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Theoretical design of new indole-3-carboxamide derivatives as renin inhibitors

Abstract

Renin inhibitors pertain to a new generation class of antihypertensive agents. There are only a few studies on the computational modeling of such class of compounds and only one available drug in the market used as renin inhibitor for the treatment of hypertension, aliskiren. The present study reports the QSAR modeling of the activities of a series of indole-3-carboxamide derivatives using MIA-QSAR in order to propose new promising analogs as renin inhibitor candidates. The proposed structures were submitted to docking evaluation to search for the interaction modes responsible for the calculated bioactivities. In addition, the drug likeness of the proposed compounds was investigated using theoretical data related to pharmacokinetic properties. Overall, at least two promising candidates are proposed as highly active and pharmacokinetically acceptable renin inhibitors.

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Acknowledgments

Authors are thankful to FAPEMIG for the financial support of this research, as well as to CAPES for the studentship (E.G.M.) and to CNPq for fellowships (to E.F.F.C. and M.P.F.).

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The authors declare no conflict of interest.

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Correspondence to Matheus P. Freitas.

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da Mota, E.G., Duarte, M.H., da Cunha, E.F.F. et al. Theoretical design of new indole-3-carboxamide derivatives as renin inhibitors. Med Chem Res 24, 3097–3106 (2015). https://doi.org/10.1007/s00044-015-1362-4

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  • DOI: https://doi.org/10.1007/s00044-015-1362-4

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