Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues

TY - JOUR

T1 - Synthesis and pharmacological evaluation of conformationally constrained glutamic acid higher homologues

AU - Tamborini, Lucia

AU - Cullia, Gregorio

AU - Nielsen, Birgitte

AU - De Micheli, Carlo

AU - Conti, Paola

AU - Pinto, Andrea

N1 - Copyright © 2016 Elsevier Ltd. All rights reserved.

PY - 2016/11/15

Y1 - 2016/11/15

N2 - 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.

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.

U2 - 10.1016/j.bmc.2016.09.029

DO - 10.1016/j.bmc.2016.09.029

M3 - Journal article

C2 - 27658797

SN - 0968-0896

VL - 24

SP - 5741

EP - 5747

JO - Bioorganic & Medicinal Chemistry

JF - Bioorganic & Medicinal Chemistry

IS - 22

ER -