Submitted by Renata Lopes (renatasil82@gmail.com) on 2016-04-12T18:36:46Z No. of bitstreams: 1 rafaelcarvalhaesmachado.pdf: 15330554 bytes, checksum: b28797a7ed7a97cc333b801efe362c9b (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2016-04-24T03:30:09Z (GMT) No. of bitstreams: 1 rafaelcarvalhaesmachado.pdf: 15330554 bytes, checksum: b28797a7ed7a97cc333b801efe362c9b (MD5) / Made available in DSpace on 2016-04-24T03:30:09Z (GMT). No. of bitstreams: 1 rafaelcarvalhaesmachado.pdf: 15330554 bytes, checksum: b28797a7ed7a97cc333b801efe362c9b (MD5) Previous issue date: 2016-01-22 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / A presente tese, intitulada "Síntese, caracterização e avaliações biológicas de 4-piridinil, 7-cloro-4-quinolinil e 9-acridinil, semicarbazidas e tiossemicarbazidas" descreve a preparação, caracterização e avaliação do potencial biológico de compostos sintéticos híbridos contendo uma porção heterocíclica (núcleo piridínico, quinolínico ou acridínico) associada a uma subunidade tiossemicarbazida ou semicarbazida N-4 substituída. Os compostos almejados foram preparados por duas rotas sintéticas distintas: 1) via reação de substituição nucleofílica aromática entre os derivados halo-heterocíclicos (4-cloropiridina, 4,7-dicloroquinolina e 9-cloroacridina) e as tiossemicarbazidas e semicarbazidas N-4 substituídas e 2) via reação de adição dos derivados heterocíclicos de hidrazina (4-hidrazinopiridina, 7-cloro-4-hidrazinoquinolina e 9-hidrazinoacridina) aos isotiocianatos e isocianatos. As estruturas químicas dos produtos obtidos, bem como as dos intermediários sintéticos, foram caracterizadas por faixa de fusão, espectroscopia no infravermelho, de ressonância magnética nuclear de hidrogênio e de carbono-13 e por espectrometria de massas. Os compostos sintetizados foram avaliados como potenciais agentes antibacterianos (S. aureus, E. coli, P. aeruginosa e S. typhimurium), antituberculares (M. tuberculosis) e antitumorais. Enquanto alguns dos compostos avaliados apresentaram atividade antibacteriana promissora, nenhum dos compostos sintéticos pode ser considerado candidato a agente anti-TB. Em relação a atividade antitumoral, a maioria dos compostos avaliados exibiu elevada citotoxicidade. / The present thesis, entitled “Synthesis, characterization and biological evaluation of 4-pyridinyl, 7-chloro-4-quinolinyl, 9-acridinyl, semicarbazides and thiossemicarbazides”, describes the preparation, characterization and evaluation of the biological potential of synthetic hybrid compounds containing a heterocyclic moiety (pyridine, quinoline or acridine ring) associated with an N-4 substituted semicarbazide or thiosemicarbazide subunit. The desired compounds were prepared by two different synthetic routes: 1) via nucleophilic aromatic substitution reaction between the halo-heterocyclic derivatives (4-chloropyridine, 4,7-dichloroquinoline and 9-chloroacridine) and N-4 substituted thiosemicarbazides and semicarbazides and 2) via addition reaction of the heterocyclic hydrazine derivatives (4-hydrazinopyridine, 7-chloro-4-hydrazinoquinoline and 9-hydrazinoacridine) to isothiocyanates and isocyanates. The chemical structures of the products obtained, as well as synthetic intermediates, were characterized by their melting points, infrared spectroscopy, 1H and 13C nuclear magnetic resonance spectroscopies and by mass spectrometry. The compounds synthesized were evaluated as potential antibacterial (S. aureus, E. coli, P. aeruginosa e S. typhimurium), antituberculosis (M. tuberculosis) and antitumor agents. While some of the evaluated compounds showed promising antibacterial activity, none of the compounds synthesized may be considered a candidate as an anti-TB agent. With respect to antitumor activity, the majority of the evaluated compounds exhibited high cytotoxicity.

