5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia
Ano de defesa: | 2007 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | , |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
|
Programa de Pós-Graduação: |
Programa de Pós-Graduação em Química
|
Departamento: |
Química
|
País: |
BR
|
Palavras-chave em Português: | |
Palavras-chave em Inglês: | |
Área do conhecimento CNPq: | |
Link de acesso: | http://repositorio.ufsm.br/handle/1/10638 |
Resumo: | An efficient method to obtain six 4-alkoxy-2-oxo-but-3-enoic acid ethyl esters [EtO2CC(O)C(R2)=C(R1)OR, where R1/R2/R = Me/H/Me (2a), Ph/H/Me (2b), 4-MeC6H4/H/Me (2c), 4-BrC6H4/H/Me (2d), 4-FC6H4/H/Me (2e), H/Me/Et (2f)] from acylation of enol ethers or acetals with ethyl oxalyl chloride is reported. The cyclocondensation reaction of these substrates and their trifluormethylated analogues (5a-f) [CF3C(O)C(R2)=C(OR)R1] with salicylic hydrazide furnished a series of ethyl 5-hydroxy-1-(2-hydroxybenzoyl)-4,5-dihydro-1H-pyrazole-5-carboxylates (6) and 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-(2-hydroxybenzoyl)pyrazoles (7), respectively. The structure of the obtained compounds was determined by spectroscopy and confirmed by crystallographic studies. The design of these compounds explore the hypothesis that the hybridization of salicylic acid with an appropriate 4,5-dihydro-1Hpyrazole scaffold can supply novel potent analgesic agents. The oral administration of one compound of each series of pyrazoles (6a, 7a) caused significant analgesia in the writhing test in mice, which was similar to the analgesia caused by aspirin. |
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2007-11-092007-11-092007-02-23MACHADO, Pablo. 5-hydroxy-4,5-dihydro-1H-1-(2-hydroxybenzoyl)pyrazoles: design, synthesis and analgesia. 2007. 179 f. Dissertação (Mestrado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2007.http://repositorio.ufsm.br/handle/1/10638An efficient method to obtain six 4-alkoxy-2-oxo-but-3-enoic acid ethyl esters [EtO2CC(O)C(R2)=C(R1)OR, where R1/R2/R = Me/H/Me (2a), Ph/H/Me (2b), 4-MeC6H4/H/Me (2c), 4-BrC6H4/H/Me (2d), 4-FC6H4/H/Me (2e), H/Me/Et (2f)] from acylation of enol ethers or acetals with ethyl oxalyl chloride is reported. The cyclocondensation reaction of these substrates and their trifluormethylated analogues (5a-f) [CF3C(O)C(R2)=C(OR)R1] with salicylic hydrazide furnished a series of ethyl 5-hydroxy-1-(2-hydroxybenzoyl)-4,5-dihydro-1H-pyrazole-5-carboxylates (6) and 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-(2-hydroxybenzoyl)pyrazoles (7), respectively. The structure of the obtained compounds was determined by spectroscopy and confirmed by crystallographic studies. The design of these compounds explore the hypothesis that the hybridization of salicylic acid with an appropriate 4,5-dihydro-1Hpyrazole scaffold can supply novel potent analgesic agents. The oral administration of one compound of each series of pyrazoles (6a, 7a) caused significant analgesia in the writhing test in mice, which was similar to the analgesia caused by aspirin.Este trabalho descreve um eficiente método para obter seis 4-alcóxi-2-oxo-3-butenoatos de etila [EtO2CC(O)C(R2)=C(R1)OR, onde R1/R2/R = Me/H/Me (2a), Ph/H/Me (2b), 4-MeC6H4/H/Me (2c), 4-BrC6H4/H/Me (2d), 4-FC6H4/H/Me (2e), H/Me/Et (2f)] a partir da acilação de enoléteres e acetais com cloreto de etil oxalila. A reação de ciclocondensação desses substratos e seus análogos trifluormetilados (5a-f) [CF3C(O)C(R2)=C(OR)R1] com salicil hidrazida forneceu respectivamente as séries de 5-etilcarboxilato-5-hidróxi-4,5-diidro-1H-1-(2-hidroxibenzoil)pirazóis (6) e 5-hidróxi-5-trifluormetil-4,5-diidro-1H-1-(2-hidroxibenzoil)pirazóis (7). Adicionalmente aos dados espectroscópicos, a estrutura dos compostos foi confirmada por experimentos de raios-X. O planejamento desses compostos explora a hipótese de que a hibridização molecular do ácido salicílico com um núcleo 4,5-diidro-1H-pirazol pode fornecer novos potentes agentes analgésicos. A administração oral de um exemplo de cada série de pirazóis (6a, 7a) causou um efeito analgésico significante no teste das contorções abdominais em camundongos, o qual foi similar ao efeito analgésico apresentado pela aspirina.Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em QuímicaUFSMBRQuímicaPirazóisEnonasÁcido salicílicoRaios-XDorPyrazolesEnonesSalicylic acidX-rayPainCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia5-Hydroxy-4,5-Dihydro-1h-1-(2-hydroxybenzoyl)pyrazoles: design, synthesis and analgesiainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisMartins, Marcos Antonio Pintohttp://lattes.cnpq.br/6457412713967642Zanatta, Nilohttp://lattes.cnpq.br/0719465062354576Mello, Carlos Fernando dehttp://lattes.cnpq.br/3913887223894236http://lattes.cnpq.br/3319303431365448Machado, Pablo100600000000400500500500500c28419d9-6027-4f9c-acd2-76e8067a85d183c45c11-ef76-4534-81c7-969c9888cfaa12036c3b-18f6-4b7d-ad7e-5fd56bfce1d7a3555916-7e5c-48ce-8d5c-94f0e1316dd0info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALDIS_PPGQUIMICA_2007_MACHADO_PABLO.pdfDissertação de Mestradoapplication/pdf2879221http://repositorio.ufsm.br/bitstream/1/10638/1/DIS_PPGQUIMICA_2007_MACHADO_PABLO.pdf121b6ec0c0c3961a46c7ebfe60bcc3abMD511/106382022-08-11 15:28:07.918oai:repositorio.ufsm.br:1/10638Repositório Institucionalhttp://repositorio.ufsm.br/PUBhttp://repositorio.ufsm.br/oai/requestopendoar:39132022-08-11T18:28:07Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia |
dc.title.alternative.eng.fl_str_mv |
5-Hydroxy-4,5-Dihydro-1h-1-(2-hydroxybenzoyl)pyrazoles: design, synthesis and analgesia |
title |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia |
spellingShingle |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia Machado, Pablo Pirazóis Enonas Ácido salicílico Raios-X Dor Pyrazoles Enones Salicylic acid X-ray Pain CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia |
title_full |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia |
title_fullStr |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia |
title_full_unstemmed |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia |
title_sort |
5-Hidróxi-4,5-Diidro-1h-1-(2-hidroxibenzoil)pirazóis: planejamento, síntese e analgesia |
author |
Machado, Pablo |
author_facet |
Machado, Pablo |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Martins, Marcos Antonio Pinto |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/6457412713967642 |
dc.contributor.referee1.fl_str_mv |
Zanatta, Nilo |
dc.contributor.referee1Lattes.fl_str_mv |
http://lattes.cnpq.br/0719465062354576 |
dc.contributor.referee2.fl_str_mv |
Mello, Carlos Fernando de |
dc.contributor.referee2Lattes.fl_str_mv |
http://lattes.cnpq.br/3913887223894236 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/3319303431365448 |
dc.contributor.author.fl_str_mv |
Machado, Pablo |
contributor_str_mv |
Martins, Marcos Antonio Pinto Zanatta, Nilo Mello, Carlos Fernando de |
dc.subject.por.fl_str_mv |
Pirazóis Enonas Ácido salicílico Raios-X Dor |
topic |
Pirazóis Enonas Ácido salicílico Raios-X Dor Pyrazoles Enones Salicylic acid X-ray Pain CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Pyrazoles Enones Salicylic acid X-ray Pain |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
An efficient method to obtain six 4-alkoxy-2-oxo-but-3-enoic acid ethyl esters [EtO2CC(O)C(R2)=C(R1)OR, where R1/R2/R = Me/H/Me (2a), Ph/H/Me (2b), 4-MeC6H4/H/Me (2c), 4-BrC6H4/H/Me (2d), 4-FC6H4/H/Me (2e), H/Me/Et (2f)] from acylation of enol ethers or acetals with ethyl oxalyl chloride is reported. The cyclocondensation reaction of these substrates and their trifluormethylated analogues (5a-f) [CF3C(O)C(R2)=C(OR)R1] with salicylic hydrazide furnished a series of ethyl 5-hydroxy-1-(2-hydroxybenzoyl)-4,5-dihydro-1H-pyrazole-5-carboxylates (6) and 5-hydroxy-5-trifluoromethyl-4,5-dihydro-1H-1-(2-hydroxybenzoyl)pyrazoles (7), respectively. The structure of the obtained compounds was determined by spectroscopy and confirmed by crystallographic studies. The design of these compounds explore the hypothesis that the hybridization of salicylic acid with an appropriate 4,5-dihydro-1Hpyrazole scaffold can supply novel potent analgesic agents. The oral administration of one compound of each series of pyrazoles (6a, 7a) caused significant analgesia in the writhing test in mice, which was similar to the analgesia caused by aspirin. |
publishDate |
2007 |
dc.date.accessioned.fl_str_mv |
2007-11-09 |
dc.date.available.fl_str_mv |
2007-11-09 |
dc.date.issued.fl_str_mv |
2007-02-23 |
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.citation.fl_str_mv |
MACHADO, Pablo. 5-hydroxy-4,5-dihydro-1H-1-(2-hydroxybenzoyl)pyrazoles: design, synthesis and analgesia. 2007. 179 f. Dissertação (Mestrado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2007. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/10638 |
identifier_str_mv |
MACHADO, Pablo. 5-hydroxy-4,5-dihydro-1H-1-(2-hydroxybenzoyl)pyrazoles: design, synthesis and analgesia. 2007. 179 f. Dissertação (Mestrado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2007. |
url |
http://repositorio.ufsm.br/handle/1/10638 |
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por |
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100600000000 |
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400 500 500 500 500 |
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Universidade Federal de Santa Maria |
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UFSM |
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BR |
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Química |
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