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New 5-ylidene rhodanine derivatives based on the dispacamide A model

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Abstract

A practical approach for the preparation of (\(5Z\)) 5-ylidene rhodanine derivatives bearing the (4,5-dihalogeno-pyrrol-2-yl)carbamoyl fragment of dispacamide A is reported. The new compounds were obtained in good yields (19–88 %) by Knoevenagel condensation according to a solution-phase microwave dielectric heating protocol in the presence of organic bases (piperidine, TEA, and AcONa) from a set of \(N\)-substituted rhodanines 2(ai). The ten synthetic products 3(aj) have been synthesized with a \(Z\)-geometry about their exocyclic double bond and the structure of one of these compounds (3) was confirmed by a single X-ray diffraction analysis. The new (\(5Z\)) 5-ylidene rhodanine derivatives 3(aj) were tested against eight protein kinases.

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References

  1. Hotta N, Akanuma Y, Kawamori R, Matsuoka K, Oka Y, Shichiri M, Toyota T, Nakashima M, Yoshimura I, Sakamoto N, Shigeta Y (2006) Long-term clinical effects of Epalrestat, an aldose reductase inhibitor, on diabetic peripheral neuropathy. Diabetes Care 29:1538–1544. doi:10.2337/dc05-2370

    Article  CAS  PubMed  Google Scholar 

  2. El-Kabbani Ruiz F, Darmanim C, Chung RP-T (2004) Aldose reductase structures: implications for mechanism and inhibition. Cell Mol Life Sci 61:750–752. doi:10.1007/s00018-003-3403-2

    Article  CAS  PubMed  Google Scholar 

  3. Heng S, Tieu W, Hautmann S, Kuan K, Pedersen DS, Pietsch M, Güutschow M, Abell AD (2011) New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds. Bioorg Med Chem 19:7453–7463. doi:10.1016/j.bmc.2011.10.042

    Article  CAS  PubMed  Google Scholar 

  4. Degterev A, Lugovskoy A, Cardone M, Mulley B, Wagner G, Mitchison T, Yuan J (2001) Identification of small-molecule inhibitors of interaction between the BH3 domain and Bcl-x\(_{L}\). Nat Cell Biol 3:173–182. doi: 10.1038/35055085

    Article  CAS  PubMed  Google Scholar 

  5. Wang L, Kong F, Kokoski CL, Andrews DW, Xing C (2008) Development of dimeric modulators for anti-apoptotic Bcl-2 proteins. Bioorg Med Chem Lett 18:236–240. doi:10.1016/j.bmcl.2007.10.088

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Summerer D, Rudinger N-Z, Ilka Detmer I, Marx A (2005) Enhanced fidelity in mismatch extension by DNA polymerase through directed combinatorial enzyme design. Angew Chem Int Ed 44:4712–4715. doi:10.1002/anie.200500047

    Article  CAS  Google Scholar 

  7. Strittmatter T, Bareth B, Immel TA, Huhn T, Mayer TU, Marx A (2011) Small molecule inhibitors of human DNA polymerase \(\lambda \). Chem Biol 6:314–319. doi: 10.1021/cb100382m

    CAS  Google Scholar 

  8. Bulic B, Pickhardt M, Schmidt B, Mandelkow EM, Waldmann H, Mandelkow E (2009) Development of tau aggregation inhibitors for Alzheimer’s disease. Angew Chem Int Ed 48:1740–1752. doi:10.1002/anie.200802621

    Article  CAS  Google Scholar 

  9. Bulic B, Pickhardt M, Mandelkow EM, Mandelkow E (2010) Tau protein and tau aggregation inhibitors. Neuropharmacology 59:276–289. doi:10.1016/j.neuropharm.2010.01.016

    Article  CAS  PubMed  Google Scholar 

  10. Mishra R, Bulic B, Sellin D, Jha S, Waldmann H, Winter R (2008) Small-molecule inhibitors of islet amyloid polypeptide fibril formation. Angew Chem Int Ed 47:4679–4682. doi:10.1002/anie.200705372

    Article  CAS  Google Scholar 

  11. Whitesitt C-A, Simon R-L, Reel J-K, Sigmund S-K, Phillips M-L, Shadle J-K, Heinz L-J, Koppel G-A, Hunden D-C, Lifer S-L, Berry D, Ray J, Little S-P, Liu X, Marshall W-S, Panetta J-A (1996) Synthesis and structure–activity relationships of benzophenones as inhibitors of cathepsin D. Bioorg Med Chem Lett 6:2157–2162. doi:10.1016/0960-0894X(96)00393-9

    Google Scholar 

  12. Kumar G, Parasuraman P, Sharma SK, Banerjee T, Karmodiya K, Surolia N, Surolia A (2007) Discovery of a rhodanine class of compounds as inhibitors of Plasmodium falciparum enoyl–acyl carrier protein reductase. J Med Chem 50:2665–2675. doi:10.1021/jm061257w