Submitted by Geandra Rodrigues (geandrar@gmail.com) on 2018-04-10T18:23:45Z No. of bitstreams: 1 stephanelimacalixto.pdf: 3753314 bytes, checksum: 81fe7e710d2a4f72d60b8c74e25040de (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2018-04-11T15:17:14Z (GMT) No. of bitstreams: 1 stephanelimacalixto.pdf: 3753314 bytes, checksum: 81fe7e710d2a4f72d60b8c74e25040de (MD5) / Made available in DSpace on 2018-04-11T15:17:14Z (GMT). No. of bitstreams: 1 stephanelimacalixto.pdf: 3753314 bytes, checksum: 81fe7e710d2a4f72d60b8c74e25040de (MD5) Previous issue date: 2018-02-22 / As leishmanioses são doenças infecciosas, porém não contagiosas, causadas por protozoários do gênero Leishmania. Os fármacos atualmente empregados para o tratamento das leishmanioses apresentam inúmeros problemas, como alta toxicidade, são dispendiosos, além de mostrarem baixa eficácia em áreas endêmicas devido à resistência observada de várias espécies do parasito. Visto derivados de quinolinas apresentarem como uma classe de moléculas promissoras para o tratamento das leishmanioses, este trabalho teve como objetivo analisar o efeito antileishmanial de novos derivados 4-amino-7-cloroquinolina e a toxicidade em macrófagos peritoneais de camundongos. Objetivou-se também avaliar o modo de ação do composto mais efetivo. Dentre os três compostos avaliados, genericamente denominados de derivados de quinolina (DQ), o composto mais promissor foi o DQ3 (CI50 de 43,25 e 39,19 μM para promastigotas de L. amazonensis e L. braziliensis, respectivamente; CC50 de 226,79 μM; e CI50 de 5,62 e 5,48 para amastigotas de L. amazonensis PH8 e GFP, respectivamente), sendo então o escolhido para os estudos dos possíveis mecanismos de morte celular. Promastigotas de L. amazonensis foram tratados com o composto DQ3 e posteriormente as células foram analisadas quanto a vários parâmetros morfológicos, ultraestruturais e bioquímicos. O tratamento dos promastigotas com o composto DQ3 induziu redução do potencial de membrana mitocondrial, observado pelas marcações com JC-1 e rodamina 123, inchaço mitocondrial observado pela MET e aumento da produção de ROS (marcação com H2DCDFA), sugerindo que o composto tem a mitocôndria como um alvo importante. Além disso, induziu externalização de fosfatidilserina (marcação com anexina V), aumento na população de células na fase sub G0/G1, indução de núcleo apoptótico e alterações morfológicas (corpos arredondados e redução do volume celular). Esses dados sugerem que o composto possa induzir apoptose-like em L. amazonensis. Descartou-se a hipótese de morte por necrose e autofagia, visto que a membrana plasmática se manteve íntegra e não foi observado, pela marcação com MDC, a formação de vacúolos autofágicos. O tratamento dos macrófagos infectados com L. amazonensis induziu aumento na produção de ROS, entretanto o mesmo não foi observado em macrófagos não infectados, sugerindo o estresse oxidativo como um modo de ação deste composto. Também, o tratamento induziu alterações morfológicas nos amastigotas intracelulares. Os resultados obtidos, in vitro, mostram que o composto DQ3 apresenta potencial para ser um agente antileishmanial, estimulando a continuidade da pesquisa no modelo in vivo. / Leishmaniasis is an infectious but non-contagious disease caused by protozoa of the genus Leishmania. The drugs currently used for the treatment of leishmaniasis present numerous problems, such as high toxicity, are expensive, and show low efficacy in endemic areas due to the observed resistance of several species of the parasite. Given quinolines derivatives as a class of promising molecules for the treatment of leishmaniasis, this work aimed to analyze the antileishmanial effect of new 4-amino-7-chloroquinoline derivatives and the toxicity in mouse peritoneal macrophages. The objective of this study was also to evaluate the mode of action of the most effective compound. Among the three evaluated compounds, generically denominated quinoline derivatives (DQ), the most promising compound was DQ3 (IC50 of 43.25 and 39.19 μM for L. amazonensis and L. braziliensis promastigotes, respectively, CC50 of 226.79 μM, and IC50 of 5.62 and 5.48 for amastigotes of L. amazonensis PH8 and GFP, respectively), being then chosen for the studies of the possible mechanisms of cell death. Promastigotes of L. amazonensis were treated with the compound DQ3 and later the cells were analyzed for several morphological, ultrastructural and biochemical parameters. Treatment of the promastigotes with the DQ3 compound induced reduction of the mitochondrial membrane potential observed by the JC-1 and rhodamine-123 markers, mitochondrial swelling observed by MET and increased ROS production (H2DCDFA labeling), suggesting that the compound has the mitochondria as an important target. In addition, it induced phosphatidylserine externalization (annexin V labeling), increase in cell population in the sub G0/G1 phase, induction of apoptotic nucleus and morphological changes (rounded bodies and reduction of cell volume). These data suggest that the compound may induce apoptosis-like in L. amazonensis. The hypothesis of death due to necrosis and autophagy was discarded, since the plasma membrane remained intact and the formation of autophagic vacuoles was not observed by MDC labeling. The treatment of macrophages infected with L. amazonensis induced an increase in the production of ROS, but the same was not observed in uninfected macrophages, suggesting oxidative stress as a mode of action of this compound. Also, the treatment induced morphological changes in intracellular amastigotes. The results obtained, in vitro, show that the compound DQ3 presents potential to be an antileishmanial agent, stimulating the continuity of the research in the in vivo model.

