild conditions.

Authors:  Jose R Cabrero-Antonino; Rosa Adam; Veronica Papa; Mattes Holsten; Kathrin Junge; Matthias Beller
Journal:  Chem Sci       Date:  2017-06-12       Impact factor: 9.825
  8 in total

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