Compost de N-azolilpidridini amb possible activitat antiparasitària: síntesi i propietats

Tesi de Llicenciatura per a la obtenció del Grau de Farmàcia. Facultat de Farmàcia. Universitat de Barcelona. Director: Ma. Ermitas Alcalde Pais. 1984.Donades les conseqüències incalculables en el domini de la salut, i els enormes interessos financers en joc , el tema dels antiparasitaris, humans i animals, ha estat objecte de nombrossos treballs per part de poderoses empreses farmacèutiques multinacionals. Dades recents assenyalen que la infecció per Trichomonas vaginalis té una incidència mundial del 10 al 90 % de la població. Per la seva part, la malaltia de Chagas, causada per Tripanosoma cruzi, afecta 7 milions de persones a Sudamèrica, i que uns 35 milions més estan amenaçats d'agafar-la

Synthetic approaches to multifunctional indenes

The synthesis of multifunctional indenes with at least two different functional groups has not yet been extensively explored. Among the plausible synthetic routes to 3,5-disubstituted indenes bearing two different functional groups, such as the [3-(aminoethyl)inden-5-yl)]amines, a reasonable pathway involves the (5-nitro-3-indenyl)acetamides as key intermediates. Although several multistep synthetic approaches can be applied to obtain these advanced intermediates, we describe herein their preparation by an aldol-type reaction between 5-nitroindan-1-ones and the lithium salt of N,N-disubstituted acetamides, followed immediately by dehydration with acid. This classical condensation process, which is neither simple nor trivial despite its apparent directness, permits an efficient entry to a variety of indene-based molecular modules, which could be adapted to a range of functionalized indanones

Azolium-based systems: application of an anion exchange resin (A- form) method and 1H NMR analysis of the charged-assisted (C<br>H)+·anion hydrogen bonds

The counteranion exchange of quaternary 1,2,3-triazolium salts was examined using a simple method that permitted halide ions to be swap for a variety of anions using an anion exchange resin (A¯ form). The method was applied to 1,2,3-triazolium-based ionic liquids and the iodideto- anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Additionally, an anion exchange resin (N3¯ form) was used to obtain the benzyl azide from benzyl halide under mild reaction. Likewise, following a similar protocol, bis(azidomethyl)arenes were also synthesized in excellent yields. The results of a proton NMR spectroscopic study of simple azolium-based ion pairs are discussed, with attention focused on the significance of the charged-assisted (CH)+···anion hydrogen bonds of simple azolium systems such as 1-butyl-3-methylimidazolium and 1-benzyl-3-methyl-1,2,3-triazolium salts

Betaínas heterocíclicas y derivados: una nueva clase de agentes antiprotozoarios: síntesis, estructura y propiedades

[spa] La tesis doctoral constituye la prospección previa realizada de un programa de investigación sobre la química de las betaínas heterocíclicas, cuyas ideas generales giran fundamentalmente alrededor del eje formado por la química heterocíclica y la química terapéutica. Las betaínas heterocíclicas forman un conjunto de compuestos en los que la originalidad de las estructuras moleculares ofrece un excelente potencial investigador. Se describe la síntesis de una serie de betaínas heterocíclicas de azolato piridinio, azolato azolio y 1-alquil-4-azoliden-1,4- dihidropiridinas, y sus derivados, conjunto de compuestos prácticamente desconocido en la literatura química y que pueden considerarse de manera formal como azaanálogos del sesquifulvaleno. Se han realizado ensayos de su actividad biológica frente a diversos parásitos, y se observa que son particularmente activos frente Leishmania donovani y Trypanosoma cruzi, y se pueden considerar las sales de N-aziolilpiridinio como una nueva clase de agentes antiprotozoarios. Asimismo, se ha llevado a cabo un minucioso estudio estructural de los nuevos compuestos sintetizados. La estructura de las betaínas heterocíclicas se analiza en base a los resultados de los cálculos teóricos (MNDO), datos espectroscópicos, momentos dipolares experimentales y análisis por difracción de rayos X. La estructura altamente dipolar de las betaínas heterocíclicas se refleja en sus elevados momentos dipolares experimentales (los mas altos para moléculas orgánicas sencillas). Por otra parte se ha iniciado el estudio de su reactividad frente a electrófilos y frente a dipolarófilos, describiéndose por primera vez una reacción de cicloadición dipolar de una betaína mesomera heterocíclica, azaderivada de la forma dipolar del N-iluro del ciclopentadienuro de piridinio