La chimie des hétérocycles est un des domaines les plus importants en chimie organique. En effet, 65% de la littérature en chimie organique traite des hétérocycles. Ils sont largement présents dans la nature, essentiels à la vie et leurs applications sont infinies. Parmi eux, les structures dites privilégiées, attirent une attention particulière. Ces structures privilégiées, dont font partie les quinoléines et les indoles, jouent un rôle central dans la chimie médicinale, pour la production de librairies de cibles thérapeutiques. De ce fait, le développement de nouvelles méthodes de synthèse de structures privilégiées, simples, efficaces et sensibles à l’impact environnemental reste un défi pour les chimistes. De nombreuses méthodes de synthèse requièrent l’emploi de dérivés d’anilines acylées en position ortho, mais ces substrats sont peu disponibles. La réaction d’addition en cascade, catalysée au cuivre, d’un réactif de Grignard sur l’anthranilate de méthyle permet l’obtention d’une aniline acylée en position ortho, jamais reportée au préalable, avec un rendement quantitatif. Cette dernière servira alors de substrat de départ pour la synthèse de plusieurs hétérocycles privilégiés dont les quinoléines et les indoles. La réaction de Friedlander est utilisée depuis plusieurs siècles mais souffre de l’emploi de conditions réactionnelles extrêmes et nocives pour l’environnement. Elle a donc été modernisée pour donner accès à une série de huit quinoléines trisubstituées, sans solvant, ni acide fort, ni hautes températures. Par ailleurs, le procédé de Heumann consiste en la synthèse d’indoles substitués en position par alkylation d’anilines acylées en position ortho, suivie d’une étape de saponification et de cyclisation intramoléculaire. Breveté par l’entreprise B.A.S.F., en 1895, ce procédé est rapidement devenu obsolète dû à de faibles rendements et des conditions réactionnelles difficiles. La chimie en flux continu a alors permis la renaissance de ce procédé grâce à l’élaboration d’un protocole plus efficace et plus sécuritaire. Somme toute, les travaux présentés dans cette thèse contribuent au développement de méthodologies simples, efficaces, sensibles aux enjeux environnementaux et menant à des structures plus complexes. / The heterocycle chemistry is one of the most important fields in organic chemistry. Indeed, 65% of the literature in organic chemistry is about heterocycles. They are widely present in nature, essential to life and their applications are endless. Among them, the so-called privileged structures, attract particular attention. Privileged structures, of which quinolines and indoles are a part, play a crucial role in medicinal chemistry, for the production of libraries of therapeutic targets. Therefore, the development of new synthetic methods, simple, efficient and sensitive to environmental impact remains a challenge for chemists. Many synthetic methods require the use of o-acylated anilines, but these substrates are not easily available. The copper catalyzed addition reaction of a Grignard reagent on methyl anthranilate allows to form an o-acylated aniline, never reported before, with a quantitative yield. The latter will then serve as starting material for the synthesis of several privileged heterocycles including quinolines and indoles. The Friedlander reaction has been used for several centuries but suffers from the use of extreme reaction conditions which are harmful to the environment. It has therefore been modernized to give access to a series of eight trisubstituted quinolines, without solvent, strong acid or high temperatures. Furthermore, Heumann's process consists of the synthesis of indoles substituted in position by o-acylated anilines alkylation, followed by saponification and intramolecular cyclization steps. Patented by B.A.S.F. in 1895, this process quickly became obsolete due to low yields and difficult reaction conditions. Continuous flow chemistry has resurrected this process through the development of a more efficient and safer protocol. All in all, the work presented in this thesis contributes to the development of simple, effective methodologies, sensitive to environmental issues and leading to increasingly complex structures.

