Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues

Lucia Tamborini; Gregorio Cullia; Birgitte Nielsen; Carlo De Micheli; Paola Conti; Andrea Pinto

doi:10.1016/j.bmc.2016.09.029

Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues

Lucia Tamborini, Gregorio Cullia, Birgitte Nielsen, Carlo De Micheli, Paola Conti, Andrea Pinto

1 Citation (Scopus)

Abstract

Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead for the development of a new class of NMDA antagonists.

Original language	English
Journal	Bioorganic & Medicinal Chemistry
Volume	24
Issue number	22
Pages (from-to)	5741-5747
Number of pages	7
ISSN	0968-0896
DOIs	https://doi.org/10.1016/j.bmc.2016.09.029
Publication status	Published - 15 Nov 2016

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AU - Tamborini, Lucia

AU - Cullia, Gregorio

AU - Nielsen, Birgitte

AU - De Micheli, Carlo

AU - Conti, Paola

AU - Pinto, Andrea

PY - 2016/11/15

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AB - Homologation of glutamic acid chain together with conformational constraint is a commonly used strategy to achieve selectivity towards different types of glutamate receptors. In the present work, starting from two potent and selective unnatural amino acids previously developed by us, we investigated the effects on the activity/selectivity profile produced by a further increase in the distance between the amino acidic moiety and the distal carboxylate group. Interestingly, the insertion of an aromatic ring as a spacer produced a low micromolar affinity NMDA ligand that might represent a lead for the development of a new class of NMDA antagonists.

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DO - 10.1016/j.bmc.2016.09.029

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JO - Bioorganic & Medicinal Chemistry

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ER -

Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues

Abstract

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