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Synthesis and biological evaluation of a new class of triazin–triazoles as potential inhibitors of human farnesyltransferase

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Abstract

A new synthesis of ethynyldimethoxytriazine 1, an important platform-compound for developing new chemical entities for anticancer research and for other biological applications, is described. Compound 1 was further reacted with azides 5a–i to provide triazin–triazoles 2a–i, which were tested on human farnesyltransferase and on the NCI-60 human tumor cell lines. Synthesis of other dimethoxytriazine derivatives 15 and 16, linked to a sp 2 or a sp 3 carbon atom were also studied.

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Fig. 1
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Notes

  1. CCDC-1045377 (for zinc derivative 3b) and CCDC-1045376 (for phenothiazine derivative 16) contain the crystallographic data for this contribution. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

  2. Acids 7a–d were obtained by saponification of the corresponding known esters.

  3. For additional proof on the electronic behavior of acetylene group of compound 1, see [65].

  4. For activating groups in accelerating reactivity of compounds bearing a triple bond group, see [66].

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Acknowledgments

This work was supported by the strategic Grant POSDRU/159/1.5/S/137750, Project “Doctoral and Postdoctoral programs support for increased competitiveness in Exact Sciences research,” co-financed by the European Social Fund within the Sectorial Operational Program Human Resources Development 2007–2013 (Ph. D. scholarship L. L.). The authors acknowledge the National Cancer Institute (NCI) for biological evaluation of compounds on their 60-cell panel: the testing was performed by the Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis (the URL to the Program’s website: http://dtp.cancer.gov).

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Authors and Affiliations

  1. Department of Organic Chemistry, Faculty of Chemistry, ‘Al. I. Cuza’ University of Iasi, B-dul Carol I, Nr. 11, Corp A, 700506, Iasi, Romania

    Liliana Lucescu, Elena Bîcu, Dalila Belei & Alina Ghinet

  2. ‘Petru Poni’ Institute of Macromolecular Chemistry, 41A Grigore Ghica Voda Alley, 700487, Iasi, Romania

    Sergiu Shova

  3. Inserm, U995-LIRIC, Faculté de Médecine - Pôle Recherche, Université Lille 2, CHRU de Lille, Place Verdun, 59045, Lille Cedex, France

    Benoît Rigo, Philippe Gautret & Alina Ghinet

  4. UCLille, Laboratoire de Pharmacochimie, Hautes Etudes d’Ingénieur (HEI), 13 rue de Toul, 59046, Lille, France

    Benoît Rigo, Philippe Gautret & Alina Ghinet

  5. Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, UPR2301 CNRS, Avenue de la Terrasse, 91198, Gif-sur-Yvette Cedex, France

    Joëlle Dubois

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  1. Liliana Lucescu
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Correspondence to Alina Ghinet.

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Lucescu, L., Bîcu, E., Belei, D. et al. Synthesis and biological evaluation of a new class of triazin–triazoles as potential inhibitors of human farnesyltransferase. Res Chem Intermed 42, 1999–2021 (2016). https://doi.org/10.1007/s11164-015-2131-1

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