Depuis les années 2000 le domaine de l’organocatalyse asymétrique est en plein développement comme le montre le nombre croissant de publications sur le sujet. Durant cet essor un grand nombre d’organocatalyseurs a été développé, ils se classent en quatre catégories : les catalyseurs de transfert de phase, les bases de Lewis, les bases de Brønsted et les acides de Brønsted. Appartenant à cette dernière catégorie, les acides phosphoriques chiraux font partie des acides de Brønsted les plus populaire. Leurs premières utilisations en organocatalyse asymétrique remontent à 2004 où des acides phosphoriques dérivés du BINOL furent utilisés par Terada et Akiyama pour catalyser des réactions de Mannich de manière hautement énantiosélective. Depuis le champ d’application des acides phosphoriques s’est considérablement étendu et aujourd’hui environ 90 réactions différentes peuvent être catalysées efficacement par ces acides. En parallèle de ce développement des équipes ont commencé à apporter des modifications structurales aux acides phosphoriques dans le but d’étendre encore leur champ d’application. L’une des approches consiste à modifier le squelette carboné afin de modifier l’organisation spatiale de l’encombrement stérique chiral autour du phosphore. Le travail présenté dans ce manuscrit décrit l’élaboration et l’utilisation en catalyse d’une nouvelle famille d’acides phosphoriques à chiralité planaire basée sur un motif [3,3]paracyclophane. L’étude commence par la modélisation par calculs DFT de différents paracyclophanes dans le but d’évaluer la tension de cycle et la barrière de rotation imprimer à la structure en fonction de l’espaceur utilisé. Trois espaceurs sont sélectionnés pour des essais en synthèse : le -CH2-NTs-CH2-, le 1,8-naphtalènediyle et le 1,1’-ferrocènediyle. Les synthèses de trois bisphénols comportant les motifs précédents sont réalisées. Les bisphénol comportant les espaceurs -CH2-NTs-CH2-, le 1,8-naphtalènediyle n’ont pas pu être transformés en acides phosphoriques. En revanche il a été possible d’obtenir une nouvelle famille d’acides phosphoriques à chiralité planaire comportant le motif 1,1’-ferrocènediyle.Par la suite une méthode de synthèse permettant la variation facile des substituants aromatiques a été mise en place ainsi qu’une méthode de séparation de diastéréoisomères à l’aide d’un auxiliaire chiral afin d’obtenir des acides phosphoriques énantiopurs. Une famille de 6 acides phosphoriques a ainsi pu être synthétisée. Ces nouveaux acides ont ensuite été testés en organocatalyse asymétrique. La réaction de réduction par des esters de Hantzsch de quinoléines substituées en position 2 a servi de réaction test. Après sélection du meilleur acide, une étude sur l’influence de l’ester de Hantzsch a été menée conduisant à une forte augmentation de l’énantiosélectivité de la réaction. Enfin le champ d’application de la réaction a été explorer et des excès énantiomériques atteignant 92% ont pu être atteints. D’autres modifications structurales peuvent être apportées à cette nouvelle structure comme par exemple le remplacement du motif 1,1’-ferrocènediyle par le motif 1,8-dibromobiphénylènyl. Une influence non négligeable de l’espaceur sur les performances du catalyseur a pu être ainsi observée.L’étude a montré le potentiel de cette nouvelle famille d’acide phosphorique en organocatalyse asymétrique. Cette nouvelle famille va donc pouvoir être utilisée pour développer de nouvelle réaction énantiosélectives et ce dans le domaine de l’organocatalyse ou bien dans celui de la catalyse organométallique en utilisant le phosphate comme contre-ion chiral. / During the first decade of the century the organocatalysis has known an intense development shown by the increasing number of publications on the subject. This development led to the apparition of a wide number of different organocatalysts. These catalysts can be sorted in three categories: the phase transfer catalysts, the Lewis bases, the Brønsted bases and the Brønsted acids. One of the most used types of organocatalysts belonging to the latter category are the chiral phosphoric acids (CPA). The first use of these CPAs as organocatalysts was published in 2004 by Terada and Akiyama. They independently reported two Mannich-type reactions