Research Article
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Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold

Year 2024, Volume: 14 Issue: 1, 326 - 332, 01.03.2024

Abdullah Biçer

https://doi.org/10.21597/jist.1339475

Abstract

2,3-disubstituted acrylonitriles derivatives are among the most important molecules in medicinal chemistry due to their bioactivity and their role as starting compounds for many bioactive molecules. Many heterocyclic structures have been investigated as AChE enzyme inhibitors. Nowadays, E/Z acrylonitrile derivatives are being studied as new AChE inhibitors. This study aimed to synthesis new heteroaryl-acrylonitrile compounds using Knoevenagel condensation. In this context, acrylonitrile compounds with aryl and heteroaryl structures at positions 2 and 3 (respectively )were synthesized from the reactions of pyrazole aldehyde derivative (4) with various acetonitrile compounds. Synthesized novel heteroarylacrylonitrile derivatives (5a-d) containing pyrazole ring are potential AChE inhibitors. The structures of the synthesized compounds were elucidated by FTIR, 1H-NMR and 13C-NMR spectroscopic techniques.

Keywords

Arylacrylonitrile Knoevenagel Pyrazole AChE İnhibitors

Thanks

I would like to thank Akdeniz University and Atatürk University Chemistry Departments for spectroscopic measurements.

References

  • Abu-Hashem, A. A., Gouda, M. A., & Badria, F. A. (2010). Synthesis of some new pyrimido[2’,1’:2,3]thiazolo[4,5-b]quinoxaline derivatives as anti-inflammatory and analgesic agents. European Journal of Medicinal Chemistry, 45(5), 1976-1981. https://doi.org/10.1016/J.EJMECH.2010.01.042
  • Anas, S. (2022). Synthesis and biological activity studies of some 3-aryl-2-(4-(substituted phenyl)thiazol-2-yl)acrylonitrile derivatives, Hacettepe Üniversitesi, Sağlık Bilimleri Enstitüsü, Farmasötik Kimya Ana Bilim Dalı, Yüksek lisans Tezi, Ankara.
  • Biçer, A., & Altundaş, R. (2023). Formylation reactions of N-protecting 2-Amino-4-phenyl thiazole compounds. Journal of Molecular Structure, 1289, 135840. https://doi.org/10.1016/J.MOLSTRUC.2023.135840
  • Biçer, A., Cin, G., & Yakalı, G. (2022). Prediction of the Charge Transport and Electronic Properties of Two Pyrazole Derivatives in terms of Their Solid Molecular Arrangements and Reorganization Energy: The Effects of Nitro Groups on Structure-Property Relationship. Authorea. September 27, 2022. https://doi.org/10.22541/au.166425484.40387842/v1
  • De La Torre, P., Saavedra, L. A., Caballero, J., Quiroga, J., Alzate-Morales, J. H., Cabrera, M. G., & Trilleras, J. (2012a). A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles. Molecules 2012, Vol. 17, Pages 12072-12085, 17(10), 12072–12085. https://doi.org/10.3390/MOLECULES171012072
  • De La Torre, P., Saavedra, L. A., Caballero, J., Quiroga, J., Alzate-Morales, J. H., Cabrera, M. G., & Trilleras, J. (2012b). A novel class of selective acetylcholinesterase inhibitors: Synthesis and evaluation of (E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles. Molecules, 17(10), 12072-12085. https://doi.org/10.3390/MOLECULES171012072
  • De-La-Torre, P., Treuer, A. V., Gutierrez, M., Poblete, H., Alzate-Morales, J. H., Trilleras, J., Astudillo-Saavedra, L., & Caballero, J. (2016). Synthesis and in silico analysis of the quantitative structure–activity relationship of heteroaryl–acrylonitriles as AChE inhibitors. Journal of the Taiwan Institute of Chemical Engineers, 59, 45-60. https://doi.org/10.1016/J.JTICE.2015.07.022
  • Fringuelli, F., Pani, G., Piermatti, O., & Pizzo, F. (1994). Condensation reactions in water of active methylene compounds with arylaldehydes. One-pot synthesis of flavonols. Tetrahedron, 50(39), 11499-11508. https://doi.org/10.1016/S0040-4020(01)89287-5
  • Genin, M. J., Biles, C., Keiser, B. J., Poppe, S. M., Swaney, S. M., Tarpley, W. G., Yagi, Y., & Romero, D. L. (2000). Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: Lead identification and SAR of 3- and 4-substituted derivatives. Journal of Medicinal Chemistry, 43(5), 1034-1040. https://doi.org/10.1021/JM990383F/ASSET/IMAGES/MEDIUM/JM990383FN00001.GIF
  • Girisha, K. S., Kalluraya, B., Narayana, V., & Padmashree. (2010). Synthesis and pharmacological study of 1-acetyl/propyl-3-aryl-5-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-2-pyrazoline. European Journal of Medicinal Chemistry, 45(10), 4640-4644. https://doi.org/10.1016/J.EJMECH.2010.07.032
