Jump to ContentJump to Main Navigation
Show Summary Details
In This Section

Chemical Papers


IMPACT FACTOR 2015: 1.326

SCImago Journal Rank (SJR) 2015: 0.382
Source Normalized Impact per Paper (SNIP) 2015: 0.560
Impact per Publication (IPP) 2015: 1.279

Online
ISSN
1336-9075
See all formats and pricing
In This Section
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:
/ Bilgesu Sucu
  • Department of Chemistry, Yildiz Technical University, Faculty of Science and Arts, Davutpasa Campus, 34220, Esenler, Istanbul, Turkey
  • Email:
/ Nuket Ocal
  • Department of Chemistry, Yildiz Technical University, Faculty of Science and Arts, Davutpasa Campus, 34220, Esenler, Istanbul, Turkey
  • Email:
/ Dieter Kaufmann
  • Institute of Organic Chemistry, University of Technology, Leibnizstr. 6, Clausthal, D-38678, Clausthal-Zellerfeld, Germany
  • Email:
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)02698-1 [Crossref]

  • [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.200790244 [Web of Science] [Crossref]

  • [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/cr9903048 [Crossref]

  • [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.200800388 [Crossref] [Web of Science]

  • [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.

  • [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.2008.02.171 [Web of Science] [Crossref]

  • [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/molecules15031303 [Web of Science] [Crossref]

  • [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/jm049465g [Crossref]

  • [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/jm0704200 [Crossref]

  • [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.200601423 [Web of Science] [Crossref]

  • [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)00673-7 [Crossref]

  • [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)01144-2 [Crossref]

  • [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/molecules13081570 [Web of Science] [Crossref]

  • [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.2009.04.028 [Web of Science] [Crossref]

  • [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.201100140 [Web of Science] [Crossref]

  • [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. [Crossref]

  • [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/S1070363209020212 [Crossref]

  • [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.

  • [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. [Crossref]

  • [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/molecules15053402 [Web of Science] [Crossref]

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

  • [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.2007.02.010 [Crossref] [Web of Science]

  • [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-X [Crossref]

  • [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.x [Crossref]

  • [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/jm101163m [Crossref]

  • [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.513 [Crossref]

  • [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.2007.05.003 [Web of Science] [Crossref]

  • [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.200902610 [Web of Science] [Crossref]

  • [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/10.3390/11080603 [Crossref]

  • [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)00737-8 [Crossref]

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

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

[1]
Melek Gul, Irem Kulu, Aysegul Peksel, and Nuket Ocal
Journal of Chemistry, 2013, Volume 2013, Page 1

Comments (0)

Please log in or register to comment.
Log in