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Title: | Enantiopure Indolo[2,3-a]quinolizidines: Synthesis and Evaluation as NMDA Receptor Antagonists |
Author: | Pereira, Nuno A. L. Sureda, Francesc X. Pérez Bosch, Maria Amat Tusón, Mercedes Santos, Maria M. M. |
Keywords: | Malalties neurodegeneratives Síntesi orgànica Neurodegenerative Diseases Organic synthesis |
Issue Date: | 6-Aug-2016 |
Publisher: | MDPI |
Abstract: | Enantiopure tryptophanol is easily obtained from the reduction of its parent natural amino acid trypthophan (available from the chiral pool), and can be used as chiral auxiliary/inductor to control the stereochemical course of a diastereoselective reaction. Furthermore, enantiopure tryptophanol is useful for the syntheses of natural products or biological active molecules containing the aminoalcohol functionality. In this communication, we report the development of a small library of indolo[2,3-a]quinolizidines and evaluation of their activity as N-Methyl D-Aspartate (NMDA) receptor antagonists. The indolo[2,3-a]quinolizidine scaffold was obtained using the following key steps: (i) a stereoselective cyclocondensation of (S)- or (R)-tryptophanol with appropriate racemic -oxoesters; (ii) a stereocontrolled cyclization on the indole nucleus. The synthesized enantiopure indolo[2,3-a]quinolizidines were evaluated as NMDA receptor antagonists and one compound was identified to be 2.9-fold more potent as NMDA receptor blocker than amantadine (used in the clinic for Parkinson's disease). This compound represents a hit compound for the development of novel NMDA receptor antagonists with potential applications in neurodegenerative disorders associated with overactivation of NMDA receptors. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/molecules21081027 |
It is part of: | Molecules, 2016, vol. 21, num. 8, p. 1027-1039 |
URI: | http://hdl.handle.net/2445/108047 |
Related resource: | https://doi.org/10.3390/molecules21081027 |
ISSN: | 1420-3049 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia) |
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