FVP of 2-methoxy-N-(arenylidene)anilines gave benzoxazoles¡Fboth FVP and photolysis of 2-thiomethoxy-N-(arenylidene)anilines gave benzothiazoles.

No description available.

The first chapter describe the pyrolytic and photolytic studies of substituted styrylarenes. Flash vacuum pyrolysis (FVP) of (2-(4-methoxystyryl)-N-methylindole) (18) gave (4-vinylphenol) (81)¡B (7-methyl-7H-benzo[c]carbazole) (82)¡B (benzo[c]carbazole) (83)¡B (1,6-dihydrocyclopenta[c]carbazole) (84) and (3,6-dihydrocyclopenta- [c]carbazole) (84'). FVP of 2',3,5-trimethoxystilbene (31) gave 2-(3,5-dihydroxyphenyl)benzo[b]furan) (26) and 2-(3,5-dimethoxy- phenyl)benzo[b]furan (95). FVP of 2-methoxy-4-(methoxymethyl)-1- [2-(4-methoxyphenyl)-1-methylvinyl]benzene (33) gave [2-(4- methoxyphenyl)-3-methylbenzofuran-5-yl]methanol (104)¡B4-(3,5- dimethylbenzofuran-2-yl)phenol (105) and 2-(4-hydroxyphenyl)-3- methylbenzofuran-5-carbaldehyde (106). FVP of 2-(2-chlorostyryl)- benzo[b]furan (44) ¡B2-(2-chlorostyryl)benzo[b]thiophene (45) and 2-(2-chlorostyryl)-N-methylindole (46) gave benzo[b]naphtha[1,2-d]- furan (116)¡Bbenzo[b]naphtho[1,2-d]thiophene (117)¡B7-methyl-7H- benzo[c] carbazole (82) and benzo[c]carbazole (83). FVP of 2-chloro-N-(N-methylindol-2-ylmethylene)aniline (71) gave N-methylindole-2-carbonitrile (124)¡B 7H-indolo[2,3-c]quinoline (125) and indolo[1,2-a]quinoxaline (126). FVP of 2-methoxy -N-(N-methyl- indol-2-ylmethylene)aniline (72) gave N-methylindole-2-carbonitrile (124) ¡B 2-(N-methylindol- 2-yl)benzoxazole (132) and 2-hydroxy- benzonitrile (133). FVP of 2-methylthio-N-(phenylmethylene)aniline (73)¡B2-methylthio-N-(furylmethylene)aniline (74)¡B2-methylthio-N- (benzo[b]thiophen-2-ylmethylene)aniline (75) and 2-methylthio-N- (N-methylindol-2-ylmethylene)aniline (76) gave 2-phenylbenzothiazole (143)¡B2-furylbenzothiazole (144)¡B2-benzo[b]thiophen-2-ylbenzo- thiazole (145)¡B2-(N-methylindol-2-yl)benzothiazole (146)¡B2-(1H- indol-2-yl)benzothiazole (147) and benzothiazole (148).Such a method, via oxygen-carbon bond disconnecting, can synthesize efficiently a nature product, stemofuran A 26. Photolytic study of 2',3,5-trimethoxystilbene (31) gave 1,5,7- trimethoxyphenanthrene) (101). Photolytic studies of 2-(2-chloro- styryl)benzo[b]furan (44) ¡B2-(2-chlorostyryl)benzo[b]thiophene (45) and 2-(2-chlorostyryl)-N-methylindole (46) gave benzo[b]naphtha- [1,2-d]furan (116) and 4-chlorobenzo[b]naphtha[1,2-d]furan (120)¡Bbenzo[b]naphtho[1,2-d]thiophene (117) and 4-chlorobenzo[b]naphtha- [1,2-d]thiophene (120) ¡B7-methyl-7H- benzo[c]carbazole (82) and 4-chloro-7-methyl-7H-benzo[c]carbazole (121). Photolytic studies of 2-methylthio-N-(phenylmethylene)aniline (73)¡B2-methylthio- -N-(furylmethylene)aniline (74)¡B2-methylthio-N-(benzo[b]thiophen-2- ylmethylene)aniline (75) and 2-methylthio-N-(N-methylindol-2- ylmethylene)aniline (76) gave 2-phenylbenzothiazole (143)¡B2-furyl- benzothiazole (144)¡B2-benzo[b]thiophen-2-ylbenzo- thiazole (145)¡B2-(N-methylindol-2-yl)benzothiazole (146)¡B2-(1H-indol-2-yl)benzo- thiazole (147) and 2-(2,4-dimethoxyphenyl)benzothiazole) (60f). Such a method has the potential for preparing drugs and application on material science. (¤G)FVP of 2-inden-1-ylidenemethylthiophene (24) and 2-inden-1-ylidene- methylfuran (25) gave the cyclized products 2-(2'-thienyl)naphthalene (29) and 2-(2'-furyl)naphthalene (32).