catalysed by BINOL-derived CPAs with high levels of enatioselectivity. Since then CPAs appeared as versatile catalysts and to this date more than 90 different reactions can be catalysed in a highly énantiosélective manner by these acids. Meanwhile some researchers began to modify the original BINOL-based phosphoric acids so as to broaden their scope. One possible approach consists in changing the chiral backbone to change the spatial organisation of the chiral environment. The work reported in this manuscript describe the design, the synthesis and the use in organocatalysis of a new planar chiral phosphoric acids based on a [3,3]paracyclophanes scaffold. This study begins with the DFT modelling of a series of paracyclophanes in order to evaluate the ring strain and rotation barrier induced by the nature of different tethering units. Three tethers have been selected for synthesis trials: the -CH2-NTs-CH2-, the 1,8-naphtalenediyl and the 1,1’-ferrocenediyl. Three different bisphenols each one embedding one of the three tethers mentioned above have been synthesised. It was not possible to turn the -CH2-NTs-CH2- and the 1,8-naphtalenediyl-based bisphenols into the corresponding phosphoric acids. But the 1,1’-ferrocenediyl-based bisphenol was successfully cyclised into the desired planar chiral phosphoric acid. Subsequently a synthetic pathway allowing an easy variation of the aryl substituents has been developed together with the use of a chiral auxiliary to obtain the planar CPAs in an enantiopure way. By this method 6 different CPAs have been synthesised. The efficiency in asymmetric organocatalysis of these new planar CPAs was investigated. The reduction of 2-substituted quinolines by Hantzsch esters was used as a benchmark reaction. After having identified the best CPA, the role of the Hantzsch ester has been investigated leading to an important improvement of the enantioselectivity of the reaction. Eventually, the scope of the reaction has been explored and e.e.’s up to 92% have been reached. Some other structural modifications of the structure can be made such as the replacement of the 1,1’-ferrocenediyl unit by a 1,8-dibromobiphenylenyl. A non-negligible influence of the tether has been observed on the catalyst behaviour. The study has demonstrated the potential of this new class of organocatalyst in asymmetric catalysis. These planar CPAs will then be used in the developpement of new énantiosélective reaction in the domain of organocatalysis or in the domain of organometallic catalysis by using the phosphate as a chiral counter-ion

The central role of Src in the development of several malignancies including breast cancer and the accumulating evidence of its interaction with receptor tyrosine kinases (RTK), integrins and steroid receptors have identified it as an attractive therapeutic target. In the current study we have evaluated the effect of a Src/Abl kinase inhibitor SKI-606, on breast cancer growth, migration, invasion and metastasis. Treatment of human breast cancer cells MDA-MB-231 with SKI-606 caused a marked inhibition of cell proliferation, invasion and migration by inhibiting MAPK and Akt phosphorylation. For in vivo studies MDA-MB-231 cells transfected with the plasmid encoding green fluorescent protein (GFP) [MDA-MB-231-GFP] were inoculated into mammary fat pad of female BALB/c nu/nu mice. Once tumor volume reached 30-50 mm3, animals were randomized and treated with vehicle alone or 150 mg/kg of SKI-606 by daily oral gavage. Experimental animals receiving SKI-606 developed tumors of significantly smaller volume (45-54%) as compared to control animals receiving vehicle alone. Analysis of lungs, liver and spleen of these animals showed a significant decrease in GFP positive tumor metastasis in animals receiving SKI-606 at a dose that was well tolerated. Western blot analysis and immunohistochemical analysis of primary tumors showed that these effects were due to the ability of SKI-606 to block tumor cell proliferation, angiogenesis, growth factors expression and inhibition of Src mediated signalling pathways in vivo. Together the results from these studies provide compelling evidence for the use of Src inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

No description available.

