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Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: rational design, synthesis and biological evaluation

Amino Acids volume 40, pages 411–420 (2011)Cite this article

Abstract

A series of o-, m- and p-benzyl tetrazole derivatives 11a–c has been designed, synthesized and evaluated as potential Angiotensin II AT1 receptor antagonists, based on urocanic acid. Compound 11b with tetrazole moiety at the m-position showed moderate, however, higher activity compared to the o- and p-counterpart analogues. Molecular modelling techniques were performed in order to extract their putative bioactive conformations and explore their binding modes.

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Acknowledgments

This research project was supported by the Ministry of Development, General Secretariat of Research and Technology of Greece [EPAN: “IRAKLIS” YB 84 (B321/2005)]. We thank Dr Andreas Papapetropoulos for providing primary rat aortic smooth muscle cells (RASMC). Also, we would like to thank Dimitris Vahliotis (Instrumental Analysis Laboratory, University of Patras) for recording the NMR spectra.

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Affiliations

  1. Department of Chemistry, University of Patras, 26500, Patras, Greece

    George Agelis, Amalia Resvani, Minos-Timotheos Matsoukas, Theodore Tselios, Konstantinos Kelaidonis & John Matsoukas

  2. Department of Pharmacology, School of Medicine, University of Patras, 26500, Patras, Greece

    Dimitra Kalavrizioti

  3. Department of Internal Medicine, ‘ATTIKON’ University Hospital, Athens, Greece

    Demetrios Vlahakos

Authors
  1. George Agelis
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  2. Amalia Resvani
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  3. Minos-Timotheos Matsoukas
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  4. Theodore Tselios
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  5. Konstantinos Kelaidonis
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  6. Dimitra Kalavrizioti
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  7. Demetrios Vlahakos
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  8. John Matsoukas
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Correspondence to George Agelis or John Matsoukas.

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Agelis, G., Resvani, A., Matsoukas, MT. et al. Towards non-peptide ANG II AT1 receptor antagonists based on urocanic acid: rational design, synthesis and biological evaluation. Amino Acids 40, 411–420 (2011). https://doi.org/10.1007/s00726-010-0651-y

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  • DOI: https://doi.org/10.1007/s00726-010-0651-y

Keywords

  • AT1 receptor
  • Urocanic acid
  • Pharmacophore
  • Molecular modelling