title: Tryptophanol-derived oxazolopiperidone lactams: identification of a hit compound as NMDA receptor antagonist.
abstract: N-Methyl-D-aspartate receptors (NMDAR) exacerbated activation leads to neuron death through a phenomenon called excitotoxicity. These receptors are implicated in several neurological diseases (e.g., Alzheimer and Parkinson) and thus represent an important therapeutic target. We herein describe the study of enantiopure tryptophanol-derived oxazolopiperidone lactams as NMDA receptor antagonists. The most active hit exhibited an IC50 of 63.4 μM in cultured rat cerebellar granule neurons thus being 1.5 fold more active than clinically approved NMDA antagonist amantadine (IC50=92 μM).
authors: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal.
authors: Nuno A L
authors: NA
authors: Pereira
authors: Pharmacology Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, c./St. Llorenç 21, 43201 Reus (Tarragona), Spain.
authors: Francesc X
authors: FX
authors: Sureda
authors: Pharmacology Unit, Faculty of Medicine and Health Sciences, Universitat Rovira i Virgili, c./St. Llorenç 21, 43201 Reus (Tarragona), Spain.
authors: Roser
authors: R
authors: Esplugas
authors: Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, s/n, 08028 Barcelona, Spain.
authors: Maria
authors: M
authors: Pérez
authors: Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, Av. Joan XXIII, s/n, 08028 Barcelona, Spain.
authors: Mercedes
authors: M
authors: Amat
authors: Instituto de Investigação do Medicamento (iMed.ULisboa), Faculdade de Farmácia, Universidade de Lisboa, Av. Prof. Gama Pinto, 1649-003 Lisboa, Portugal. Electronic address: mariasantos@ff.ul.pt.
authors: Maria M M
authors: MM
authors: Santos
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007769:Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D007211:Indoles; D007769:Lactams; D010881:Piperidones; D016194:Receptors, N-Methyl-D-Aspartate; C069544:tryptophanol; D014364:Tryptophan
keywords: N-Methyl-d-aspartate receptors; NMDAR antagonist; Neurodegenerative diseases; Oxazolopiperidones; Tryptophanol