Publications > Moron et al

Chem. Commun. 2012, 48, 9171

A cascade reaction of azolopyrimidines. Synthesis of unusual indole and azaindole derivatives.

María Morón¹, Carolina Burgos¹, Julio Alvarez-Builla¹, Antonio Salgado², Marta E. G. Mosquera^3, a, Juan J Vaquero^1, a

1. Departamento de Química Orgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.  2. Department of Medicinal Chemistry, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, E-28029-Madrid, Spain.  3. Departamento de Química Inorgánica Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.

a. juanjose.vaquero@uah.es

Abstract

The reaction of bromo substituted pyrido[3',2':4,5]pyrrolo-[1,2-c]pyrimidine and pyrimido[1,6-a]indole methyl carboxylates with primary amines is described. The expected amide formation occurs but it is followed by an unexpected cascade process involving attack of the amine to the pyrimidine ring, opening of the pyrimidine ring, loss of the bromine substituent and competitive cyclizations to afford unusual imidazolidene substituted indoles and azaindoles.

Publications > Ramírez et al

Org. Biomol. Chem. 2012, 10, 1659

Donor-(π-bridge)-azinium as D-π-A + one-dimensional and D-π-A +-π-D multidimensional V-shaped chromophores.

M.A. Ramírez^1, 2, 3, A.M. Cuadro, J. Alvarez-Builla, O. Castaño, J.L. Andrés, F. Mendicuti, K. Clays, I. Asselberghs, J.J. Vaquero

1. Departamento de Química Orgánica, Universidad de Alcalá, 28871, Alcalá de Henares Madrid, Spain.  2. Departamento de Química Física, Universidad de Alcalá, 28871, Alcalá de Henares Madrid, Spain.  3. Department of Chemistry, University of Leuven, Celestijnenlaan 200, D 3001, Leuven, Belgium.

Resumen

Heteroaromatic cations reacted with N-heteroarylacetylenes under Sonogashira conditions to allow easy access to potential single donor D-π-A + and V-shaped D-π-A +-π-D chromophores, where the acceptor moiety A is the π-deficient pyridinium cation and the donor moiety is represented by different π-excessive N-heterocycles. The β hyperpolarizabilities were measured using hyper-Rayleigh scattering experiments and the experimental data are supported by a theoretical analysis that combines a variety of computational procedures, including Density Functional Theory (DFT) and correlated Hartree-Fock-based methods (RCIS(D)). © 2012 The Royal Society of Chemistry.

Publications > Belayev et al

Translational Stroke Research 2012, 3, 154

Superior Neuroprotective Efficacy of LAU-0901, a Novel Platelet-Activating Factor Antagonist, in Experimental Stroke.

Ludmila Belayev, Tiffany N. Eady, Larissa Khoutorova, Kristal D. Atkins, Andre Obenaus, Marta Cordoba, Juan J. Vaquero, Julio Alvarez-Builla, Nicolas G. Bazan

Resumen

Platelet-activating factor (PAF) accumulates during cerebral ischemia, and inhibition of this process plays a critical role in neuronal survival. Recently, we demonstrated that LAU-0901, a novel PAF receptor antagonist, is neuroprotective in experimental stroke. We used magnetic resonance imaging in conjunction with behavior and immunohistopathology to expand our understanding of this novel therapeutic approach. Sprague–Dawley rats received 2 h middle cerebral artery occlusion (MCAo) and were treated with LAU-0901 (60 mg/kg) or vehicle 2 h from MCAo onset. Behavioral function, T2-weighted imaging (T2WI), and apparent diffusion coefficients were performed on days 1, 3, and 7 after MCAo. Infarct volume and number of GFAP, ED-1, and NeuN-positive cells were conducted on day 7. Behavioral deficit was significantly improved by LAU-0901 treatment compared to vehicle on days 1, 3, and 7. Total lesion volumes computed from T2WI were significantly reduced by LAU-0901 on days 1, 3, and 7 (by 83%, 90%, and 96%, respectively), which was consistent with decreased edema formation. Histopathology revealed that LAU-0901 treatment resulted in significant reduction of cortical and subcortical infarct volumes, attenuated microglial infiltration, and promoted astrocytic and neuronal survival. These findings suggest LAU-0901 is a promising neuroprotectant and provide the basis for future therapeutics in patients suffering ischemic stroke.

Publications > Suárez et al

Molecules 2012, 17, 8735

Synthesis of 9,9′-[1,2-Ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, an Impurity of Acyclovir.

Rosa M. Suárez, Maria Paz Matía, José Luis Novella, Andres Molina, Antonio Cosme, Juan José Vaquero, Julio Alvarez-Builla

Palabras clave: nucleosides; acyclovir; drug impurities; phase transfer catalysis

Resumen

The synthesis of 9,9'-[1,2-ethanediylbis(oxymethylene)]bis-2-amino-1,9-dihydro-6H-purin-6-one, a minor impurity of acyclovir, is described. Starting with commercial N-(9-acetyl-6-oxo-1H-purin-2-yl)acetamide, the process uses an acid catalysed phase transfer catalysis (PTC) process to produce the selective alkylation at the 9 position of the guanine ring.

Publications > García et al Eur. J. Med. Chem

Eur. J. Med. Chem 2012, 50, 90

New losartan-hydrocaffeic acid hybrids as antihypertensive-antioxidant dual drugs: Ester, amide and amine linkers

Gonzalo García, Isabel Serrano, Patricia Sánchez-Alonso, Manuel Rodríguez-Puyol, Ramón Alajarín, Mercedes Griera, Juan J. Vaquero, Diego Rodríguez-Puyol, Julio Álvarez-Builla, María L. Díez-Marqués

Palabras clave: Antihypertensive; Antioxidant; Hybrid drug; Hydrocaffeic acid; Losartan

Resumen

We report new examples of a series of losartan–hydrocaffeic hybrids that bear novel ester, amide and amine linkers. These compounds were made by linking hydrocaffeic acid to the side chain of losartan at the C-5 position of the imidazole ring through different strategies. Experiments performed in cultured cells demonstrate that these new hybrids retain the ability to block the angiotensin II effect and have increased antioxidant ability. Most of them reduced arterial pressure in rats better or as much as losartan.