Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1395449 | European Journal of Medicinal Chemistry | 2007 | 10 Pages |
Twelve novel conformationally constrained homologues of glutamic acid have been synthesized and pharmacologically characterized at ionotropic glutamate receptors (iGluRs). Synthesis of the target compounds involved 1,3-dipolar cycloaddition of nitrile oxides to suitable dipolarophiles. The structure to the compounds has been assigned by 1H NMR and, in the case of derivatives (±)-4a, (±)-4b, (±)-5a, and (±)-5b, by means of an X-ray crystallographic analysis carried out on intermediate (±)-12a. The synthesized amino acids were found to be without affinity (Ki/IC50 > 100 μM) for iGluRs with the exception of compounds (±)-4b and (±)-5b, which showed a modest affinity for NMDA receptors (Ki = 34 and 13 μM, respectively). The results indicate that the increased conformational constraints introduced by the cyclopropane ring and the spiro-attached proline ring are both detrimental to the pharmacological activity.
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