Este trabalho apresenta a síntese, caracterização e estudo fotofísico de novos heterociclos benzazólicos fluorescentes com potencial aplicação como sondas de ambientes lipídicos. Para isso, foram sintetizados três corantes que contêm em sua estrutura cadeias alquílicas de oito, doze e dezoito átomos de carbono ligados a um núcleo benzazólico que é o responsável pela fluorescência destes compostos. O corante que possui a cadeia alquílica de dezoito carbonos apresenta-se ainda na forma de um sal de amônio quaternário, com o objetivo de tornar a sua estrutura mais anfifílica do que os seus análogos neutros de oito e doze carbonos, e com isso, promover a interação entre meios que apresentam polaridade diferente como, por exemplo, água e membrana. A obtenção dos derivados contendo oito e doze carbonos foi realizada a partir da reação de substituição nucleofílica entre o heterociclo 2-(5’-amino-2’-hidroxifenil)benzoxazol e os respectivos iodoalcanos em presença de uma base, com rendimentos na faixa de 45%. O derivado com dezoito carbonos foi obtido em duas etapas, sendo a primeira a reação entre o 2- (5’-amino-2’-hidroxifenil)benzoxazol e a epicloridrina para formar o intermediário 2-(5’(N-3- cloro-2-hidroxipropilamina)-2’-hidroxifenil)benzoxazol. A reação deste intermediário com a N,N-dimetiloctadecilamina levou a formação do corante na forma de sal de amônio quaternário com 68% de rendimento. Os corantes foram caracterizados por Infravermelho, Ressonância Magnética Nuclear de Hidrogênio e de Carbono, Análise Elementar e ponto de fusão, além da caracterização fotofísica. O estudo fotofísico do sistema fosfatidilcolina/corante mostrou que os corantes sofrem a influência do meio lipídico, bem como a afinidade do corante quaternizado pelo sistema lipídico diferencia-se dos corantes neutros. Além disso, os corantes com cadeias alquílicas de oito e doze átomos de carbono se mostraram sondas mais eficientes para meios apolares ou polares apróticos e são liberados para o meio com o aumento da diluição do sistema. Já o corante com cadeia alquílica de dezoito átomos de carbono apresentou maior afinidade com o ambiente hidrofílico do sistema lipídico, ficando incorporado na bicamada lipídica, mesmo com o aumento da diluição. / This work presents the synthesis, characterization and photophysical study of new fluorescent benzazólicos heterocycles with potential application as probes of lipid environments. For this, three dyes were synthesized containing alkyl chains in the structure of eight, twelve and eighteen carbon atoms attached to a core benzazólico which is responsible for the fluorescence of these compounds. The dye that has the alkyl chain of eighteen carbons still presents as a quaternary ammonium salt, with the goal of making its structure more amphiphilic than their neutral analogues of eight and twelve carbons, and thereby promote the interaction means that present different polarity, for example, water and membrane. The obtaining of derivatives containing eight twelve carbons was made from the nucleophilic substitution reaction between the heterocycle 2-(5'-amino-2'-hydroxyphenyl) benzoxazole and its iodoalcanos in the presence of a base, with yields around 45%. The derivative eighteen carbons was obtained in two steps, the first being the reaction between 2- (5'-amino-2'-hydroxyphenyl) benzoxazole and epichlorohydrin to form the intermediate 2- (5'(N-3-chloro-2-hydroxypropylamine)-2'-hydroxyphenyl) benzoxazole. The reaction of this intermediate with N, N-dimetiloctadecilamina led to the formation of the desired compound quaternised 68% yield. The compounds were characterized by infrared, nuclear magnetic resonance of hydrogen and carbon, elemental analysis and melting point, besides the characterization photophysics. The photophysical study of the phosphatidylcholine/dye system showed that the dyes suffer the influence of the lipid and affinity of the dye quaternized by the system differs from dyes that show no load. In addition, the neutral dyes with alkyl chains content eight and twelve carbon atoms, proved most interesting probes for apolar media or polar aprotic media and are released into the medium with increasing dilution of the system. Already the derivative with eighteen carbon atoms and having quaternary nitrogen showed higher affinity for hydrophilic environment lipid system, becoming incorporated into the lipid bilayer, even with increased dilution.

