Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists

Detalhes bibliográficos
Autor(a) principal: Pereira, Nuno A. L.
Data de Publicação: 2013
Outros Autores: Sureda, Francesc X., Turch, M., Amat, Mercedes, Bosch, Joan, Santos, Maria M. M.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/17882
Resumo: N-Methyl-d-aspartate (NMDA) receptor antagonists are known to rescue neuronal cell death caused by excessive activation of glutamate receptors. This phenomenon, known as excitotoxicity, is implicated in the pathogenesis of several neurodegenerative disorders including ischemia, Alzheimer's disease, Parkinson's disease, and Huntington's disease. Unfortunately, some NMDA receptor antagonists have shown discouraging results when tested in clinical trials. However, recent advances in the physiology and pharmacology of the NMDA receptor have kept interest alive in modulating NMDA receptors for therapeutic intervention. We present here the synthesis of a small library of phenylalaninol-derived oxazolopyrrolidone lactams and their evaluation as NMDA receptor antagonists. The compounds were easily synthesized in yields up to 92 %. In addition, one of the compounds has a 50 % inhibitory concentration (IC (50)) of 62 mu M and offers potential to develop more potent NMDA receptor antagonists.
id RCAP_e30d33e2106bad65bab4f3e769b42e76
oai_identifier_str oai:repositorio.ul.pt:10451/17882
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonistsAmino alcoholsChiral auxiliariesNMDA receptor antagonistsPyrrolidonesLactamsN-Methyl-d-aspartate (NMDA) receptor antagonists are known to rescue neuronal cell death caused by excessive activation of glutamate receptors. This phenomenon, known as excitotoxicity, is implicated in the pathogenesis of several neurodegenerative disorders including ischemia, Alzheimer's disease, Parkinson's disease, and Huntington's disease. Unfortunately, some NMDA receptor antagonists have shown discouraging results when tested in clinical trials. However, recent advances in the physiology and pharmacology of the NMDA receptor have kept interest alive in modulating NMDA receptors for therapeutic intervention. We present here the synthesis of a small library of phenylalaninol-derived oxazolopyrrolidone lactams and their evaluation as NMDA receptor antagonists. The compounds were easily synthesized in yields up to 92 %. In addition, one of the compounds has a 50 % inhibitory concentration (IC (50)) of 62 mu M and offers potential to develop more potent NMDA receptor antagonists.Fundação para a Ciência e Tecnologia (Portugal) is acknowledged for financial support (PTDC/QUI-QUI/111664/2009; PEst-OE/SAU/UI4013/2011; REDE/1518/REM/2005). We also thank the Portuguese–Spanish Integrated Action (E-07/11 and AIB2010PT-00324) and the Spanish Ministerio de Ciencia e Innovación (MICINN) (CTQ2009-07021/BQU) for financial support.Repositório da Universidade de LisboaPereira, Nuno A. L.Sureda, Francesc X.Turch, M.Amat, MercedesBosch, JoanSantos, Maria M. M.2015-04-13T15:29:01Z20132013-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/17882engMonatsh Chem (2013) 144:473–477http://dx.doi.org/10.1007/s00706-012-0880-8info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:53:34Zoai:repositorio.ul.pt:10451/17882Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:33:33.257741Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
title Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
spellingShingle Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
Pereira, Nuno A. L.
Amino alcohols
Chiral auxiliaries
NMDA receptor antagonists
Pyrrolidones
Lactams
title_short Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
title_full Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
title_fullStr Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
title_full_unstemmed Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
title_sort Synthesis of phenylalaninol-derived oxazolopyrrolidone lactams and evaluation as NMDA receptor antagonists
author Pereira, Nuno A. L.
author_facet Pereira, Nuno A. L.
Sureda, Francesc X.
Turch, M.
Amat, Mercedes
Bosch, Joan
Santos, Maria M. M.
author_role author
author2 Sureda, Francesc X.
Turch, M.
Amat, Mercedes
Bosch, Joan
Santos, Maria M. M.
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Pereira, Nuno A. L.
Sureda, Francesc X.
Turch, M.
Amat, Mercedes
Bosch, Joan
Santos, Maria M. M.
dc.subject.por.fl_str_mv Amino alcohols
Chiral auxiliaries
NMDA receptor antagonists
Pyrrolidones
Lactams
topic Amino alcohols
Chiral auxiliaries
NMDA receptor antagonists
Pyrrolidones
Lactams
description N-Methyl-d-aspartate (NMDA) receptor antagonists are known to rescue neuronal cell death caused by excessive activation of glutamate receptors. This phenomenon, known as excitotoxicity, is implicated in the pathogenesis of several neurodegenerative disorders including ischemia, Alzheimer's disease, Parkinson's disease, and Huntington's disease. Unfortunately, some NMDA receptor antagonists have shown discouraging results when tested in clinical trials. However, recent advances in the physiology and pharmacology of the NMDA receptor have kept interest alive in modulating NMDA receptors for therapeutic intervention. We present here the synthesis of a small library of phenylalaninol-derived oxazolopyrrolidone lactams and their evaluation as NMDA receptor antagonists. The compounds were easily synthesized in yields up to 92 %. In addition, one of the compounds has a 50 % inhibitory concentration (IC (50)) of 62 mu M and offers potential to develop more potent NMDA receptor antagonists.
publishDate 2013
dc.date.none.fl_str_mv 2013
2013-01-01T00:00:00Z
2015-04-13T15:29:01Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/17882
url http://hdl.handle.net/10451/17882
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Monatsh Chem (2013) 144:473–477
http://dx.doi.org/10.1007/s00706-012-0880-8
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134229368406016

Registros relacionados