Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Chemical Papers


IMPACT FACTOR 2016: 1.258

SCImago Journal Rank (SJR) 2016: 0.348
Source Normalized Impact per Paper (SNIP) 2016: 0.533

Online
ISSN
1336-9075
See all formats and pricing
More options …
Volume 67, Issue 6 (Jun 2013)

Issues

Synthesis of new aryl(hetaryl)-substituted tandospirone analogues with potential anxiolytic activity via reductive Heck type hydroarylations

Omer Gunkara
  • Department of Chemistry, Yildiz Technical University, Faculty of Science and Arts, Davutpasa Campus, 34220, Esenler, Istanbul, Turkey
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Bilgesu Sucu
  • Department of Chemistry, Yildiz Technical University, Faculty of Science and Arts, Davutpasa Campus, 34220, Esenler, Istanbul, Turkey
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Nuket Ocal
  • Department of Chemistry, Yildiz Technical University, Faculty of Science and Arts, Davutpasa Campus, 34220, Esenler, Istanbul, Turkey
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dieter Kaufmann
  • Institute of Organic Chemistry, University of Technology, Leibnizstr. 6, Clausthal, D-38678, Clausthal-Zellerfeld, Germany
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2013-03-16 | DOI: https://doi.org/10.2478/s11696-013-0338-4

Abstract

Tandospirone (I), developed as an anxiolytic drug, is an aryl-piperazine compound that binds to both 5-HT1A and dopamine D4 receptors. Palladium-catalysed hydroarylation reactions of tandospirone analogues containing an oxygen bridge and 3-(trifluoromethyl)phenyl or 2,3-dichlorophenyl groups were studied in order to find a new stereoselective access to a series of new exo-aryl(hetaryl)-substituted derivatives with potential biological activity.

Keywords: tandospirone; arylpiperazines; C-C coupling; hydroarylation; heterocycles

  • [1] Amano, T., Akbar, M., Matsubayashi, H., & Sasa, M. (2001). Inhibitory effects of tandospirone, a 5-HT1A agonist, on medial vestibular nucleus neurons responding to lateral roll tilt stimulation in rats. Brain Research, 910, 195–198. DOI: 10.1016/s0006-8993(01)02698-1. http://dx.doi.org/10.1016/S0006-8993(01)02698-1CrossrefGoogle Scholar

  • [2] Bagdatli, E., Ocal, N., & Kaufmann, D. E. (2007). An investigation into domino-Heck reactions of N-acylaminosubstituted tricyclic imides: Synthesis of new prospective pharmaceuticals. Helvetica Chimica Acta, 90, 2380–2385. DOI: 10.1002/hlca.200790244. http://dx.doi.org/10.1002/hlca.200790244Web of ScienceCrossrefGoogle Scholar

  • [3] Beletskaya, I. P., & Cheprakov, A. V. (2000). The Heck reaction as a sharpening stone of palladium catalysis. Chemical Reviews, 100, 3009–3066. DOI: 10.1021/cr9903048. http://dx.doi.org/10.1021/cr9903048CrossrefGoogle Scholar

  • [4] Celik, C., Kulu, I., Ocal, N., & Kaufmann, D. E. (2009). Domino-Heck reactions of carba- and oxabicyclic, unsaturated dicarboximides: Synthesis of aryl-substituted, bridged perhydroisoindole derivatives. Helvetica Chimica Acta, 92, 1092–1101. DOI: 10.1002/hlca.200800388. http://dx.doi.org/10.1002/hlca.200800388CrossrefWeb of ScienceGoogle Scholar

  • [5] Godfrey, A. G., Kohlman, D. T., O’Toole, J. C., Xu, Y. C., & Zhang, T. Y. (2006). U.S. Patent No. 7001908 B2. Washington, DC, USA: U.S. Patent and Trademark Office. Google Scholar

  • [6] Göksu, G., Gül, M., Öcal, N., & Kaufmann, D. E. (2008). Hydroarylation of bicyclic, unsaturated dicarboximides: access to aryl-substituted, bridged perhydroisoindoles. Tetrahedron Letters, 49, 2685–2688. DOI: 10.1016/j.tetlet.2008.02.171 http://dx.doi.org/10.1016/j.tetlet.2008.02.171Web of ScienceCrossrefGoogle Scholar

  • [7] Goksu, G., Ocal, N., & Kaufmann, D. E. (2010). Reductive Heck reactions of N-methyl-substituted tricyclic imides. Molecules, 15, 1302–1308. DOI: 10.3390/molecules15031303. http://dx.doi.org/10.3390/molecules15031303Web of ScienceCrossrefGoogle Scholar

  • [8] Grundt, P., Carlson, E. E., Cao, J., Bennett, C. J., McElveen, E., Taylor, M., Luedtke, R. R., & Newman, A. H. (2005). Novel heterocyclic trans olefin analogues of N-{4-[4-(2,3-dichlorophenyl)piperazin-1-yl]butyl}arylcarboxamides as selective probes with high affinity for the dopamine D3 receptor. Journal of Medicinal Chemistry, 48, 839–848. DOI: 10.1021/jm049465g. http://dx.doi.org/10.1021/jm049465gCrossrefGoogle Scholar