Este trabalho apresenta a síntese, caracterização e estudo fotofísico de novos heterociclos benzazólicos fluorescentes com potencial aplicação como sondas de ambientes lipídicos. Para isso, foram sintetizados três corantes que contêm em sua estrutura cadeias alquílicas de oito, doze e dezoito átomos de carbono ligados a um núcleo benzazólico que é o responsável pela fluorescência destes compostos. O corante que possui a cadeia alquílica de dezoito carbonos apresenta-se ainda na forma de um sal de amônio quaternário, com o objetivo de tornar a sua estrutura mais anfifílica do que os seus análogos neutros de oito e doze carbonos, e com isso, promover a interação entre meios que apresentam polaridade diferente como, por exemplo, água e membrana. A obtenção dos derivados contendo oito e doze carbonos foi realizada a partir da reação de substituição nucleofílica entre o heterociclo 2-(5’-amino-2’-hidroxifenil)benzoxazol e os respectivos iodoalcanos em presença de uma base, com rendimentos na faixa de 45%. O derivado com dezoito carbonos foi obtido em duas etapas, sendo a primeira a reação entre o 2- (5’-amino-2’-hidroxifenil)benzoxazol e a epicloridrina para formar o intermediário 2-(5’(N-3- cloro-2-hidroxipropilamina)-2’-hidroxifenil)benzoxazol. A reação deste intermediário com a N,N-dimetiloctadecilamina levou a formação do corante na forma de sal de amônio quaternário com 68% de rendimento. Os corantes foram caracterizados por Infravermelho, Ressonância Magnética Nuclear de Hidrogênio e de Carbono, Análise Elementar e ponto de fusão, além da caracterização fotofísica. O estudo fotofísico do sistema fosfatidilcolina/corante mostrou que os corantes sofrem a influência do meio lipídico, bem como a afinidade do corante quaternizado pelo sistema lipídico diferencia-se dos corantes neutros. Além disso, os corantes com cadeias alquílicas de oito e doze átomos de carbono se mostraram sondas mais eficientes para meios apolares ou polares apróticos e são liberados para o meio com o aumento da diluição do sistema. Já o corante com cadeia alquílica de dezoito átomos de carbono apresentou maior afinidade com o ambiente hidrofílico do sistema lipídico, ficando incorporado na bicamada lipídica, mesmo com o aumento da diluição. / This work presents the synthesis, characterization and photophysical study of new fluorescent benzazólicos heterocycles with potential application as probes of lipid environments. For this, three dyes were synthesized containing alkyl chains in the structure of eight, twelve and eighteen carbon atoms attached to a core benzazólico which is responsible for the fluorescence of these compounds. The dye that has the alkyl chain of eighteen carbons still presents as a quaternary ammonium salt, with the goal of making its structure more amphiphilic than their neutral analogues of eight and twelve carbons, and thereby promote the interaction means that present different polarity, for example, water and membrane. The obtaining of derivatives containing eight twelve carbons was made from the nucleophilic substitution reaction between the heterocycle 2-(5'-amino-2'-hydroxyphenyl) benzoxazole and its iodoalcanos in the presence of a base, with yields around 45%. The derivative eighteen carbons was obtained in two steps, the first being the reaction between 2- (5'-amino-2'-hydroxyphenyl) benzoxazole and epichlorohydrin to form the intermediate 2- (5'(N-3-chloro-2-hydroxypropylamine)-2'-hydroxyphenyl) benzoxazole. The