AZ12216052

Last updated
AZ12216052
AZ12216052 structure.png
Identifiers
  • 2-[(4-bromophenyl)methylsulfanyl]-N-(4-butan-2-ylphenyl)acetamide
CAS Number
PubChem CID
ChemSpider
Chemical and physical data
Formula C19H22BrNOS
Molar mass 392.36 g·mol−1
3D model (JSmol)
  • CCC(C)C1=CC=C(C=C1)NC(=O)CSCC2=CC=C(C=C2)Br
  • InChI=1S/C19H22BrNOS/c1-3-14(2)16-6-10-18(11-7-16)21-19(22)13-23-12-15-4-8-17(20)9-5-15/h4-11,14H,3,12-13H2,1-2H3,(H,21,22)
  • Key:QKUYZJOTWYRWNF-UHFFFAOYSA-N

AZ-12216052 is a drug which acts as a potent and selective positive allosteric modulator of the metabotropic glutamate receptor 8, and is used for research into the role of this receptor subtype in various processes including anxiety and neuropathic pain. [1] [2] [3] [4] [5]

Related Research Articles

<span class="mw-page-title-main">Metabotropic glutamate receptor</span> Type of glutamate receptor

The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate receptors, mGluRs bind with glutamate, an amino acid that functions as an excitatory neurotransmitter.

<span class="mw-page-title-main">Glutamate receptor</span> Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells

Glutamate receptors are synaptic and non synaptic receptors located primarily on the membranes of neuronal and glial cells. Glutamate is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.

<span class="mw-page-title-main">Metabotropic glutamate receptor 1</span> Mammalian protein found in humans

The glutamate receptor, metabotropic 1, also known as GRM1, is a human gene which encodes the metabotropic glutamate receptor 1 (mGluR1) protein.

<span class="mw-page-title-main">Metabotropic glutamate receptor 2</span> Mammalian protein found in humans

Metabotropic glutamate receptor 2 (mGluR2) is a protein that, in humans, is encoded by the GRM2 gene. mGluR2 is a G protein-coupled receptor (GPCR) that couples with the Gi alpha subunit. The receptor functions as an autoreceptor for glutamate, that upon activation, inhibits the emptying of vesicular contents at the presynaptic terminal of glutamatergic neurons.

<span class="mw-page-title-main">Metabotropic glutamate receptor 3</span> Mammalian protein found in humans

Metabotropic glutamate receptor 3 (mGluR3) is an inhibitory Gi/G0-coupled G-protein coupled receptor (GPCR) generally localized to presynaptic sites of neurons in classical circuits. However, in higher cortical circuits in primates, mGluR3 are localized post-synaptically, where they strengthen rather than weaken synaptic connectivity. In humans, mGluR3 is encoded by the GRM3 gene. Deficits in mGluR3 signaling have been linked to impaired cognition in humans, and to increased risk of schizophrenia, consistent with their expanding role in cortical evolution.

<span class="mw-page-title-main">Metabotropic glutamate receptor 4</span> Mammalian protein found in humans

Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 5</span> Mammalian protein found in humans

Metabotropic glutamate receptor 5 is an excitatory Gq-coupled G protein-coupled receptor predominantly expressed on the postsynaptic sites of neurons. In humans, it is encoded by the GRM5 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 7</span> Mammalian protein found in humans

Metabotropic glutamate receptor 7 is a protein that in humans is encoded by the GRM7 gene.

<span class="mw-page-title-main">Metabotropic glutamate receptor 8</span> Mammalian protein found in humans

Metabotropic glutamate receptor 8 is a protein that in humans is encoded by the GRM8 gene.

<span class="mw-page-title-main">LY-341495</span> Chemical compound

LY-341495 is a research drug developed by the pharmaceutical company Eli Lilly, which acts as a potent and selective orthosteric antagonist for the group II metabotropic glutamate receptors (mGluR2/3).

<span class="mw-page-title-main">2-Methyl-6-(phenylethynyl)pyridine</span> Chemical compound

2-Methyl-6-(phenylethynyl)pyridine (MPEP) is a research drug which was one of the first compounds found to act as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. After being originally patented as a liquid crystal for LCDs, it was developed by the pharmaceutical company Novartis in the late 1990s. It was found to produce neuroprotective effects following acute brain injury in animal studies, although it was unclear whether these results were purely from mGluR5 blockade as it also acts as a weak NMDA antagonist, and as a positive allosteric modulator of another subtype mGlu4, and there is also evidence for a functional interaction between mGluR5 and NMDA receptors in the same populations of neurons. It was also shown to produce antidepressant and anxiolytic effects in animals, and to reduce the effects of morphine withdrawal, most likely due to direct interaction between mGluR5 and the μ-opioid receptor.

<span class="mw-page-title-main">ADX-47273</span> Chemical compound

ADX-47273 is a research pharmaceutical developed by Addex Therapeutics which acts as a positive allosteric modulator (PAM) selective for the metabotropic glutamate receptor subtype mGluR5. It has nootropic and antipsychotic effects in animal studies, and has been used as a lead compound to develop improved derivatives.

