Literature DB >> 30608678

Discovery of an Orally Bioavailable and Central Nervous System (CNS) Penetrant mGlu7 Negative Allosteric Modulator (NAM) in Vivo Tool Compound: N-(2-(1 H-1,2,4-triazol-1-yl)-5-(trifluoromethoxy)phenyl)-4-(cyclopropylmethoxy)-3-methoxybenzamide (VU6012962).

Carson W Reed, Samantha E Yohn, Jordan P Washecheck, Hanna F Roenfanz, Marc C Quitalig, Vincent B Luscombe, Matthew T Jenkins, Alice L Rodriguez, Darren W Engers, Anna L Blobaum, P Jeffrey Conn1, Colleen M Niswender1, Craig W Lindsley.   

Abstract

Herein, we report the discovery of a new, orally bioavailable and CNS-penetrant metabotropic glutamate receptor 7 (mGlu7) negative allosteric modulator (NAM) that achieves exposure in cerebral spinal fluid (CSF) 2.5× above the in vitro IC50 at minimum effective doses (MEDs) of 3 mg/kg in preclinical anxiety models.

Entities:  

Year:  2019        PMID： 30608678      PMCID： PMC6501583          DOI： 10.1021/acs.jmedchem.8b01810

Source DB:  PubMed          Journal:  J Med Chem        ISSN： 0022-2623            Impact factor:   7.446


  7 in total

1.  Discovery of VU6027459: A First-in-Class Selective and CNS Penetrant mGlu7 Positive Allosteric Modulator Tool Compound.

Authors:  Carson W Reed; Jacob J Kalbfleisch; Madison J Wong; Jordan P Washecheck; Ashton Hunter; Alice L Rodriguez; Anna L Blobaum; P Jeffrey Conn; Colleen M Niswender; Craig W Lindsley
Journal:  ACS Med Chem Lett       Date:  2020-08-20       Impact factor: 4.345

Review 2.  Amide Bond Bioisosteres: Strategies, Synthesis, and Successes.

Authors:  Shikha Kumari; Angelica V Carmona; Amit K Tiwari; Paul C Trippier
Journal:  J Med Chem       Date:  2020-08-04       Impact factor: 7.446

Review 3.  The neurobiological basis for novel experimental therapeutics in dystonia.

Authors:  Anthony M Downs; Kaitlyn M Roman; Simone A Campbell; Antonio Pisani; Ellen J Hess; Paola Bonsi
Journal:  Neurobiol Dis       Date:  2019-07-04       Impact factor: 5.996

4.  Blocking Metabotropic Glutamate Receptor Subtype 7 via the Venus Flytrap Domain Promotes a Chronic Stress-Resilient Phenotype in Mice.

Authors:  Karolyne A R Estrela; Lisa Senninger; Josephine Arndt; Melanie Kabas; Ferdinand Schmid; Larissa Dillmann; Sophia Auer; Thomas Stepfer; Peter J Flor; Nicole Uschold-Schmidt
Journal:  Cells       Date:  2022-06-02       Impact factor: 7.666

5.  Synthesis and SAR of a series of mGlu7 NAMs based on an ethyl-8-methoxy-4-(4-phenylpiperazin-1-yl)quinoline carboxylate core.

Authors:  Jacob J Kalbfleisch; Carson W Reed; Charlotte Park; Paul K Spearing; Marc C Quitalig; Matthew T Jenkins; Alice L Rodriguez; Anna L Blobaum; P Jeffrey Conn; Colleen M Niswender; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2020-09-02       Impact factor: 2.823

6.  Classification models and SAR analysis on CysLT1 receptor antagonists using machine learning algorithms.

Authors:  Hongzhao Wang; Zijian Qin; Aixia Yan
Journal:  Mol Divers       Date:  2021-02-03       Impact factor: 3.364

7.  G-alpha interacting protein interacting protein, C terminus 1 regulates epileptogenesis by increasing the expression of metabotropic glutamate receptor 7.

Authors:  Yong Liu; You Wang; Juan Yang; Tao Xu; Changhong Tan; Peng Zhang; Qiankun Liu; Yangmei Chen
Journal:  CNS Neurosci Ther       Date:  2021-10-22       Impact factor: 5.243
  7 in total

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