  • [9] Grundt, P., Prevatt, K. M., Cao, J., Taylor, M., Floresca, C. Z., Choi, J. K., Jenkins, B. G., Luedtke, R. R., & Newman, A. H. (2007). Heterocyclic analogues of N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)arylcarboxamides with functionalized linking chains as novel dopamine D3 receptor ligands: Potential substance abuse therapeutic agents. Journal of Medicinal Chemistry, 50, 4135–4146. DOI: 10.1021/ jm0704200. http://dx.doi.org/10.1021/jm0704200CrossrefGoogle Scholar

  • [10] Ishihara, Y., Bazzi, H. S., Toader, V., Godin, F., & Sleiman, H. F. (2007). Molecule-responsive block copolymer micelles. Chemistry — A European Journal, 13, 4560–4570. DOI: 10.1002/chem.200601423. http://dx.doi.org/10.1002/chem.200601423Web of ScienceCrossrefGoogle Scholar

  • [11] Kishimoto, K., Koyama, S., & Akaike, N. (2000). Presynaptic modulation of synaptic -aminobutyric acid transmission by tandospirone in rat basolateral amygdala. European Journal of Pharmacology, 407, 257–265. DOI: 10.1016/s0014-2999(00)00673-7. http://dx.doi.org/10.1016/S0014-2999(00)00673-7CrossrefGoogle Scholar

  • [12] Kossakowski, J., & Jarocka, M. (2001). Synthesis of new N-substituted cyclic imides with an expected anxiolytic activity. XVII. Derivatives of 1-ethoxybicyclo[2.2.2]-oct-5-one-2,3-dicarboximide. Il Farmaco, 56, 785–789. DOI: 10.1016/s0014-827x(01)01144-2. http://dx.doi.org/10.1016/S0014-827X(01)01144-2CrossrefGoogle Scholar

  • [13] Kossakowski, J., Bielenica, A., Mirosław, B., Koziol, A. E., Dybala, I., & Struga, M. (2008). 4-Azatricyclo[5.2.2.02,6]undecane-3,5,8-triones as potential pharmacological agents. Molecules, 13, 1570–1583. DOI: 10.3390/molecules13081570. http://dx.doi.org/10.3390/molecules13081570Web of ScienceCrossrefGoogle Scholar

  • [14] Kulig, K., Sapa, J., Nowaczyk, A., Filipek, B., & Malawska, B. (2009). Design, synthesis and pharmacological evaluation of new 1-[3-(4-arylpiperazin-1-yl)-2-hydroxy-propyl]-3,3-diphenylpyrrolidin-2-one derivatives with antiarrhythmic, antihypertensive, and α-adrenolytic activity. European Journal of Medicinal Chemistry, 44, 3954–4003. DOI: 10.1016/j.ejmech.2009.04.028. http://dx.doi.org/10.1016/j.ejmech.2009.04.028Web of ScienceCrossrefGoogle Scholar

  • [15] Kulu, I., & Ocal, N. (2011). The synthesis of epiboxidine and related analogues as potential pharmacological agents. Helvetica Chimica Acta, 94, 2054–2060. DOI: 10.1002/hlca.201100140. http://dx.doi.org/10.1002/hlca.201100140Web of ScienceCrossrefGoogle Scholar

  • [16] Kulu, I., Kopruceli, A., Goksu, G., & Ocal, N. (2012) Synthesis of new aryl(hetaryl)-substituted tandospirones under reductive Heck type hydroarylations and isoxazoline derivatives via 1,3-dipolar cycloaddition reactions with expected anxiolytic activity. Current Organic Synthesis. In press. DOI: 10.2174/1570212700121661794. CrossrefGoogle Scholar

  • [17] Makan, S. Y., Tsymbal, D. I., Soboleva, S. G., Tarabara, I. N., Kas’yan, L. I., & Andronati, S. A. (2009). N-[4-(Arylpiperazin-1-yl)butyl]bicyclo[2.2.1]hept-5-ene-endo-2, endo-3-dicarboximides and their epoxy derivatives. Synthesis and affinity for 5-HT1a receptors. Russian Journal of General Chemistry, 79, 292–296. DOI: 10.1134/s1070363209020212. http://dx.doi.org/10.1134/S1070363209020212CrossrefGoogle Scholar

  • [18] Mitchell, D., & Yu, H. (2003). Synthetic applications of palladium-catalyzed hydroarylation and related systems. Current Opinion in Drug Discovery and Development, 6, 876–883. Google Scholar

  • [19] Namyslo, J. C., & Kaufmann, D. E. (1999). Chemistry in the ambient field of the alkaloid epibatidine. Part 2. Triphenylarsine as an efficient ligand in the Pd-catalyzed synthesis of epibatidine and analogs. Synlett, 1999, 114–116. DOI: 10.1055/s-1999-2528. CrossrefGoogle Scholar