Aplicació terapèutica dels compostos organometal·lics

In recent years, organometallic chemistry has acquired an important role in clinical practice, although it exists a wide variety of organic structures linked to metals in nature, and involved in biological processes. The most commonly used metals in therapy are Fe, Ag and Au even though studies with other metals, such as Ru and Rh, are increasing. The organometallic compounds have been evaluated as chemotherapeutic, antibacterial agents, radioimaging and fluorescence agents, among other applications. Ferrocene derivatives or N-heterocyclic carbenes (NHC) are structures with greater potential in these areas. This work is a review of the applications of organometallic compounds families and is highlighted the features from those that have stood out in their application field

Aplicació terapèutica dels compostos organometal·lics

In recent years, organometallic chemistry has acquired an important role in clinical practice, although it exists a wide variety of organic structures linked to metals in nature, and involved in biological processes. The most commonly used metals in therapy are Fe, Ag and Au even though studies with other metals, such as Ru and Rh, are increasing. The organometallic compounds have been evaluated as chemotherapeutic, antibacterial agents, radioimaging and fluorescence agents, among other applications. Ferrocene derivatives or N-heterocyclic carbenes (NHC) are structures with greater potential in these areas. This work is a review of the applications of organometallic compounds families and is highlighted the features from those that have stood out in their application field

A simple halide-to-anion exchange method for heteroaromatic salts and ionic liquids

A broad and simple method permitted halide ions in quaternary heteroaromatic and ammonium salts to be exchanged for a variety of anions using an anion exchange resin (A− form) in non-aqueous media. The anion loading of the AER (OH− form) was examined using two different anion sources, acids or ammonium salts, and changing the polarity of the solvents. The AER (A− form) method in organic solvents was then applied to several quaternary heteroaromatic salts and ILs, and the anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Relying on the hydrophobicity of the targeted ion pair for the counteranion swap, organic solvents with variable polarity were used, such as CH3OH, CH3CN and the dipolar nonhydroxylic solvent mixture CH3CN:CH2Cl2 (3:7) and the anion exchange was equally successful with both lipophilic cations and anions

Heterocyclic betaines. XXII. Azinium(azolium) 4-nitrobenzimidazolate inner salts and their derivatives with several interannular spacers. Synthesis, characterization and antitrichomonal activity

The synthesis of an ensemble of pyridinium(imidazolium) 4-nitrobenzimidazolate bentaines and their derivatives with several interannular linkages has been explored. Their antiprotozoal activity has also been examined

Synthetic approaches to multifunctional indenes

The synthesis of multifunctional indenes with at least two different functional groups has not yet been extensively explored. Among the plausible synthetic routes to 3,5-disubstituted indenes bearing two different functional groups, such as the [3-(aminoethyl)inden-5-yl)]amines, a reasonable pathway involves the (5-nitro-3-indenyl)acetamides as key intermediates. Although several multistep synthetic approaches can be applied to obtain these advanced intermediates, we describe herein their preparation by an aldol-type reaction between 5-nitroindan-1-ones and the lithium salt of N,N-disubstituted acetamides, followed immediately by dehydration with acid. This classical condensation process, which is neither simple nor trivial despite its apparent directness, permits an efficient entry to a variety of indene-based molecular modules, which could be adapted to a range of functionalized indanones

Azolium-based systems: application of an anion exchange resin (A- form) method and 1H NMR analysis of the charged-assisted (C<br>H)+·anion hydrogen bonds

The counteranion exchange of quaternary 1,2,3-triazolium salts was examined using a simple method that permitted halide ions to be swap for a variety of anions using an anion exchange resin (A¯ form). The method was applied to 1,2,3-triazolium-based ionic liquids and the iodideto- anion exchange proceeded in excellent to quantitative yields, concomitantly removing halide impurities. Additionally, an anion exchange resin (N3¯ form) was used to obtain the benzyl azide from benzyl halide under mild reaction. Likewise, following a similar protocol, bis(azidomethyl)arenes were also synthesized in excellent yields. The results of a proton NMR spectroscopic study of simple azolium-based ion pairs are discussed, with attention focused on the significance of the charged-assisted (CH)+···anion hydrogen bonds of simple azolium systems such as 1-butyl-3-methylimidazolium and 1-benzyl-3-methyl-1,2,3-triazolium salts