<span class="mw-page-title-main">SIB-1893</span> Chemical compound

SIB-1893 is a drug used in scientific research which was one of the first compounds developed that acts as a selective antagonist for the metabotropic glutamate receptor subtype mGluR5. It has anticonvulsant and neuroprotective effects, and reduces glutamate release. It has also been found to act as a positive allosteric modulator of mGluR4.

<span class="mw-page-title-main">CDPPB</span> Chemical compound

CDPPB is a drug used in scientific research which acts as a positive allosteric modulator selective for the metabotropic glutamate receptor subtype mGluR5. It has antipsychotic effects in animal models, and mGluR5 modulators are under investigation as potential drugs for the treatment of schizophrenia, as well as other applications.

<span class="mw-page-title-main">Ro01-6128</span> Chemical compound

Ro01-6128 is a drug used in scientific research, which acts as a selective positive allosteric modulator for the metabotropic glutamate receptor subtype mGluR1. It was derived by modification of a lead compound found via high-throughput screening, and was further developed to give the improved compound Ro67-4853.

<span class="mw-page-title-main">Ro67-4853</span> Chemical compound

Ro67-4853 is a drug used in scientific research, which acts as a selective positive allosteric modulator for the metabotropic glutamate receptor subtype mGluR1. It was derived by modification of the simpler compound Ro01-6128, and has itself subsequently been used as a lead compound to develop a range of potent and selective mGluR1 positive modulators.

<span class="mw-page-title-main">DCPG</span> Chemical

DCPG ((S)-3,4-DCPG) is a drug used in scientific research, which acts as a potent and subtype-selective agonist for the metabotropic glutamate receptor mGluR8. It has anticonvulsant effects in animal studies, and has also been investigated as a possible treatment for hyperalgesia.

<span class="mw-page-title-main">LY-487,379</span> Chemical compound

LY-487,379 is a drug used in scientific research that acts as a selective positive allosteric modulator for the metabotropic glutamate receptor group II subtype mGluR2. It is used to study the structure and function of this receptor subtype, and LY-487,379 along with various other mGluR2/3 agonists and positive modulators are being investigated as possible antipsychotic and anxiolytic drugs.

<span class="mw-page-title-main">CBiPES</span> Chemical compound

CBiPES is a drug used in scientific research that acts as a selective positive allosteric modulator for the metabotropic glutamate receptor group II subtype mGluR2. It has potentially antipsychotic effects in animal models, and is used for researching the role of mGluR2 receptors in schizophrenia and related disorders.

<span class="mw-page-title-main">LSP2-9166</span> Chemical compound

LSP2-9166 is a drug which acts as a selective agonist for the group III metabotropic glutamate receptors, with a reasonably potent EC50 of 70nM at mGluR4 and 220nM at mGluR7, and weaker activity of 1380nM at mGluR6 and 4800nM at mGluR8. It has anticonvulsant effects in animal studies, and reduces self-administration of various addictive drugs.

References

  1. Duvoisin RM, Pfankuch T, Wilson JM, Grabell J, Chhajlani V, Brown DG, et al. (October 2010). "Acute pharmacological modulation of mGluR8 reduces measures of anxiety". Behavioural Brain Research. 212 (2): 168–173. doi:10.1016/j.bbr.2010.04.006. PMC   2892883 . PMID   20385173.
  2. Reed BT, Morgans CW, Duvoisin RM (April 2013). "Differential modulation of retinal ganglion cell light responses by orthosteric and allosteric metabotropic glutamate receptor 8 compounds". Neuropharmacology. 67: 88–94. doi:10.1016/j.neuropharm.2012.09.023. PMC   3562428 . PMID   23164615.
  3. Rossi F, Marabese I, De Chiaro M, Boccella S, Luongo L, Guida F, et al. (June 2014). "Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses and rostral ventromedial medulla cell activity in neuropathic pain conditions". Journal of Neurophysiology. 111 (11): 2196–2209. doi:10.1152/jn.00212.2013. PMID   24304862.
  4. Jantas D, Greda A, Leskiewicz M, Grygier B, Pilc A, Lason W (September 2015). "Neuroprotective effects of mGluR II and III activators against staurosporine- and doxorubicin-induced cellular injury in SH-SY5Y cells: New evidence for a mechanism involving inhibition of AIF translocation". Neurochemistry International. 88: 124–137. doi:10.1016/j.neuint.2014.12.011. PMID   25661514. S2CID   8865211.
  5. Jantas D, Grygier B, Zatorska J, Lasoń W (October 2018). "Allosteric and Orthosteric Activators of mGluR8 Differentially Affect the Chemotherapeutic-Induced Human Neuroblastoma SH-SY5Y Cell Damage: The Impact of Cell Differentiation State". Basic & Clinical Pharmacology & Toxicology. 123 (4): 443–451. doi: 10.1111/bcpt.13041 . PMID   29753314. S2CID   21666589.