Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico
Ano de defesa: | 2016 |
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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/1/10627 |
Resumo: | A convergent synthesis of a series of 16 new polysubstituted (5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-4-yl)methanones, starting from isatin and alky(aryl/heteroaryl) ketones, is described. The diheteroaryl methanones were achieved at yields of up to 95% by a (3 + 2) cyclocondensation reaction involving 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (by two-step reaction) and 2-alkyl(aryl/heteroaryl)-4-carbohydrazides (by three-step reaction). Subsequently, representative dehydrated heterocyclic derivatives were obtained from the respective 5-hydroxy-2-pyrazoline moieties by classical dehydration reactions, which resulted in the corresponding (5-(trifluoromethyl)-1H-pyrazol-1-yl)(quinolin-4-yl)methanones (three examples) at yields of 69 82%. The compounds were characterized by one- and two-dimensional 1H/13C NMR, X-ray diffraction, GC-MS and elemental analysis. The subsequent cytotoxicity evaluation showed that compounds with aromatic groups at the 2-position of the quinoline and a methyl moiety at the 3-position of the pyrazole have significant cytotoxicity in human leukocytes at high concentrations (200 μM). |
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2017-05-192017-05-192016-07-22NOGARA, Pablo Andrei. Synthesis of (5-trifluoromethyl-1H-pyrazol-1-YL)(quinolin-4-YL)methanones of pharmacological interest. 2016. 132 f. Dissertação (Mestrado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2016.http://repositorio.ufsm.br/handle/1/10627A convergent synthesis of a series of 16 new polysubstituted (5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-4-yl)methanones, starting from isatin and alky(aryl/heteroaryl) ketones, is described. The diheteroaryl methanones were achieved at yields of up to 95% by a (3 + 2) cyclocondensation reaction involving 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (by two-step reaction) and 2-alkyl(aryl/heteroaryl)-4-carbohydrazides (by three-step reaction). Subsequently, representative dehydrated heterocyclic derivatives were obtained from the respective 5-hydroxy-2-pyrazoline moieties by classical dehydration reactions, which resulted in the corresponding (5-(trifluoromethyl)-1H-pyrazol-1-yl)(quinolin-4-yl)methanones (three examples) at yields of 69 82%. The compounds were characterized by one- and two-dimensional 1H/13C NMR, X-ray diffraction, GC-MS and elemental analysis. The subsequent cytotoxicity evaluation showed that compounds with aromatic groups at the 2-position of the quinoline and a methyl moiety at the 3-position of the pyrazole have significant cytotoxicity in human leukocytes at high concentrations (200 μM).Uma síntese convergente de uma série de 16 novos poli-substituídos (5-hidroxi-5-(trifluorometil)-4,5-di-hidro-1H-pirazol-1-il)(quinolin-4-il)metanonas, a partir da isatina e alquil(aril/heteroaril)cetonas, é descrito. As diheteroarilmetanonas foram obtidas com rendimentos de até 95% por uma reação de ciclocondensação (3 + 2) envolvendo 4-alquil(aril/heteroaril)-4-metóxi-1,1,1-trifluorbut-3-en-2-onas (reação em dois passos) e 2-alquil(aril/heteroaril)-4-carbohidrazidas (reação em três passos). Subsequentemente, os representantes desidratados dos heterociclos foram obtidos a partir das respectivas porções de 5-hidróxi-2-pirazolina por reações de desidratação clássicas, o que resultou nas correspondentes (5-(trifluormetil)-1H-pirazol-1-il)(quinolin-4-il )metanonas (três exemplos) com rendimentos de 69-82%. Os compostos foram caracterizados por RMN de 1H e 13C uni e bidimensional, difração de raios-X, CG-EM e análise elementar. As posteriores avaliações da citotoxicidade mostraram que os compostos com grupos aromáticos na posição 2 da quinolina e o grupo metila na posição 3 do pirazol, possuem significativa citotoxicidade em leucócitos humanos em concentrações elevadas (200 μM).Coordenação de Aperfeiçoamento de Pessoal de Nível Superiorapplication/pdfporUniversidade Federal de Santa MariaPrograma de Pós-Graduação em QuímicaUFSMBRQuímicaQuinolinasPirazóisCetonasHidrazidasAvaliação da citotoxicidadeQuinolinesPyrazolesKetonesHydrazidesCytotoxicity evaluationCNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICASíntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológicoSynthesis of (5-trifluoromethyl-1H-pyrazol-1-YL)(quinolin-4-YL)methanones of pharmacological interestinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisBonacorso, Helio Gauzehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788537E0Mostardeiro, Marco Aureliohttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785681E6Costa, Michelle Budkehttp://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4739018Y3http://lattes.cnpq.br/8323436856891273Nogara, Pablo Andrei10060000000040050030050030006c852ad-d805-43c3-99d6-93a6a86f507c1b7f098d-470e-4587-8a7f-d6dc3b3e29cc6190e59b-afb1-46bf-8172-0091c1964025244ee975-1b0f-4c57-b99d-009b75caf0afinfo:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMORIGINALNOGARA, PABLO ANDREI.pdfapplication/pdf9371671http://repositorio.ufsm.br/bitstream/1/10627/1/NOGARA%2c%20PABLO%20ANDREI.pdf79896ca694590063cabe95e4b5e3d864MD51TEXTNOGARA, PABLO ANDREI.pdf.txtNOGARA, PABLO ANDREI.pdf.txtExtracted texttext/plain168422http://repositorio.ufsm.br/bitstream/1/10627/2/NOGARA%2c%20PABLO%20ANDREI.pdf.txtabd662b54f597449f6adac1304415419MD52THUMBNAILNOGARA, PABLO ANDREI.pdf.jpgNOGARA, PABLO ANDREI.pdf.jpgIM Thumbnailimage/jpeg4127http://repositorio.ufsm.br/bitstream/1/10627/3/NOGARA%2c%20PABLO%20ANDREI.pdf.jpg9315d7c4f0d41ab221431d1e44871f15MD531/106272017-07-25 12:05:10.979oai:repositorio.ufsm.br:1/10627Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2017-07-25T15:05:10Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.por.fl_str_mv |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico |
dc.title.alternative.eng.fl_str_mv |
Synthesis of (5-trifluoromethyl-1H-pyrazol-1-YL)(quinolin-4-YL)methanones of pharmacological interest |
title |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico |
spellingShingle |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico Nogara, Pablo Andrei Quinolinas Pirazóis Cetonas Hidrazidas Avaliação da citotoxicidade Quinolines Pyrazoles Ketones Hydrazides Cytotoxicity evaluation CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
title_short |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico |
title_full |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico |
title_fullStr |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico |
title_full_unstemmed |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico |
title_sort |
Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico |
author |
Nogara, Pablo Andrei |
author_facet |
Nogara, Pablo Andrei |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Bonacorso, Helio Gauze |
dc.contributor.advisor1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4788537E0 |
dc.contributor.referee1.fl_str_mv |
Mostardeiro, Marco Aurelio |
dc.contributor.referee1Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4785681E6 |
dc.contributor.referee2.fl_str_mv |
Costa, Michelle Budke |
dc.contributor.referee2Lattes.fl_str_mv |
http://buscatextual.cnpq.br/buscatextual/visualizacv.do?id=K4739018Y3 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8323436856891273 |
dc.contributor.author.fl_str_mv |
Nogara, Pablo Andrei |
contributor_str_mv |
Bonacorso, Helio Gauze Mostardeiro, Marco Aurelio Costa, Michelle Budke |
dc.subject.por.fl_str_mv |
Quinolinas Pirazóis Cetonas Hidrazidas Avaliação da citotoxicidade |
topic |
Quinolinas Pirazóis Cetonas Hidrazidas Avaliação da citotoxicidade Quinolines Pyrazoles Ketones Hydrazides Cytotoxicity evaluation CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
dc.subject.eng.fl_str_mv |
Quinolines Pyrazoles Ketones Hydrazides Cytotoxicity evaluation |
dc.subject.cnpq.fl_str_mv |
CNPQ::CIENCIAS EXATAS E DA TERRA::QUIMICA |
description |
A convergent synthesis of a series of 16 new polysubstituted (5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-4-yl)methanones, starting from isatin and alky(aryl/heteroaryl) ketones, is described. The diheteroaryl methanones were achieved at yields of up to 95% by a (3 + 2) cyclocondensation reaction involving 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (by two-step reaction) and 2-alkyl(aryl/heteroaryl)-4-carbohydrazides (by three-step reaction). Subsequently, representative dehydrated heterocyclic derivatives were obtained from the respective 5-hydroxy-2-pyrazoline moieties by classical dehydration reactions, which resulted in the corresponding (5-(trifluoromethyl)-1H-pyrazol-1-yl)(quinolin-4-yl)methanones (three examples) at yields of 69 82%. The compounds were characterized by one- and two-dimensional 1H/13C NMR, X-ray diffraction, GC-MS and elemental analysis. The subsequent cytotoxicity evaluation showed that compounds with aromatic groups at the 2-position of the quinoline and a methyl moiety at the 3-position of the pyrazole have significant cytotoxicity in human leukocytes at high concentrations (200 μM). |
publishDate |
2016 |
dc.date.issued.fl_str_mv |
2016-07-22 |
dc.date.accessioned.fl_str_mv |
2017-05-19 |
dc.date.available.fl_str_mv |
2017-05-19 |
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 |
NOGARA, Pablo Andrei. Synthesis of (5-trifluoromethyl-1H-pyrazol-1-YL)(quinolin-4-YL)methanones of pharmacological interest. 2016. 132 f. Dissertação (Mestrado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2016. |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/10627 |
identifier_str_mv |
NOGARA, Pablo Andrei. Synthesis of (5-trifluoromethyl-1H-pyrazol-1-YL)(quinolin-4-YL)methanones of pharmacological interest. 2016. 132 f. Dissertação (Mestrado em Química) - Universidade Federal de Santa Maria, Santa Maria, 2016. |
url |
http://repositorio.ufsm.br/handle/1/10627 |
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por |
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100600000000 |
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openAccess |
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Universidade Federal de Santa Maria |
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UFSM |
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Química |
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Universidade Federal de Santa Maria |
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