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Synthesis, molecular properties and DFT studies of new phosphoramidates as potential urease inhibitors

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Abstract

In this work, new phosphoramidates were prepared and screened for their putative urease inhibitory activity. The importance of this class of compounds is related to the wide range of biological activities which they exhibit. Consequently, higher activity shown by phosphoramidates 3a, 4b, 5a, 5b, 5c, and 9a suggests that they could serve as lead substances for the development of novel synthetic compounds with enhanced inhibitory ureolitic activity. Their predicted ADMET properties are also in accordance with the general requirements for drug-like compounds. Structure–activity relationship analyses suggest that the presence of cyclohexylamine group is an important structural feature associated with enhanced activities. DFT calculations were performed to obtain the energy values of HOMO and LUMO, and dipole moment.

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Acknowledgments

We are grateful to the following Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for research fellowships (AJD, CRAM, LCAB), Fundação de Amparo à Pesquisa de Minas Gerais (FAPEMIG), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and FINEP for financial support. We also thanks to Dr. Adão Sabino and Mr. Augusto Carvalho for obtaining the high resolution mass spectra.

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Authors and Affiliations

  1. Departamento de Química, Universidade Federal de Viçosa, Av. PH Rolfs, Viçosa, MG, 36570-000, Brazil

    Fabricio M. Oliveira, Luiz C. A. Barbosa, Antônio J. Demuner, Célia R. A. Maltha & Silvana R. Pereira

  2. Departamento de Química, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627, Pampulha, Belo Horizonte, MG, 31270-901, Brazil

    Luiz C. A. Barbosa

  3. Departamento de Botânica, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos 6627 – Pampulha, Belo Horizonte, MG, 31270-901, Brazil

    Lívia P. Horta & Luzia V. Modolo

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  1. Fabricio M. Oliveira
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  3. Antônio J. Demuner
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Correspondence to Luiz C. A. Barbosa.

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Oliveira, F.M., Barbosa, L.C.A., Demuner, A.J. et al. Synthesis, molecular properties and DFT studies of new phosphoramidates as potential urease inhibitors. Med Chem Res 23, 5174–5187 (2014). https://doi.org/10.1007/s00044-014-1113-y

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