Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central
Autor(a) principal: | |
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Data de Publicação: | 2006 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Repositório Institucional da Universidade Federal Fluminense (RIUFF) |
Texto Completo: | https://app.uff.br/riuff/handle/1/21031 |
Resumo: | Three novel amidines containing the 1,2,3- and 1,2,4-triazole moiety with potential NMDA/ NR2B antagonist activities in the central nervous system were synthesized: N-(5- trifluormethyl-2H-[1,2,4]-triazole-3-yl)-benzamidine (II), N-benzyl-2-phenyl-2H-[1,2,3]-4- carboxamidine (III) and 2-phenyl-N-(5-trifluormethyl-2H-[1,2,4]-triazole-3-yl)-2H-[1,2,3]- triazole-4-carboxamidine (IV). While amidine II has been prepared from reaction of benzonitrile and 3-amino-5- trifluormethyl-1H-1,2,4-triazole (2) promoted by CuCl at 80oC, the compounds III and IV were prepared from reactions of the 2-phenyl-2H-[1,2,3]-triazole-4-carbonitrile (5) with the appropriate amines, namely benzylamine or amine 2, respectively. In the syntheses II, III and IV carried out by sonication, faster reactions were obtained without loose of chemical yield. Biological activity of the prepared compounds was measured in purified cultures of retinal neurons and photoreceptors. Initial experiments showed that amidines II and III have neuroprotective effects without themselves inducing neurotoxicity. Pretreatment of cultures with amidines II and III inhibited the cell death induced by glutamate: neurotoxicity was reduced by 48 or 60% when amidine II or amidine III, respectively, was present during glutamate exposure. |
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Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso CentralSYNTHESIS OF NEW AMIDINES TRIAZOLES WITH POTENTIAL ANTAGONISTIC ACTIVITIES OF THE NMDA SUBTYPE NR2B IN CENTRAL NERVOUS SYSTEMAmidinasSistema nervoso centralDoenças neurodegenerativasExcitoxicidadeAntagonistas NR2BAmidinas triazólicasAmidinesCentral Nervous SystemCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICAThree novel amidines containing the 1,2,3- and 1,2,4-triazole moiety with potential NMDA/ NR2B antagonist activities in the central nervous system were synthesized: N-(5- trifluormethyl-2H-[1,2,4]-triazole-3-yl)-benzamidine (II), N-benzyl-2-phenyl-2H-[1,2,3]-4- carboxamidine (III) and 2-phenyl-N-(5-trifluormethyl-2H-[1,2,4]-triazole-3-yl)-2H-[1,2,3]- triazole-4-carboxamidine (IV). While amidine II has been prepared from reaction of benzonitrile and 3-amino-5- trifluormethyl-1H-1,2,4-triazole (2) promoted by CuCl at 80oC, the compounds III and IV were prepared from reactions of the 2-phenyl-2H-[1,2,3]-triazole-4-carbonitrile (5) with the appropriate amines, namely benzylamine or amine 2, respectively. In the syntheses II, III and IV carried out by sonication, faster reactions were obtained without loose of chemical yield. Biological activity of the prepared compounds was measured in purified cultures of retinal neurons and photoreceptors. Initial experiments showed that amidines II and III have neuroprotective effects without themselves inducing neurotoxicity. Pretreatment of cultures with amidines II and III inhibited the cell death induced by glutamate: neurotoxicity was reduced by 48 or 60% when amidine II or amidine III, respectively, was present during glutamate exposure.Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorNeste trabalho foram sintetizadas três novas amidinas portadoras dos sistemas 1,2,3- e 1,2,4-triazol com potenciais atividades antagonistas do NMDA subtipo NR2B no sistema nervoso central: N-(5-trifluorometil-2H-[1,2,4]-triazol-3-il)-benzamidina (II), N-benzil-2- fenil-2H-[1,2,3]-4-carboxamidina (III) e 2-fenil-N-(5-trifluorometil-2H-[1,2,4]-triazol-3- il)-2H-[1,2,3]-triazol-4-carboxamidina (IV). Enquanto a amidina II foi preparada a partir da reação entre a benzonitrila e o 3- amino-5-trifluorometil-1H-1,2,4-triazol (2) promovida por CuCl a 80oC, as amidinas III e IV foram obtidas a partir das reações entre a 2-fenil-2H-[1,2,3]-triazol-4-carbonitrila (5) e a benzilamina e a amina 2, respectivamente. Quando as preparações de II, III e IV foram efetuadas empregando-se sonicação, observou-se uma redução considerável do tempo reacional sem prejuízo dos rendimentos químicos. Os ensaios farmacológicos preliminares indicaram que as amidinas triazólicas II e III possuem efeito neuroprotetor por pré-condicionamento. As amidinas II e III não apresentaram efeito neurotóxico quando incubadas em culturas purificadas de neurônios e fotorreceptores de embrião de pinto, mostrando-se efetivas na redução da excitotoxicidade mediada pelo glutamato. Culturas pré-tratadas com a amidina II tiveram um aumento da sobrevida neuronal em 48% quando comparadas a culturas expostas apenas ao glutamato, enquanto que o pré-condicionamento com a amidina III levou a um aumento da sobrevida neuronal em 60%.Programa de Pós-graduação em Química OrgânicaQuímica OrgânicaPinheiro, SérgioCPF:55578249076http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4780190U2Bernardino, Alice Maria RolimCPF:36505404791http://lattes.cnpq.br/6370709289392476Dias, Ayres GuimarãesCPF:43210987654http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4780192J6Marins, Luana Monteiro Spíndola2021-03-10T20:51:48Z2007-03-122021-03-10T20:51:48Z2006-03-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttps://app.uff.br/riuff/handle/1/21031porCC-BY-SAinfo:eu-repo/semantics/embargoedAccessreponame:Repositório Institucional da Universidade Federal Fluminense (RIUFF)instname:Universidade Federal Fluminense (UFF)instacron:UFF2021-03-10T20:51:48Zoai:app.uff.br:1/21031Repositório InstitucionalPUBhttps://app.uff.br/oai/requestriuff@id.uff.bropendoar:21202024-08-19T11:09:18.690587Repositório Institucional da Universidade Federal Fluminense (RIUFF) - Universidade Federal Fluminense (UFF)false |
