Publicaciones > Abengozar et al

Eur J Org Chem. 2015 Jun 24; 6(24):4214-4223.

Azonia Aromatic Cations by Ring-Closing Metathesis: Synthesis ofAzaquinolizinium Cations.

Alberto Abengozar, Beatriz Abarca, Ana M. Cuadro, David Sucunza, Julio Álvarez‐Builla, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala , 28805 Alcala de Henares , Spain.

Abstract

A new approach for the synthesis of the 1‐azaquinolizinium (pyrimido[1,2‐a]pyrimidin‐5‐ium) heterocycle and some simple derivatives is described. This strategy, based on an unprecedented ring‐closing metathesis (RCM) reaction to construct the pyrimidinium ring, was also applied to the first reported synthesis for the benzo‐1‐azaquinolizinium (pyrimido[2,1‐a]isoquinolinium) cation.

Publicaciones > Rodríguez-Sanz et al

Eur. J. Med. Chem. 2015 Mar; :83-92.

Synthesis and biological evaluation of pyridazino[1′,6′:1,2]pyrido[3,4-b]indolinium and pyridazino[1,6-a]benzimidazolium salts as anti-inflammatory agents.

Aranzazu Rodríguez-Sanz¹, Patricia Sánchez-Alonso², Teresa Bellón¹, Ramón Alajarín², Virginia Martínez-Cabeza¹, Rafael Selgas³, Juan J. Vaquero², Julio Álvarez-Builla²

1. Instituto de Salud Hospital Universitario La Paz – IdiPAZ, Madrid, Spain.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Madrid, Spain.  3. Hospital Universitario La Paz, Servicio de Nefrología, IdiPAZ, IRSIN, Madrid, Spain.

Abstract

Condensed polycyclic heteroaromatic cations bearing a bridgehead nitrogen with pyridazino[1′,6′:1,2]pyrido[3,4-b]indolinium and pyridazino[1,6-a]benzimidazolium structures were assayed as inhibitors of LPS-induced TNF-α production by THP-1 cells. The hit compound 1e, which had the best IC50 value (4.49 μM) and low toxicity, was further assayed on human PMBCs (IC50 3.91 μM) and monocytes (IC50 1.82 μM). This compound also inhibited TNF-α production following poly I:C stimulation of human monocytes and monocyte-derived dendritic cells; in the latter case, inhibition of IL-12 production was also observed. Compound 1e was also able to inhibit TNF-α expression at the transcriptional level and proved to be effective in vivo. Compound 1e is an interesting potential therapeutic agent in IMIDs.

Publicaciones > Abarca et al

Org Lett. 2014 Jul 3;16(13):3464-7. doi: 10.1021/ol5013668. PubMed 24940996

Efficient synthesis of an indoloquinolizinium alkaloid selective DNA-binder by ring-closing metathesis.

Beatriz Abarca, Raul Custodio, Ana M Cuadro, David Sucunza, Alberto Domingo, Francisco Mendicuti, Julio Alvarez-Builla, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, double daggerDepartamento de Biologia de Sistemas, section signDepartamento de Quimica Analitica, Quimica Fisica e Ingenieria Quimica, Universidad de Alcala , 28871-Alcala de Henares, Madrid, Spain.

Abstract

Two total syntheses of the indolo[2,3-a]quinolizinium cation have been accomplished through the application of two ring-closing metathesis reactions to form the pyridinium ring. One of these approaches provides the tetracyclic cation in only five steps from commercially available harmane. Fluorescence-based thermal denaturation experiments, as well as spectrofluorimetric titration, circular dichroism measurements, and theoretical simulations, showed a consistent DNA-binding capacity by intercalation with a marked preference for AT-rich sequences.

Publicaciones > Sanchez et al

Org Biomol Chem. 2014 Jun 28;12(24):4233-42. doi: 10.1039/c4ob00175c. PubMed 24838636

Microwave-assisted synthesis of potent PDE7 inhibitors containing a thienopyrimidin-4-amine scaffold.

Ana I Sanchez, Ricardo Meneses, Jose M Minguez, Araceli Nunez, Rafael R Castillo, Fabiana Filace, Carolina Burgos, Juan J Vaquero, Julio Alvarez-Builla, Alvaro Cortes-Cabrera, Federico Gago, Emma Terricabras, Victor Segarra

Departamento de Quimica Organica, Universidad de Alcala, E-28871 Alcala de Henares, Madrid, Spain. julio.alvarez.@uah.es.

