Literature DB >> 32944146

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

Carson W Reed1, Jacob J Kalbfleisch1, Madison J Wong1, Jordan P Washecheck1, Ashton Hunter2, Alice L Rodriguez3,2, Anna L Blobaum3,2, P Jeffrey Conn3,2,4, Colleen M Niswender3,2,4, Craig W Lindsley1,3,2.   

Abstract

Herein, we report the discovery of the first selective and CNS penetrant mGlu7 PAM (VU6027459) derived from a "molecular switch" within a selective mGlu7 NAM chemotype. VU6027459 displayed CNS penetration in both mice (Kp = 2.74) and rats (Kp= 4.78), it was orally bioavailable in rats (%F = 69.5), and undesired activity at DAT was ablated.
Copyright © 2020 American Chemical Society.

Entities:  

Year:  2020        PMID： 32944146      PMCID： PMC7488291          DOI： 10.1021/acsmedchemlett.0c00432

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


  38 in total

1.  Genome-wide copy number variation study associates metabotropic glutamate receptor gene networks with attention deficit hyperactivity disorder.

Authors:  Josephine Elia; Joseph T Glessner; Kai Wang; Nagahide Takahashi; Corina J Shtir; Dexter Hadley; Patrick M A Sleiman; Haitao Zhang; Cecilia E Kim; Reid Robison; Gholson J Lyon; James H Flory; Jonathan P Bradfield; Marcin Imielinski; Cuiping Hou; Edward C Frackelton; Rosetta M Chiavacci; Takeshi Sakurai; Cara Rabin; Frank A Middleton; Kelly A Thomas; Maria Garris; Frank Mentch; Christine M Freitag; Hans-Christoph Steinhausen; Alexandre A Todorov; Andreas Reif; Aribert Rothenberger; Barbara Franke; Eric O Mick; Herbert Roeyers; Jan Buitelaar; Klaus-Peter Lesch; Tobias Banaschewski; Richard P Ebstein; Fernando Mulas; Robert D Oades; Joseph Sergeant; Edmund Sonuga-Barke; Tobias J Renner; Marcel Romanos; Jasmin Romanos; Andreas Warnke; Susanne Walitza; Jobst Meyer; Haukur Pálmason; Christiane Seitz; Sandra K Loo; Susan L Smalley; Joseph Biederman; Lindsey Kent; Philip Asherson; Richard J L Anney; J William Gaynor; Philip Shaw; Marcella Devoto; Peter S White; Struan F A Grant; Joseph D Buxbaum; Judith L Rapoport; Nigel M Williams; Stanley F Nelson; Stephen V Faraone; Hakon Hakonarson
Journal:  Nat Genet       Date:  2011-12-04       Impact factor: 38.330

2.  A selective metabotropic glutamate receptor 7 agonist: activation of receptor signaling via an allosteric site modulates stress parameters in vivo.

Authors:  Kayo Mitsukawa; Rina Yamamoto; Silvio Ofner; Joachim Nozulak; Oliver Pescott; Snezana Lukic; Natacha Stoehr; Cedric Mombereau; Rainer Kuhn; Kevin H McAllister; Herman van der Putten; John F Cryan; Peter J Flor
Journal:  Proc Natl Acad Sci U S A       Date:  2005-12-09       Impact factor: 11.205

3.  Surveying heterocycles as amide bioisosteres within a series of mGlu7 NAMs: Discovery of VU6019278.

Authors:  Carson W Reed; Jordan P Washecheck; Marc C Quitlag; Matthew T Jenkins; Alice L Rodriguez; Darren W Engers; Anna L Blobaum; P Jeffrey Conn; Colleen M Niswender; Craig W Lindsley
Journal:  Bioorg Med Chem Lett       Date:  2019-03-15       Impact factor: 2.823

4.  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).

Authors:  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 Conn; Colleen M Niswender; Craig W Lindsley
Journal:  J Med Chem       Date:  2019-01-17       Impact factor: 7.446

5.  The metabotropic glutamate receptor subtype 7 rs3792452 polymorphism is associated with the response to methylphenidate in children with attention-deficit/hyperactivity disorder.

Authors:  Subin Park; Bung-Nyun Kim; Soo-Churl Cho; Jae-Won Kim; Johanna Inhyang Kim; Min-Sup Shin; Hee-Jeong Yoo; Doug Hyun Han; Jae Hoon Cheong
Journal:  J Child Adolesc Psychopharmacol       Date:  2014-05-09       Impact factor: 2.576

Review 6.  Metabotropic glutamate receptors: physiology, pharmacology, and disease.

Authors:  Colleen M Niswender; P Jeffrey Conn
Journal:  Annu Rev Pharmacol Toxicol       Date:  2010       Impact factor: 13.820

7.  High-resolution chromosome ideogram representation of recognized genes for bipolar disorder.

Authors:  Lindsay N Douglas; Austen B McGuire; Ann M Manzardo; Merlin G Butler
Journal:  Gene       Date:  2016-04-07       Impact factor: 3.688

8.  Characterization of the novel positive allosteric modulator of the metabotropic glutamate receptor 4 ADX88178 in rodent models of neuropsychiatric disorders.

Authors:  Mikhail Kalinichev; Emmanuel Le Poul; Christelle Boléa; Françoise Girard; Brice Campo; Massimiliano Fonsi; Isabelle Royer-Urios; Susan E Browne; Jason M Uslaner; Matthew J Davis; Jacob Raber; Robert Duvoisin; Simon T Bate; Ian J Reynolds; Sonia Poli; Sylvain Celanire
Journal:  J Pharmacol Exp Ther       Date:  2014-06-19       Impact factor: 4.030

9.  Discovery of VU6005649, a CNS Penetrant mGlu7/8 Receptor PAM Derived from a Series of Pyrazolo[1,5-a]pyrimidines.

Authors:  Masahito Abe; Mabel Seto; Rocco G Gogliotti; Matthew T Loch; Katrina A Bollinger; Sichen Chang; Eileen M Engelberg; Vincent B Luscombe; Joel M Harp; Michael Bubser; Darren W Engers; Carrie K Jones; Alice L Rodriguez; Anna L Blobaum; P Jeffrey Conn; Colleen M Niswender; Craig W Lindsley
Journal:  ACS Med Chem Lett       Date:  2017-09-01       Impact factor: 4.345

10.  Altered short-term synaptic plasticity in mice lacking the metabotropic glutamate receptor mGlu7.

Authors:  Trevor J Bushell; Gilles Sansig; Valerie J Collett; Herman van der Putten; Graham L Collingridge
Journal:  ScientificWorldJournal       Date:  2002-03-15
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