    Article  CAS  PubMed  Google Scholar 

  13. Soltero-Higgin M, Carlson E-E, Phillips J-H, Kiessling L-L (2004) Identification of inhibitors for UDP-galactopyranose mutase. J Am Chem Soc 126:10532–10533. doi:10.1021/ja048017v

    Article  CAS  PubMed  Google Scholar 

  14. Powers J-P, Piper D-E, Li Y, Mayorga V, Anzola J, Chen J-M, Jaen J-C, Lee G, Liu J, Peterson M-G, Tonn G-R, Ye Q, Walker NPC, Wang Z (2006) SAR and mode of action of novel non-nucleoside inhibitors of hepatitis C NS5b RNA polymerase. J Med Chem 49:1034–1046. doi:10.1021/jm050859x

    Article  CAS  PubMed  Google Scholar 

  15. Rajamaki S, Innitzer A, Falciani C, Tintori C, Christ F, Witvrouw M, Debyser Z, Massa S, Botta M (2009) Exploration of novel thiobarbituric acid-, rhodanine- and thiohydantoin-based HIV-1 integrase inhibitors. Bioorg Med Chem Lett 19:3615–3618. doi:10.1016/j.bmcl.2009.04.132

    Article  CAS  PubMed  Google Scholar 

  16. Dayam R, Sanchez T, Neamati N (2005) \(\beta \)-Diketo acid pharmacophore. 1. Discovery of structurally diverse inhibitors of HIV-1 integrase inhibitors. J Med Chem 48:111–120. doi: 10.1021/jm0496077

    Article  CAS  PubMed  Google Scholar 

  17. Kodimuthali A, Jabaris SSL, Pal M (2008) Recent advances on phosphodiesterase 4 inhibitors for the treatment of asthma and chronic obstructive pulmonary disease. J Med Chem 51:5471–5885. doi:10.1021/jm800582j

    Article  CAS  PubMed  Google Scholar 

  18. Sherida L, Johnson SL, Chen L-H, Harbach R, Sabet M, Savinov A, Cotton NJH, Strongin A, Guiney D, Pellecchia M (2008) Rhodanine derivatives as selective protease inhibitors against bacterial toxins. Chem Biol Drug Des 71:131–139. doi:10.1111/j.1747-0285.2007.00617.x

    Article  Google Scholar 

  19. Bazureau J-P, Carreaux F, Renault S, Meijer L, Lozach O, Patent WO 2009/05032 A2, 23 April 2009. Demande PCT/FR 2008/001152, 01 October 2008

  20. Debdab M, Renault S, Lozach O, Meijer L, Paquin L, Carreaux F, Bazureau J-P (2010) Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors. Eur J Med Chem 45:805–810. doi:10.1016/j.ejmech.2009.10.009

    Article  CAS  PubMed  Google Scholar 

  21. Debdab M, Carreaux F, Renault S, Soundararajan M, Federov O, Lozach O, Babault L, Baratte B, Ogawa Y, Hagiwara M, Einsenreich A, Rauch U, Knapp S, Meijer L, Bazureau J-P (2011) Leucettines, a class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing. J Med Chem 54:4172–4186. doi:10.1021/jm200274d

    Article  CAS  PubMed  Google Scholar 

  22. Tahtouh T, Federov O, Soundararajan M, Burgy G, Durieu E, Lozach O, Cochet C, Schmid R-S, Lo D-C, Delhommel F, Oberholzer A-E, Pearl L-H, Carreaux F, Bazureau J-P, Knapp S, Meijer L (2012) Selectivity, cocrystal structures, and neuroprotective properties of leucettines, a family of protein kinase inhibitors derived from the marine sponge alkaloid leucettamine B. J Med Chem 55:9312–9330. doi:10.1021/jm301034u

    Article  CAS  PubMed  Google Scholar 

  23. Burgy G, Tahtouh T, Durieu E, Josselin-Foll B, Limanton E, Meijer L, Carreaux F, Bazureau J-P (2013) Chemical synthesis and biological validation of immobilized protein kinase inhibitory leucettines. Eur J Med Chem 62:728–737. doi:10.1016/j.ejmech.2013.01.035

    Article  CAS  PubMed  Google Scholar 

  24. Cafieri F, Fattorusso E, Mangoni A, Taglialatela-Scafati O (1996) Dispacamides, anti-Histamine alkaloids from Caribbean Agelas Sponges. Tetrahedron Lett 37:3587–3590. doi:10.1016/0040-4039(96)00629-6

    Google Scholar 

  25. Guiheneuf S, Paquin L, Carreaux F, Durieu E, Meijer L, Bazureau J-P (2012) An efficient approach to dispacamide A and its derivatives. Org Biomol Chem 10:978–987. doi:10.1039/c1ob06161e

