3r7x

Crystal Structure Analysis of a Quinazolinedione sulfonamide bound to human GluR2: A Novel Class of Competitive AMPA Receptor Antagonists with Oral Activity

Structural highlights

3r7x is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.1Å
Ligands:	GLU, QSN
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GRIA2_HUMAN Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.^[1]

Publication Abstract from PubMed

Quinazoline-2,4-diones with a sulfonamide group attached to the N(3) ring atom constitute a novel class of competitive AMPA receptor antagonists. One of the synthesized compounds, 28, shows nanomolar receptor affinity, whereas other examples of the series display oral anticonvulsant activity in animal models.

Quinazolinedione sulfonamides: A novel class of competitive AMPA receptor antagonists with oral activity.,Koller M, Lingenhoehl K, Schmutz M, Vranesic IT, Kallen J, Auberson YP, Carcache DA, Mattes H, Ofner S, Orain D, Urwyler S Bioorg Med Chem Lett. 2011 Apr 8. PMID:21531559^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Ward SE, Harries M, Aldegheri L, Andreotti D, Ballantine S, Bax BD, Harris AJ, Harker AJ, Lund J, Melarange R, Mingardi A, Mookherjee C, Mosley J, Neve M, Oliosi B, Profeta R, Smith KJ, Smith PW, Spada S, Thewlis KM, Yusaf SP. Discovery of N-[(2S)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfo namide, a Novel Clinical AMPA Receptor Positive Modulator. J Med Chem. 2010 Jul 8. PMID:20614889 doi:10.1021/jm1005429
↑ Koller M, Lingenhoehl K, Schmutz M, Vranesic IT, Kallen J, Auberson YP, Carcache DA, Mattes H, Ofner S, Orain D, Urwyler S. Quinazolinedione sulfonamides: A novel class of competitive AMPA receptor antagonists with oral activity. Bioorg Med Chem Lett. 2011 Apr 8. PMID:21531559 doi:10.1016/j.bmcl.2011.04.017

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OCA

[1] Ward SE, Harries M, Aldegheri L, Andreotti D, Ballantine S, Bax BD, Harris AJ, Harker AJ, Lund J, Melarange R, Mingardi A, Mookherjee C, Mosley J, Neve M, Oliosi B, Profeta R, Smith KJ, Smith PW, Spada S, Thewlis KM, Yusaf SP. Discovery of N-[(2S)-5-(6-Fluoro-3-pyridinyl)-2,3-dihydro-1H-inden-2-yl]-2-propanesulfo namide, a Novel Clinical AMPA Receptor Positive Modulator. J Med Chem. 2010 Jul 8. PMID:20614889 doi:10.1021/jm1005429

[2] Koller M, Lingenhoehl K, Schmutz M, Vranesic IT, Kallen J, Auberson YP, Carcache DA, Mattes H, Ofner S, Orain D, Urwyler S. Quinazolinedione sulfonamides: A novel class of competitive AMPA receptor antagonists with oral activity. Bioorg Med Chem Lett. 2011 Apr 8. PMID:21531559 doi:10.1016/j.bmcl.2011.04.017

[1]

[2]

3r7x

Crystal Structure Analysis of a Quinazolinedione sulfonamide bound to human GluR2: A Novel Class of Competitive AMPA Receptor Antagonists with Oral Activity

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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