The known 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones 122 were dehydrogenated using thallium(III) p-tolylsulfonate in dimethoxyethane under reflux to afford the 2-aryl-6,8-dibromoquinolin-4(1H)-ones 136. Palladium-catalyzed Sonogashira cross-coupling of the 2-aryl-6,8-dibromo-2,3-dihydroquinolin-4(1H)-ones with terminal alkynes in the presence of PdCl2(PPh3)2-CuI (as homogeneous catalyst source) and 10% Pd/C-PPh3-CuI (as heterogeneous catalyst source) catalyst mixture and NEt3 as a base and co-solvent in ethanol under reflux afforded the corresponding 6,8-dialkynyl-2-aryl-2,3-dihydroquinolin-4(1H)-ones 138 and 8-alkynyl-2-aryl-6-bromo-2,3-dihydroquinolin-4(1H)-ones 137, respectively. PdCl2-catalyzed electrophilic cyclization of the 8-alkynyl-2-aryl-6-bromo-2,3-dihydroquinolin-4(1H)-ones in acetonitrile under reflux afforded the 4-aryl-8-bromo-2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 139 or the 2-aryl-6-bromo-8-(4-hydroxybutanoyl)-2,3-dihydroquinolin-4(1H)-ones 140 from the 4-phenylethynyl-substituted or 4-alkylethynyl-substituted precursors, respectively. The 2-aryl-6,8-dibromoquinolin-4(1H)-ones 136 wturn, subjected to similar homogeneous and heterogeneous palladium catalyst sources using NEt3 as a base in DMF-water mixture under reflux and K2CO3 as a base in dioxane under reflux afforded 2,8-disubstituted 4-aryl-6-oxopyrrolo[3,2,1-ij]quinolines 143 and 2-substituted 4-aryl-8-bromo-6-oxopyrrolo[3,2,1-ij]quinolines 142, respectively. The monoalkynylated 4-aryl-8-bromo-2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 139 and 2-substituted 4-aryl-8-bromo-6-oxopyrrolo[3,2,1-ij]quinolines 142 were subsequently transformed using palladium-catalyzed Suzuki-Miyaura cross-coupling with arylboronic acids in the presence of PdCl2(PPh3)2-PCy3 catalyst mixture and K2CO3 as a base in dioxane-water mixture to afford the corresponding novel 8-substituted 2-phenyl-6H-pyrrolo[3,2,1-ij]quinolin-6-ones 141 and 2,8-disubstituted 4-aryl-6-oxopyrrolo[3,2,1-ij]quinolines 144, respectively. All the new compounds were characterized using a combination of 1H NMR, 13C NMR, IR, mass spectroscopic techniques and X-ray crystallography. / Chemistry / D. Phil. (Chemistry)

The previously described 2-aryl-4-chloro-3-iodoquinolines were prepared following literature procedure and in turn converted to the corresponding hitherto unknown 2-aryl-3-iodo-4-(phenylamino)quinoline derivatives using aniline in refluxing ethanol. These 2-aryl-3-iodo-4-(phenylamino)quinolines were reacted with allybromide in ethanol at room temperature to afford 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives. The 2-aryl-3-iodo-4-(phenylamino)quinoline and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were subjected to metal-catalysed carbon-carbon bond formations. Palladium(0)-copper iodide catalysed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinoline with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single step operation. On the other hand, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo palladium-catalysed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines. All new compounds were characterized by using a combination of NMR (1H and 13C), IR, mass spectroscopic techniques as well as elemental analysis. / Chemistry / MSc. (Chemistry)

The previously described 2-aryl-4-chloro-3-iodoquinolines were prepared following literature procedure and in turn converted to the corresponding hitherto unknown 2-aryl-3-iodo-4-(phenylamino)quinoline derivatives using aniline in refluxing ethanol. These 2-aryl-3-iodo-4-(phenylamino)quinolines were reacted with allybromide in ethanol at room temperature to afford 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives. The 2-aryl-3-iodo-4-(phenylamino)quinoline and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were subjected to metal-catalysed carbon-carbon bond formations. Palladium(0)-copper iodide catalysed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinoline with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single step operation. On the other hand, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo palladium-catalysed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines. All new compounds were characterized by using a combination of NMR (1H and 13C), IR, mass spectroscopic techniques as well as elemental analysis. / Chemistry / MSc. (Chemistry)