reaction of this intermediate with N, N-dimetiloctadecilamina led to the formation of the desired compound quaternised 68% yield. The compounds were characterized by infrared, nuclear magnetic resonance of hydrogen and carbon, elemental analysis and melting point, besides the characterization photophysics. The photophysical study of the phosphatidylcholine/dye system showed that the dyes suffer the influence of the lipid and affinity of the dye quaternized by the system differs from dyes that show no load. In addition, the neutral dyes with alkyl chains content eight and twelve carbon atoms, proved most interesting probes for apolar media or polar aprotic media and are released into the medium with increasing dilution of the system. Already the derivative with eighteen carbon atoms and having quaternary nitrogen showed higher affinity for hydrophilic environment lipid system, becoming incorporated into the lipid bilayer, even with increased dilution.

Este trabalho apresenta a síntese, caracterização e estudo fotofísico de novos heterociclos benzazólicos fluorescentes com potencial aplicação como sondas de ambientes lipídicos. Para isso, foram sintetizados três corantes que contêm em sua estrutura cadeias alquílicas de oito, doze e dezoito átomos de carbono ligados a um núcleo benzazólico que é o responsável pela fluorescência destes compostos. O corante que possui a cadeia alquílica de dezoito carbonos apresenta-se ainda na forma de um sal de amônio quaternário, com o objetivo de tornar a sua estrutura mais anfifílica do que os seus análogos neutros de oito e doze carbonos, e com isso, promover a interação entre meios que apresentam polaridade diferente como, por exemplo, água e membrana. A obtenção dos derivados contendo oito e doze carbonos foi realizada a partir da reação de substituição nucleofílica entre o heterociclo 2-(5’-amino-2’-hidroxifenil)benzoxazol e os respectivos iodoalcanos em presença de uma base, com rendimentos na faixa de 45%. O derivado com dezoito carbonos foi obtido em duas etapas, sendo a primeira a reação entre o 2- (5’-amino-2’-hidroxifenil)benzoxazol e a epicloridrina para formar o intermediário 2-(5’(N-3- cloro-2-hidroxipropilamina)-2’-hidroxifenil)benzoxazol. A reação deste intermediário com a N,N-dimetiloctadecilamina levou a formação do corante na forma de sal de amônio quaternário com 68% de rendimento. Os corantes foram caracterizados por Infravermelho, Ressonância Magnética Nuclear de Hidrogênio e de Carbono, Análise Elementar e ponto de fusão, além da caracterização fotofísica. O estudo fotofísico do sistema fosfatidilcolina/corante mostrou que os corantes sofrem a influência do meio lipídico, bem como a afinidade do corante quaternizado pelo sistema lipídico diferencia-se dos corantes neutros. Além disso, os corantes com cadeias alquílicas de oito e doze átomos de carbono se mostraram sondas mais eficientes para meios apolares ou polares apróticos e são liberados para o meio com o aumento da diluição do sistema. Já o corante com cadeia alquílica de dezoito átomos de carbono apresentou maior afinidade com o ambiente hidrofílico do sistema lipídico, ficando incorporado na bicamada lipídica, mesmo com o aumento da diluição. / This work presents the synthesis, characterization and photophysical study of new fluorescent benzazólicos heterocycles with potential application as probes of lipid environments. For this, three dyes were synthesized containing alkyl chains in the structure of eight, twelve and eighteen carbon atoms attached to a core benzazólico which is responsible for the fluorescence of these compounds. The dye that has the alkyl chain of eighteen carbons still presents as a quaternary ammonium salt, with the goal of making its structure more amphiphilic than their neutral analogues of eight and twelve carbons, and thereby promote the interaction means that present different polarity, for