  • Gómez, R., Segura, J. L., & Martín, N. (1999). New optically active polyarylene vinylenes: control of chromophore separation by binaphthyl units. Chemical Communications, 7, 619-620. https://doi.org/10.1039/A809405E
  • Katritzky, A. R., Wang, M., Zhang, S., Voronkov, M. V., & Steel, P. J. (2001). Regioselective synthesis of polysubstituted pyrazoles and isoxazoles. The Journal of Organic Chemistry, 66(20), 6787-6791. https://doi.org/10.1021/JO0101407
  • Kwon, H., Lee, K., & Kim, H. J. (2011). Coumarin–malonitrile conjugate as a fluorescence turn-on probe for biothiols and its cellular expression. Chemical Communications, 47(6), 1773-1775. https://doi.org/10.1039/C0CC04092D
  • Maruyama, S., Tao, X. T., Hokari, H., Noh, T., Zhang, Y., Wada, T., Sasabe, H., Suzuki, H., Watanabe, T., & Miyata, S. (1999). Electroluminescent applications of a cyclic carbazole oligomer. Journal of Materials Chemistry, 9(4), 893-898. https://doi.org/10.1039/A809313J
  • Mukherjee, P. K., Kumar, V., Mal, M., & Houghton, P. J. (2007). Acetylcholinesterase inhibitors from plants. Phytomedicine, 14(4), 289-300. https://doi.org/10.1016/J.PHYMED.2007.02.002
  • Özen, F., Tekin, S., Koran, K., Sandal, S., & Görgülü, A. O. (2016a). Synthesis of 2-(2,3,4-trimethoxyphenyl)-1-(substituted-phenyl)acrylonitriles: in vitro anticancer activity against MCF-7, PC-3 and A2780 cancer cell lines. Research on Chemical Intermediates, 42(12), 7793-7805. https://doi.org/10.1007/S11164-016-2562-3/TABLES/1
  • Özen, F., Tekin, S., Koran, K., Sandal, S., & Görgülü, A. O. (2016b). Synthesis, structural characterization, and in vitro anti-cancer activities of new phenylacrylonitrile derivatives. Applied Biological Chemistry, 59(2), 239–248. https://doi.org/10.1007/S13765-016-0163-X/TABLES/1
  • Parveen, M., Malla, A. M., Alam, M., Ahmad, M., & Rafiq, S. (2014). Stereoselective synthesis of Z-acrylonitrile derivatives: catalytic and acetylcholinesterase inhibition studies. New Journal of Chemistry, 38(4), 1655-1667. https://doi.org/10.1039/C3NJ01384G
  • Parveen, M., Aslam, A., Nami, S. A., & Ahmad, M. (2019). Z-Acrylonitrile Derivatives: Improved Synthesis, X-ray Structure, and Interaction with Human Serum Albumin. Current Organic Synthesis, 16(8), 1149-1160. https://doi.org/10.2174/1570179416666191008085806
  • Sanz, N., Baldeck, P. L., Nicoud, J. F., Le Fur, Y., & Ibanez, A. (2001). Polymorphism and luminescence properties of CMONS organic crystals: bulk crystals and nanocrystals confined in gel-glasses. Solid State Sciences, 3(8), 867-875. https://doi.org/10.1016/S1293-2558(01)01192-X
  • Schulz, V. (2003). Ginkgo extract or cholinesterase inhibitors in patients with dementia: What clinical trials and guidelines fail to consider. Phytomedicine, 10(SUPPL. 4), 74-79. https://doi.org/10.1078/1433-187X-00302
  • Siddiqui, Z. N., Mohammed Musthafa, T. N., Ahmad, A., & Khan, A. U. (2011). Thermal solvent-free synthesis of novel pyrazolyl chalcones and pyrazolines as potential antimicrobial agents. Bioorganic & medicinal chemistry letters, 21(10), 2860-2865. https://doi.org/10.1016/j.bmcl.2011.03.080
  • Siddiqui, Z. N., & Khan, T. (2013). P2O5/SiO2 as an efficient heterogeneous catalyst for the synthesis of heterocyclic alkene derivatives under thermal solvent-free conditions. Catalysis Science & Technology, 3(8), 2032-2043. https://doi.org/10.1039/C3CY00095H
  • Takla, F.N., Farahat, A.A., El-Sayed, M.A.-A. and Nasr, M.N.A. (2017) Molecular Modeling and Synthesis of New Heterocyclic Compounds Containing Pyrazole as Anticancer Drugs. International Journal of Organic Chemistry, 7, 369-388. https://doi.org/10.4236/ijoc.2017.74030
  • Unsal Tan, O., & Zengin, M. (2022). Insights into the chemistry and therapeutic potential of acrylonitrile derivatives. Archiv Der Pharmazie, 355(3). https://doi.org/10.1002/ARDP.202100383
  • Xavier, M., Kornicka, A., Gzella, K., Garbacz, K., Jarosiewicz, M., Gdaniec, M., Fedorowicz, J., Balewski, Ł., Kokoszka, J., & Ordyszewska, A. (2023). Indole-Acrylonitrile Derivatives as Potential Antitumor and Antimicrobial Agents—Synthesis, In Vitro and In Silico Studies. Pharmaceuticals 2023, Vol. 16, Page 918, 16(7), 918. https://doi.org/10.3390/PH16070918

