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Synthesis of oxadiazoline and quinazolinone derivatives and their biological evaluation as nitric oxide synthase inhibitors

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Abstract

The synthesis of two new families of compounds with oxadiazoline and quinazolinone structures and their in vitro biological evaluation as inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS) are described. These derivatives have been obtained from cyclization of substituted benzohydrazides with acid anhydrides followed by reduction, using different synthetic procedures. Their structures were confirmed by high-resolution mass spectroscopy and 1H and 13C nuclear magnetic resonance data. In general, the assayed compounds show better inhibition values of nNOS than of iNOS, being 7d the most active derivative with a quinazolinone scaffold, and 6t the best oxadiazoline one and the best nNOS inhibitor of all tested compounds. The structure–activity relationships are discussed in terms of the effects of the substituents on both 2- and 3-positions of the heterocyclic rings.

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Acknowledgments

This work was supported by Grants from the Vicerrectorado de Política Científica e Investigación de la Universidad de Granada (GREIB.PYR_2010_03 and GENIL/GREIB 2011).

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Authors and Affiliations

  1. Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Granada, Spain

    M. José Pineda de las Infantas, M. Dora Carrión, Mariem Chayah, Luisa C. López-Cara, Miguel A. Gallo & M. Encarnación Camacho

  2. Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de La Salud, Universidad de Granada, Granada, Spain

    Darío Acuña-Castroviejo

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  1. M. José Pineda de las Infantas
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  2. M. Dora Carrión
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  3. Mariem Chayah
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  4. Luisa C. López-Cara
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  5. Miguel A. Gallo
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  7. M. Encarnación Camacho
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Correspondence to M. Encarnación Camacho.

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Pineda de las Infantas, M.J., Carrión, M.D., Chayah, M. et al. Synthesis of oxadiazoline and quinazolinone derivatives and their biological evaluation as nitric oxide synthase inhibitors. Med Chem Res 25, 1260–1273 (2016). https://doi.org/10.1007/s00044-016-1568-0

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  • DOI: https://doi.org/10.1007/s00044-016-1568-0

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