title: 3-Carboxy-pyrazolinalanine as a new scaffold for developing potent and selective NMDA receptor antagonists.
abstract: A synthetic method for the preparation of suitably protected 3-carboxy-Δ2-pyrazolin-5-yl-alanine was developed. This scaffold is amenable to further decoration at the N1 position and was used to generate novel NMDA receptor ligands. Although weaker than the previously reported N1-Ph derivatives, the new ligands retain the ability to selectively bind to NMDA receptor with micromolar to submicromolar affinity. Considering the relevance of the N-functionalization for the biological activity, the results presented in this communication are preliminary to a full SAR study of this novel class of NMDA receptor antagonists.
authors: Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy. Electronic address: lucia.tamborini@unimi.it.
authors: Lucia
authors: L
authors: Tamborini
authors: Andrea
authors: A
authors: Pinto
authors: Federica
authors: F
authors: Mastronardi
authors: Maria C
authors: MC
authors: Iannuzzi
authors: Gregorio
authors: G
authors: Cullia
authors: Birgitte
authors: B
authors: Nielsen
authors: Carlo
authors: C
authors: De Micheli
authors: Paola
authors: P
authors: Conti
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008024:Ligands; D015394:Molecular Structure; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry*; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*
chemical_list: D000814:Aniline Compounds; D008024:Ligands; D011720:Pyrazoles; D016194:Receptors, N-Methyl-D-Aspartate; C023650:aniline
keywords: Amino acid; Intramolecular cyclization; N-Methyl-d-aspartate receptor antagonist; Pyrazoline; l-Glutamic acid