Efficient synthesis of novel glutamate homologues and investigation of their affinity and selectivity profile at ionotropic glutamate receptors

作者：Pinto Andrea^*; Tamborini Lucia; Mastronardi Federica; Ettari Roberta; Romano Diego; Nielsen Birgitte; De Micheli Carlo; Conti Paola

来源：Bioorganic & Medicinal Chemistry Letters, 2014, 24(8): 1980-1982.

DOI：10.1016/j.bmcl.2014.02.058

• L-Glutamic acid
• N-Methyl-D-aspartate receptor
• Semi-preparative chiral HPLC
• D-Allylglycine
• Heck reaction

A convenient synthesis of four new enantiomerically pure acidic amino acids is reported and their affinity at ionotropic glutamate receptors was determined. The new compounds are higher homologues of glutamic acid in which the molecular complexity has been increased by introducing an aromatic/heteroaromatic ring, that is a phenyl or a thiophene ring, that could give additional electronic interactions with the receptors. The results of the present investigation indicate that the insertion of an aromatic/heteroaromatic ring into the amino acid skeleton of glutamate higher homologues is well tolerated and this modification could be exploited to generate a new class of NMDA antagonists.

• 出版日期2014-4-15