dc.title.none.fl_str_mv |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central SYNTHESIS OF NEW AMIDINES TRIAZOLES WITH POTENTIAL ANTAGONISTIC ACTIVITIES OF THE NMDA SUBTYPE NR2B IN CENTRAL NERVOUS SYSTEM |
title |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central |
spellingShingle |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central Marins, Luana Monteiro Spíndola Amidinas Sistema nervoso central Doenças neurodegenerativas Excitoxicidade Antagonistas NR2B Amidinas triazólicas Amidines Central Nervous System CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA |
title_short |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central |
title_full |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central |
title_fullStr |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central |
title_full_unstemmed |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central |
title_sort |
Síntese de novas amidinas triazólicas com potenciais antagonistas do NMDA subtipo NR2B no Sistema Nervoso Central |
author |
Marins, Luana Monteiro Spíndola |
author_facet |
Marins, Luana Monteiro Spíndola |
author_role |
author |
dc.contributor.none.fl_str_mv |
Pinheiro, Sérgio CPF:55578249076 http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4780190U2 Bernardino, Alice Maria Rolim CPF:36505404791 http://lattes.cnpq.br/6370709289392476 Dias, Ayres Guimarães CPF:43210987654 http://genos.cnpq.br:12010/dwlattes/owa/prc_imp_cv_int?f_cod=K4780192J6 |
dc.contributor.author.fl_str_mv |
Marins, Luana Monteiro Spíndola |
dc.subject.por.fl_str_mv |
Amidinas Sistema nervoso central Doenças neurodegenerativas Excitoxicidade Antagonistas NR2B Amidinas triazólicas Amidines Central Nervous System CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA |
topic |
Amidinas Sistema nervoso central Doenças neurodegenerativas Excitoxicidade Antagonistas NR2B Amidinas triazólicas Amidines Central Nervous System CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA |
description |
Three novel amidines containing the 1,2,3- and 1,2,4-triazole moiety with potential NMDA/ NR2B antagonist activities in the central nervous system were synthesized: N-(5- trifluormethyl-2H-[1,2,4]-triazole-3-yl)-benzamidine (II), N-benzyl-2-phenyl-2H-[1,2,3]-4- carboxamidine (III) and 2-phenyl-N-(5-trifluormethyl-2H-[1,2,4]-triazole-3-yl)-2H-[1,2,3]- triazole-4-carboxamidine (IV). While amidine II has been prepared from reaction of benzonitrile and 3-amino-5- trifluormethyl-1H-1,2,4-triazole (2) promoted by CuCl at 80oC, the compounds III and IV were prepared from reactions of the 2-phenyl-2H-[1,2,3]-triazole-4-carbonitrile (5) with the appropriate amines, namely benzylamine or amine 2, respectively. In the syntheses II, III and IV carried out by sonication, faster reactions were obtained without loose of chemical yield. Biological activity of the prepared compounds was measured in purified cultures of retinal neurons and photoreceptors. Initial experiments showed that amidines II and III have neuroprotective effects without themselves inducing neurotoxicity. Pretreatment of cultures with amidines II and III inhibited the cell death induced by glutamate: neurotoxicity was reduced by 48 or 60% when amidine II or amidine III, respectively, was present during glutamate exposure. |
publishDate |
2006 |
dc.date.none.fl_str_mv |
2006-03-10 2007-03-12 2021-03-10T20:51:48Z 2021-03-10T20:51:48Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
https://app.uff.br/riuff/handle/1/21031 |
url |
https://app.uff.br/riuff/handle/1/21031 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
CC-BY-SA info:eu-repo/semantics/embargoedAccess |
rights_invalid_str_mv |
CC-BY-SA |
eu_rights_str_mv |
embargoedAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Programa de Pós-graduação em Química Orgânica Química Orgânica |
publisher.none.fl_str_mv |
Programa de Pós-graduação em Química Orgânica Química Orgânica |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da Universidade Federal Fluminense (RIUFF) instname:Universidade Federal Fluminense (UFF) instacron:UFF |
instname_str |
Universidade Federal Fluminense (UFF) |
instacron_str |
UFF |
institution |
UFF |
reponame_str |
Repositório Institucional da Universidade Federal Fluminense (RIUFF) |
collection |
Repositório Institucional da Universidade Federal Fluminense (RIUFF) |
repository.name.fl_str_mv |
Repositório Institucional da Universidade Federal Fluminense (RIUFF) - Universidade Federal Fluminense (UFF) |
repository.mail.fl_str_mv |
riuff@id.uff.br |
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1811823674764820480 |