    Article  CAS  PubMed  Google Scholar 

  26. Guiheneuf S, Paquin L, Carreaux F, Durieu E, Meijer L, Bazureau J-P (unpublished results)

  27. de la Hoz A, Loupy A (eds) (2012) Microwave in organic synthesis. Wiley-VCH, Weinheim. ISBN 978-3-527-33116-1

  28. Bazureau J-P, Draye M (eds) (2011) Ultrasound and microwave: recent advances in organic chemistry. Research Signpost, Kerala. ISBN 978-81-7895-532-2

  29. Radi M, Botta M, Falchi F, Maga G, Baldanti F, Paolucci S, Patent WO 2011/039735, 07 April 2011. Demande PCT/IT 2010/054475, 04 October 2010

  30. Kamila S, Biehl ER (2012) Microwave-assisted synthesis of novel bis(2-thioxothiazolidin-4-one) derivatives as potential GSK-3 inhibitors. Tetrahedron Lett 53:3998–4003. doi:10.1016/j.tetlet.2012.05.088

    Article  CAS  Google Scholar 

  31. Nitsche C, Klein CD (2012) Aqueous microwave-assisted one-pot synthesis of N-substituted rhodanines. Tetrahedron Lett 53:5197–5201. doi:10.1016/j.tetlet.2012.07.002

    Article  CAS  Google Scholar 

  32. Heng S, Tieu W, Hautmann S, Kuan K, Pedersen DS, Pietsch M, Gütschow M, Abell AD (2011) New cholesterol esterase inhibitors based on rhodanine and thiazolidinedione scaffolds. Bioorg Med Chem 19:7453–7463. doi:10.1016/j.bmc.2011.10.042

    Article  CAS  PubMed  Google Scholar 

  33. Safonov I-G, Heerding D-A, Keenan R-M, Price A-T, Erickson-Muller C-L, Hopson C-B, Levin J-L, Lord K-A, Tapley P-M (2006) New benzimidazoles as thrombopoietin receptor agonists. Bioorg Med Chem Lett 16:1212–1216. doi:10.1016/j.bmcl.2005.11.096

    Article  CAS  PubMed  Google Scholar 

  34. Tomašić T, Zidar N, Rupnik V, Kovač A, Blanot D, Gobec S, Kikelj D, Mašič LP (2009) Synthesis and biological evaluation of new glutamic acid-based inhibitors of MurD ligase. Bioorg Med Chem Lett 19:153–157. doi:10.1016/j.bmcl.2008.10.129

    Article  PubMed  Google Scholar 

  35. Tomašić T, Zidar N, Mueller-Premru M, Kikelj D, Mašič LP (2010) Synthesis and antibacterial activity of 5-ylidenethiazolidin-4-ones and 5-benzylidene-4,6-pyrimidinediones. Eur J Med Chem 45:1667–1672. doi:10.1016/j.ejmech.2009.12.030

    Article  PubMed  Google Scholar 

  36. Zidar N, Tomasic T, Sink R, Rupnik V, Kovac A, Turk S, Patin D, Blanot D, Contreras Martel C, Dessen A, Mueller-Premru M, Zega A, Gobec S, Peterlin Masic L, Kikelj D (2010) Discovery of novel 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD ligase. J Med Chem 53:6584–6594. doi:10.1021/jm100285g

    Article  CAS  PubMed  Google Scholar 

  37. Zidar N, Tomašić T, Šink R, Kovač A, Patin D, Blanot D, Contreras-Martel C, Dessen A, Mueller-Premru M, Zega A, Gobec S, Mašič LP, Kikelj D (2011) New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: design, synthesis, crystal structures, and biological evaluation. Eur J Med Chem 46:5512–5523. doi:10.1016/j.ejmech.2011.09.017

    Article  CAS  PubMed  Google Scholar 

  38. Chen H, Fan Y-H, Natarajan A, Guo Y, Iyasere J, Harbinski F, Luis L, Christ W, Aktas H, Halperin J (2004) Synthesis and biological evaluation of thiazolidine-2,4-dione and 2,4-thione derivatives as inhibitors of translation initiation. Bioorg Med Chem Lett 14:5401–5405. doi:10.1016/j.bmcl.2004.08.017

    Article  CAS  PubMed  Google Scholar 

  39. Whitesitt CA, Simon RL, Reel Jon K, Sigmund SK, Phillips ML, Shadle JK, Heinz LJ, Koppel GA, Hundel DC, Lifer SL, Berry D, Ray J, Little SP, Liu X, Marshall W (1996) Synthesis and structure–activity relationships of benzophenones as inhibitors of cathepsin D. Bioorg Med Chem Lett 6:2157–2162. doi:10.1016/0960-894X(96)00393-9