  • [20] Namyslo, J. C., Storsberg, J., Klinge, J., Göttner, C., Yao, M. L., Ocal, N., & Kaufmann, D. E. (2010). The hydroarylation reaction—scope and limitations. Molecules, 15, 3402–3410. DOI: 10.3390/molecules15053402. http://dx.doi.org/10.3390/molecules15053402Web of ScienceCrossrefGoogle Scholar

  • [21] Negishi, E. I., & de Meijere, A. (2002). Handbook of organopalladium chemistry for organic synthesis. New York, NY, USA: Wiley. http://dx.doi.org/10.1002/0471473804Google Scholar

  • [22] Nishikawa, H., Inoue, T., Izumi, T., & Koyama, T. (2007). Synergistic effects of tandospirone and selective serotonin reuptake inhibitors on the contextual conditioned fear stress response in rats. European Neuropsychopharmacology, 17, 643–650. DOI: 10.1016/j.euroneuro.2007.02.010. http://dx.doi.org/10.1016/j.euroneuro.2007.02.010CrossrefWeb of ScienceGoogle Scholar

  • [23] Pickard, G. E., & Rea, M. A. (1997). TFMPP, a 5HT1B receptor agonist, inhibits light-induced phase shifts of the circadian activity rhythm and c-Fos expression in the mouse suprachiasmatic nucleus. Neuroscience Letters, 231, 95–98. DOI: 10.1016/s0304-3940(97)00534-x. http://dx.doi.org/10.1016/S0304-3940(97)00534-XCrossrefGoogle Scholar

  • [24] Przegaliński, E., Baran, L., & Siwanowicz, J. (1994). Role of 5-hydroxytryptamine receptor subtypes in the 1-[3-(trifluoromethyl)phenyl]piperazine-induced increase in threshold for maximal electroconvulsions in mice. Epilepsia, 35, 889–894. DOI: 10.1111/j.1528-1157.1994.tb02528.x. http://dx.doi.org/10.1111/j.1528-1157.1994.tb02528.xCrossrefGoogle Scholar

  • [25] Sarswat, A., Kumar, R., Kumar, L., Lal, N., Sharma, S., Prabhakar, Y. S., Pandey, S. K., Lal, J., Verma, V., Jain, A., Maikhuri, J. P., Dalela, D., Gupta, G., & Sharma, V. L. (2011). Arylpiperazines for management of benign prostatic hyperplasia: Design, synthesis, quantitative structure-activity relationships, and pharmacokinetic studies. Journal of Medicinal Chemistry, 54, 302–311. DOI: 10.1021/jm101163m. http://dx.doi.org/10.1021/jm101163mCrossrefGoogle Scholar

  • [26] Staack, R. F., Fritschi, G., & Maurer, H. H. (2003). New designer drug 1-(3-trifluoromethylphenyl) piperazine (TFMPP): gas chromatography/mass spectrometry and liquid chromatography/ mass spectrometry studies on its phase I and II metabolism and on its toxicological detection in rat urine. Journal of Mass Spectrometry, 38, 971–981. DOI: 10.1002/jms.513. http://dx.doi.org/10.1002/jms.513CrossrefGoogle Scholar

  • [27] Takahashi, T., Mitsuya, H., Murata, T., Murayama, J., & Wada, Y. (2008). Opposite effects of SSRIs and tandospirone in the treatment of REM sleep behavior disorder. Sleep Medicine, 9, 317–319. DOI: 10.1016/j.sleep.2007.05.003. http://dx.doi.org/10.1016/j.sleep.2007.05.003Web of ScienceCrossrefGoogle Scholar

  • [28] Tindale, J. J., Hartlen, K. D., Alizadeh, A., Workentin, M. S., & Ragogna, P. J. (2010). Maleimide-modified phosphonium ionic liquids: A template towards (multi)task-specific ionic liquids. Chemistry — A European Journal, 16, 9068–9075. DOI: 10.1002/chem.200902610. http://dx.doi.org/10.1002/chem.200902610Web of ScienceCrossrefGoogle Scholar

  • [29] Yolacan, Ç., Bagdatli, E., Öcal, N., & Kaufmann, D. E. (2006). Epibatidine alkaloid chemistry: 5. Domino-Heck reactions of azabicyclic and tricyclic systems. Molecules, 11, 603–614. DOI: 10.3390/11080603. http://dx.doi.org/10.3390/11080603CrossrefGoogle Scholar

  • [30] Wei, Z. L., George, C., & Kozikowski, A. P. (2003). Synthesis of 5-endo-, 5-exo-, 6-endo- and 6-exo-hydroxylated analogues of epibatidine. Tetrahedron Letters, 44, 3847–3850. DOI: 10.1016/s0040-4039(03)00737-8. http://dx.doi.org/10.1016/S0040-4039(03)00737-8CrossrefGoogle Scholar

About the article

Published Online: 2013-03-16

Published in Print: 2013-06-01


Citation Information: Chemical Papers, ISSN (Online) 1336-9075, DOI: https://doi.org/10.2478/s11696-013-0338-4.

Export Citation

© 2013 Institute of Chemistry, Slovak Academy of Sciences. Copyright Clearance Center

Comments (0)

Please log in or register to comment.
Log in