Download MendeleyA tetrazolyl-substituted subtype-selective AMPA receptor agonist.
Vogensen, S.B., Frydenvang, K., Greenwood, J.R., Postorino, G., Nielsen, B., Pickering, D.S., Ebert, B., Bolcho, U., Egebjerg, J., Gajhede, M., Kastrup, J.S., Johansen, T.N., Clausen, R.P., Krogsgaard-Larsen, P.(2007) J Med Chem 50: 2408-2414
- PubMed: 17455929
- DOI: https://doi.org/10.1021/jm061439q
- Primary Citation of Related Structures:
2P2A - PubMed Abstract:
Replacement of the methyl group of the AMPA receptor agonist 2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA) with a benzyl group provided the first AMPA receptor agonist, compound 7, capable of discriminating GluR2-4 from GluR1 by its more than 10-fold preference for the former receptor subtypes. An X-ray crystallographic analysis of this new analogue in complex with the GluR2-S1S2J construct shows that accommodation of the benzyl group creates a previously unobserved pocket in the receptor, which may explain the remarkable pharmacological profile of compound 7.
Organizational Affiliation:
Department of Medicinal Chemistry, The Faculty of Pharmaceutical Sciences, University of Copenhagen, 2 Universitetsparken, DK-2100 Copenhagen, Denmark.