    Google Scholar 

  40. Lee B, Jung ME, Wolf MC, Zhang T, Patent WO 2010/044924, 22 April 2010. Demande PCT/US 2009/047854, 18 June 2009

  41. Opletalova V, Dolezel J, Kralova K, Pesko M, Kunes J, Jampilek J (2011) Synthesis and characterization of (\(Z)\)-5-arylmethylidenerhodanines with photosynthesis-inhibiting properties. Molecules 16:5207–5227. doi: 10.3390/molecules16065207

    Article  CAS  PubMed  Google Scholar 

  42. Alizadeh A, Khodaei MM, Eshghi A (2010) A solvent-free protocol for the green synthesis of arylalkylidene rhodanines in a task-specific ionic liquid. Can J Chem 88:514–518. doi:10.1139/V10-011

    Article  CAS  Google Scholar 

  43. Gong K, He ZW, Xu Y, Fang D, Liu Z-L (2008) Green synthesis of 5-benzylidene rhodanine derivatives catalyzed by 1-butyl-3-methyl imidazolium hydroxide in water. Monatsh Chem 139:913–915. doi:10.1007/s00706-008-0871-y

    Article  CAS  Google Scholar 

  44. Ben-Alloum A, Bakkas S, Bougrin K, Soufiaoui M (1998) Synthèse de nouvelles spiro-rhodanine-pyrazolines par addition dipolaire-1,3 de la diphenylnitrilimine sur quelques 5-arylidènerhodanines en ”milieu sec” et sous irradiation micro-onde. New J Chem 22:809–812. doi:10.1039/A803447H

    Article  CAS  Google Scholar 

  45. Sing WT, Lee CL, Yeo SL, Lim SP, Sim MM (2001) Arylalkylidene rhodanine with bulky and hydrophobic functional group as selective HCV NS3 protease inhibitor. Bioorg Med Chem Lett 11:91–94. doi:10.1016/S0960-894X(00)00610-7

    Google Scholar 

  46. Altomare A, Burla MC, Camalli M, Cascarano G, Giacovazzo C, Guagliardi A, Moliterni AGG, Polidori G, Spagna R (1999) SIR97: a new tool for crystal structure determination and refinement. J Appl Cryst 32:115–119. doi:10.1107/S0021889898007717

    Article  CAS  Google Scholar 

  47. Sheldrick GM (2008) A short history of SHELX. Acta Cryst A64:112–122. doi:10.1107/S0108767307043930

    Article  Google Scholar 

  48. Farrugia LJ (1999) WinGX suite for small-molecule single-crystal crystallography. J Appl Cryst 32:837–838. doi:10.1107/S0021889899006020

    Article  CAS  Google Scholar 

  49. van der Sluis P, Spek AL (1990) BYPASS: an effective method for the refinement of crystal structures containing disordered solvent regions. Acta Cryst A46:194–201. doi:10.1107/S0108767389011189

    Article  Google Scholar 

  50. Spek AL (2003) Single-crystal structure validation with the program PLATON. J Appl Cryst 36:7–13. doi:10.107/S0021889802022112

    Article  CAS  Google Scholar 

  51. Leclerc S, Garnier M, Hoessel R, Marko D, Bibb JA, Snyder GL, Greengard P, Biernat J, Mandelkow E-M, Eisenbrand G, Meijer L (2001) Indirubins inhibit glycogen synthase kinase-3\(\beta \) and CDK5/P25, two protein kinases involved in abnormal tau phosphorylation in Alzheimer’s disease: a property common to most cyclin-dependant kinase inhibitors? J Biol Chem 276:251–260. doi: 10.1074/jbc.M002466200

    Article  CAS  PubMed  Google Scholar 

  52. Primot A, Baratte B, Gompel M, Borgne A, Liabeuf S, Romette JL, Costantini F, Meijer L (2000) Purification of GSK-3 by affinity chromatography on immobilized axin. Protein Expr Purif 20:394–404. doi:10.1006/prep.2000.1321

    Article  CAS  PubMed  Google Scholar 

  53. Reinhardt J, Ferandin Y, Meijer L (2007) Purification of CK1 by affinity chromatography on immobilised axin. Protein Expr Purif 54:101–109. doi:10.1016/j.pep.2007.02.020

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

One of us (S.G.) wishes to thank the “Ministère de la Recherche et de l’Enseignement Supérieur” for research fellowships. Financial support of this program carried out under the French National Cancer Institute “Cancéropôle Grand Ouest” by contracts PRIR 04-8390 and ACI 04-2254, is gratefully acknowledged.

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Correspondence to Jean-Pierre Bazureau.

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Guiheneuf, S., Paquin, L., Carreaux, F. et al. New 5-ylidene rhodanine derivatives based on the dispacamide A model. Mol Divers 18, 375–388 (2014). https://doi.org/10.1007/s11030-014-9509-7

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