example, water and membrane. The obtaining of derivatives containing eight twelve carbons was made from the nucleophilic substitution reaction between the heterocycle 2-(5'-amino-2'-hydroxyphenyl) benzoxazole and its iodoalcanos in the presence of a base, with yields around 45%. The derivative eighteen carbons was obtained in two steps, the first being the reaction between 2- (5'-amino-2'-hydroxyphenyl) benzoxazole and epichlorohydrin to form the intermediate 2- (5'(N-3-chloro-2-hydroxypropylamine)-2'-hydroxyphenyl) benzoxazole. The reaction of this intermediate with N, N-dimetiloctadecilamina led to the formation of the desired compound quaternised 68% yield. The compounds were characterized by infrared, nuclear magnetic resonance of hydrogen and carbon, elemental analysis and melting point, besides the characterization photophysics. The photophysical study of the phosphatidylcholine/dye system showed that the dyes suffer the influence of the lipid and affinity of the dye quaternized by the system differs from dyes that show no load. In addition, the neutral dyes with alkyl chains content eight and twelve carbon atoms, proved most interesting probes for apolar media or polar aprotic media and are released into the medium with increasing dilution of the system. Already the derivative with eighteen carbon atoms and having quaternary nitrogen showed higher affinity for hydrophilic environment lipid system, becoming incorporated into the lipid bilayer, even with increased dilution.

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No description available.

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La maladie d’Alzheimer (MA) est la maladie neurodégénérative touchant le plus de personnes dans le monde. Jusqu’à présent, aucun traitement curatif n’existe pour soigner cette maladie, d’où la nécessité d’identifier et d’étudier de nouvelles cibles thérapeutiques.La découverte des effets bénéfiques de la caféine, antagoniste du récepteur à adénosine A2A (A2AR), conjuguée à une surexpression de ce dernier chez les patients atteints de la MA, font de ce récepteur une cible d’intérêt. En effet, des antagonistes des A2ARs ont montré leur capacité à améliorer les performances cognitives de par une diminution de la charge amyloïde associée à une diminution la phosphorylation de la protéine Tau.Bien que plusieurs antagonistes aient été développés pour le traitement de maladies neurodégénératives, ceux-ci présentent un manque d’efficacité corrélée à de faibles propriétés pharmacocinétiques. Ainsi, à partir d’études de modélisation moléculaire, deux nouvelles familles d’antagonistes présentant un noyau central benzoxazole ou quinazoline ont été conçus, synthétisés et évalués pharmacologiquement. Trois composés ont été sélectionnés et font actuellement l’objet d’études pharmacologiques complémentaires sur modèles animaux. / Alzheimer’s disease (AD) is the most prevalent form of dementia in the aged population. So far, there is no way to halt or slow-down AD. Therefore, there is a constant need of developing novel therapeutic strategies.In recent years, adenosine A2A receptor (A2AR) has attracted a growing interest since it has been proved that this receptor is over-expressed during AD. Also, epidemiological studies showed that people consuming regularly caffeine-based beverages over a lifetime are substantially less likely to develop this disease. Indeed, A2AR antagonists improve memory performance as it reduces β-amyloid deposits and Tau-phosphorylation.Though several antagonists have been developed for the treatment of neurodegenerative diseases, current research efforts are focus on developing new antagonists with relevant ADME properties and a better efficacy. Based on a molecular modeling-guided design, we synthesised new A2AR antagonists with benzoxazole and quinazoline as central scaffold. Three molecules were selected and will be subject to evaluation on animal’s model.