Literature DB >> 32184961

Spiro-oxindole Piperidines and 3-(Azetidin-3-yl)-1H-benzimidazol-2-ones as mGlu2 Receptor PAMs.

Ana Isabel de Lucas1, Juan Antonio Vega1, Encarnación Matesanz1, María Lourdes Linares1, Aránzazu García Molina1, Gary Tresadern2, Hilde Lavreysen3, Andrés A Trabanco1, José María Cid1.   

Abstract

Starting from two weak mGlu2 receptor positive allosteric modulator (PAM) HTS hits (4 and 5), a molecular hybridization strategy resulted in the identification of a novel spiro-oxindole piperidine series with improved activity and metabolic stability. Scaffold hopping around the spiro-oxindole core identified the 3-(azetidin-3-yl)-1H-benzimidazol-2-one as bioisoster. Medicinal chemistry optimization of these two novel chemotypes resulted in the identification of potent, selective, orally bioavailable, and brain penetrant mGluR2 PAMs.
Copyright © 2019 American Chemical Society.

Entities:  

Year:  2019        PMID： 32184961      PMCID： PMC7073870          DOI： 10.1021/acsmedchemlett.9b00350

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  21 in total

Review 1.  Ionotropic and metabotropic glutamate receptor structure and pharmacology.

Authors:  James N C Kew; John A Kemp
Journal:  Psychopharmacology (Berl)       Date:  2005-02-25       Impact factor: 4.530

2.  A comparison of ligand based virtual screening methods and application to corticotropin releasing factor 1 receptor.

Authors:  Gary Tresadern; Daniele Bemporad; Trevor Howe
Journal:  J Mol Graph Model       Date:  2009-01-23       Impact factor: 2.518

3.  Molecular Switches of Allosteric Modulation of the Metabotropic Glutamate 2 Receptor.

Authors:  Laura Pérez-Benito; Maarten L J Doornbos; Arnau Cordomí; Luc Peeters; Hilde Lavreysen; Leonardo Pardo; Gary Tresadern
Journal:  Structure       Date:  2017-06-22       Impact factor: 5.006

Review 4.  mGluR2 positive allosteric modulators: a patent review (2009 - present).

Authors:  Andrés A Trabanco; José María Cid
Journal:  Expert Opin Ther Pat       Date:  2013-03-02       Impact factor: 6.674

5.  Discovery of 8-Trifluoromethyl-3-cyclopropylmethyl-7-[(4-(2,4-difluorophenyl)-1-piperazinyl)methyl]-1,2,4-triazolo[4,3-a]pyridine (JNJ-46356479), a Selective and Orally Bioavailable mGlu2 Receptor Positive Allosteric Modulator (PAM).

Authors:  Jose María Cid; Gary Tresadern; Juan Antonio Vega; Ana Isabel de Lucas; Alcira Del Cerro; Encarnación Matesanz; María Lourdes Linares; Aránzazu García; Laura Iturrino; Laura Pérez-Benito; Gregor J Macdonald; Daniel Oehlrich; Hilde Lavreysen; Luc Peeters; Marc Ceusters; Abdellah Ahnaou; Wilhelmus Drinkenburg; Claire Mackie; Marijke Somers; Andrés A Trabanco
Journal:  J Med Chem       Date:  2016-09-09       Impact factor: 7.446

6.  Molecular determinants of positive allosteric modulation of the human metabotropic glutamate receptor 2.

Authors:  A Farinha; H Lavreysen; L Peeters; B Russo; S Masure; A A Trabanco; J Cid; G Tresadern
Journal:  Br J Pharmacol       Date:  2015-02-27       Impact factor: 8.739

7.  Scaffold hopping from pyridones to imidazo[1,2-a]pyridines. New positive allosteric modulators of metabotropic glutamate 2 receptor.

Authors:  Gary Tresadern; Jose María Cid; Gregor J Macdonald; Juan Antonio Vega; Ana Isabel de Lucas; Aránzazu García; Encarnación Matesanz; María Lourdes Linares; Daniel Oehlrich; Hilde Lavreysen; Ilse Biesmans; Andrés A Trabanco
Journal:  Bioorg Med Chem Lett       Date:  2009-11-10       Impact factor: 2.823

8.  Discovery of 1-butyl-3-chloro-4-(4-phenyl-1-piperidinyl)-(1H)-pyridone (JNJ-40411813): a novel positive allosteric modulator of the metabotropic glutamate 2 receptor.

Authors:  José María Cid; Gary Tresadern; Guillaume Duvey; Robert Lütjens; Terry Finn; Jean-Philippe Rocher; Sonia Poli; Juan Antonio Vega; Ana Isabel de Lucas; Encarnación Matesanz; María Lourdes Linares; José Ignacio Andrés; Jesús Alcazar; José Manuel Alonso; Gregor J Macdonald; Daniel Oehlrich; Hilde Lavreysen; Abdelah Ahnaou; Wilhelmus Drinkenburg; Claire Mackie; Stefan Pype; David Gallacher; Andrés A Trabanco
Journal:  J Med Chem       Date:  2014-07-28       Impact factor: 7.446

9.  Preclinical evaluation of the antipsychotic potential of the mGlu2-positive allosteric modulator JNJ-40411813.

Authors:  Hilde Lavreysen; Xavier Langlois; Luc Ver Donck; José María Cid Nuñez; Stefan Pype; Robert Lütjens; Anton Megens
Journal:  Pharmacol Res Perspect       Date:  2015-01-30

10.  Covalent Allosteric Probe for the Metabotropic Glutamate Receptor 2: Design, Synthesis, and Pharmacological Characterization.

Authors:  Maarten L J Doornbos; Xuesong Wang; Sophie C Vermond; Luc Peeters; Laura Pérez-Benito; Andrés A Trabanco; Hilde Lavreysen; José María Cid; Laura H Heitman; Gary Tresadern; Adriaan P IJzerman
Journal:  J Med Chem       Date:  2018-03-07       Impact factor: 7.446
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  1 in total

Review 1.  Put a ring on it: application of small aliphatic rings in medicinal chemistry.

Authors:  Matthias R Bauer; Paolo Di Fruscia; Simon C C Lucas; Iacovos N Michaelides; Jennifer E Nelson; R Ian Storer; Benjamin C Whitehurst
Journal:  RSC Med Chem       Date:  2021-01-07
  1 in total

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