Abstract

A series of novel thienopyrimidin-4-amines have been synthesized and evaluated as phosphodiesterase (PDE) inhibitors. A rationale for the observed selectivity against PDE7 has been obtained from molecular modelling studies on the most active compounds.

Publicaciones > Carmona et al

Dyes and Pigments. 2014 Apr 1; :106-117. doi: 10.1016/j.dyepig.2013.12.003

Cucurbit[n]urils as a potential fine-tuned instrument for modifying photophysical properties of D–π–A+–π–D “push–pull” chromophores.

Thais Carmona¹, Tatiana Cañeque², Raul Custodio², Ana M. Cuadro², Juan J Vaquero², Francisco Mendicuti¹

1. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.

Abstract

Photophysical properties of supramolecular complexes between cucurbit[7]uril (CB[7]) and one- (1D, linear) and two-dimensional (2D, V-shaped) D–π–A+–π–D pyridinium (A+) based “push–pull” chromophores, were investigated by UV–Vis and fluorescence techniques, as well as Molecular Mechanics and Molecular Dynamics simulations. Both chromophores formed stable complexes with CB[7] of different stoichiometries. Complexation was accompanied by significant changes in the photophysical properties of the guests: (i) bathochromic shifts for the π–π* charge transfer absorption band, which is more evident for the 1D than for the V-shaped one, (ii) significant enhancement of the fluorescence intensity, (iii) displacement to the blue of the emission and (iv) change in their fluorescence lifetimes, which is more patent for the V-shaped one. 1D chromophore/CB[7] complex formation was both enthalpically and entropically favored, whereas inclusion of the V-shaped one, accompanied by a little positive enthalpy change, was entropically governed. Variation of fluorescence lifetime and fluorescence anisotropy upon complexation exhibited quite different behaviors. MM and MD calculations were performed to simulate the complexation processes in the presence of water, determine their preferred structures and establish the host:guest interactions responsible for the complexes formation which were preferentially electrostatics.

Publicaciones > Cañeque et al

Dyes and Pigments. 2014 Feb 1; :116-121. doi: 10.1016/j.dyepig.2013.09.031

Novel charged NLO chromophores based on quinolizinium acceptor units.

Tatiana Cañeque¹, Ana M. Cuadro¹, Julio Alvarez-Builla¹, Julio Alvarez-Builla², Javier Pérez-Moreno³, Koen Clays³, Obis Castaño⁴, José L. Andrés⁵, Juan J Vaquero¹

1. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  2. Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871, Alcalá de Henares, Madrid, Spain.  3. Department of Chemistry, University of Leuven, Celestijnenlaan 200 D, B-3001, Belgium.  4. Departamento de Química Analítica, Química Física e Ingeniería Química, Universidad de Alcalá, 28871 Alcalá de Henares, Madrid, Spain.  5. IES Matarraña, 44580 Valderrobres, Teruel, Spain.

Abstract

An azonia cation has been explored for the first time as an acceptor unit in charged π-donor π-acceptor chromophores. Initial experimental and theoretical data show that quinolizinium, the simplest heteroaromatic azonia cation, behaved as a good acceptor unit and conferred promising nonlinear optical properties to simple push–pull cationic chromophores.

Publicaciones > Coppola et al

Org Lett. 2013 Jul 5;15(13):3388-91. doi: 10.1021/ol401433x. PubMed 23795915

Remote aryl cyanation via isocyanide-cyanide rearrangement on tosylmethyl isocyanide derivatives.

Anna Coppola, Patricia Sanchez-Alonso, David Sucunza, Carolina Burgos, Ramon Alajarin, Julio Alvarez-Builla, Marta E G Mosquera, Juan J Vaquero

Departamento de Quimica Organica y Quimica Inorganica, Universidad de Alcala, 28871 - Alcala de Henares, Madrid, Spain.

Abstract

The reaction of alkyl tosylmethyl isocyanides and 2-bromobenzyl bromides in the presence of t-BuLi gives rise to a cascade reaction to give unexpected 2-substituted 2,3-dihydro-1H-indenimines which, upon treatment with t-BuOK, rearrange to 2-vinylbenzonitriles in high overall yields. This simple procedure represents a new approach to the synthesis of aromatic nitriles via isocyanide-cyanide interconversion.