Synthesis and SAR of novel, non-MPEP chemotype mGluR5 NAMs identified by functional HTS
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چکیده
منابع مشابه
Morphine conditioned reward is inhibited by MPEP, the mGluR5 antagonist.
In the present study we examined the effect of MPEP [2-methyl-6-(phenylethynyl)-pyridine] a potent, selective and systemically active metabotropic glutamate receptor (mGluR) type I (subtype mGluR5) antagonist on conditioned morphine reward in mice. In an unbiased version of conditioned place preference (CPP) paradigm, single conditioning with 10 mg/kg of morphine produced reliable place prefere...
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Potential antipsychotic effects of a selective non-competitive antagonist of metabotropic glutamate receptor 5 (mGluR5), 2-methyl-6-phenylethynylpyridine (MPEP), was examined in two commonly used screening tests: (1) the hyperactivity induced by an NMDA receptor antagonist phencyclidine (PCP), and (2) the hyperactivity induced by an indirect dopamine agonist, D-amphetamine. PCP was administered...
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Sequential cycloisomerizations of diynyl o-benzaldehyde substrates to access novel polycyclic cyclopropanes are reported. The reaction sequence involves initial Cu(I)-mediated cycloisomerization/nucleophilic addition to an isochromene followed by diastereoselective Pt(II)-catalyzed enyne cycloisomerization.
متن کاملSynthesis, SAR and unanticipated pharmacological profiles of analogues of the mGluR5 ago-potentiator ADX-47273.
An iterative analogue library synthesis strategy rapidly developed comprehensive SAR for the mGluR5 ago-potentiator ADX-47273. This effort identified key substituents in the 3-position of oxadiazole that engendered either mGluR5 ago-potentiation or pure mGluR5 positive allosteric modulation. The mGluR5 positive allosteric modulators identified possessed the largest fold shifts (up to 27.9-fold)...
متن کاملNegative Allosteric Modulators of Metabotropic Glutamate Receptors Subtype 5 in Addiction: a Therapeutic Window
BACKGROUND Abundant evidence at the anatomical, electrophysiological, and molecular levels implicates metabotropic glutamate receptor subtype 5 (mGluR5) in addiction. Consistently, the effects of a wide range of doses of different mGluR5 negative allosteric modulators (NAMs) have been tested in various animal models of addiction. Here, these studies were subjected to a systematic review to find...
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ژورنال
عنوان ژورنال: Bioorganic & Medicinal Chemistry Letters
سال: 2009
ISSN: 0960-894X
DOI: 10.1016/j.bmcl.2009.10.059