Year 2024, Volume: 14 Issue: 1, 326 - 332, 01.03.2024

Abdullah Biçer

https://doi.org/10.21597/jist.1339475

Abstract

References

  • Abu-Hashem, A. A., Gouda, M. A., & Badria, F. A. (2010). Synthesis of some new pyrimido[2’,1’:2,3]thiazolo[4,5-b]quinoxaline derivatives as anti-inflammatory and analgesic agents. European Journal of Medicinal Chemistry, 45(5), 1976-1981. https://doi.org/10.1016/J.EJMECH.2010.01.042
  • Anas, S. (2022). Synthesis and biological activity studies of some 3-aryl-2-(4-(substituted phenyl)thiazol-2-yl)acrylonitrile derivatives, Hacettepe Üniversitesi, Sağlık Bilimleri Enstitüsü, Farmasötik Kimya Ana Bilim Dalı, Yüksek lisans Tezi, Ankara.
  • Biçer, A., & Altundaş, R. (2023). Formylation reactions of N-protecting 2-Amino-4-phenyl thiazole compounds. Journal of Molecular Structure, 1289, 135840. https://doi.org/10.1016/J.MOLSTRUC.2023.135840
  • Biçer, A., Cin, G., & Yakalı, G. (2022). Prediction of the Charge Transport and Electronic Properties of Two Pyrazole Derivatives in terms of Their Solid Molecular Arrangements and Reorganization Energy: The Effects of Nitro Groups on Structure-Property Relationship. Authorea. September 27, 2022. https://doi.org/10.22541/au.166425484.40387842/v1
  • De La Torre, P., Saavedra, L. A., Caballero, J., Quiroga, J., Alzate-Morales, J. H., Cabrera, M. G., & Trilleras, J. (2012a). A Novel Class of Selective Acetylcholinesterase Inhibitors: Synthesis and Evaluation of (E)-2-(Benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles. Molecules 2012, Vol. 17, Pages 12072-12085, 17(10), 12072–12085. https://doi.org/10.3390/MOLECULES171012072
  • De La Torre, P., Saavedra, L. A., Caballero, J., Quiroga, J., Alzate-Morales, J. H., Cabrera, M. G., & Trilleras, J. (2012b). A novel class of selective acetylcholinesterase inhibitors: Synthesis and evaluation of (E)-2-(benzo[d]thiazol-2-yl)-3-heteroarylacrylonitriles. Molecules, 17(10), 12072-12085. https://doi.org/10.3390/MOLECULES171012072
  • De-La-Torre, P., Treuer, A. V., Gutierrez, M., Poblete, H., Alzate-Morales, J. H., Trilleras, J., Astudillo-Saavedra, L., & Caballero, J. (2016). Synthesis and in silico analysis of the quantitative structure–activity relationship of heteroaryl–acrylonitriles as AChE inhibitors. Journal of the Taiwan Institute of Chemical Engineers, 59, 45-60. https://doi.org/10.1016/J.JTICE.2015.07.022
  • Fringuelli, F., Pani, G., Piermatti, O., & Pizzo, F. (1994). Condensation reactions in water of active methylene compounds with arylaldehydes. One-pot synthesis of flavonols. Tetrahedron, 50(39), 11499-11508. https://doi.org/10.1016/S0040-4020(01)89287-5
  • Genin, M. J., Biles, C., Keiser, B. J., Poppe, S. M., Swaney, S. M., Tarpley, W. G., Yagi, Y., & Romero, D. L. (2000). Novel 1,5-diphenylpyrazole nonnucleoside HIV-1 reverse transcriptase inhibitors with enhanced activity versus the delavirdine-resistant P236L mutant: Lead identification and SAR of 3- and 4-substituted derivatives. Journal of Medicinal Chemistry, 43(5), 1034-1040. https://doi.org/10.1021/JM990383F/ASSET/IMAGES/MEDIUM/JM990383FN00001.GIF
  • Girisha, K. S., Kalluraya, B., Narayana, V., & Padmashree. (2010). Synthesis and pharmacological study of 1-acetyl/propyl-3-aryl-5-(5-chloro-3-methyl-1-phenyl-1H-pyrazol-4-yl)-2-pyrazoline. European Journal of Medicinal Chemistry, 45(10), 4640-4644. https://doi.org/10.1016/J.EJMECH.2010.07.032
  • Gómez, R., Segura, J. L., & Martín, N. (1999). New optically active polyarylene vinylenes: control of chromophore separation by binaphthyl units. Chemical Communications, 7, 619-620. https://doi.org/10.1039/A809405E
  • Katritzky, A. R., Wang, M., Zhang, S., Voronkov, M. V., & Steel, P. J. (2001). Regioselective synthesis of polysubstituted pyrazoles and isoxazoles. The Journal of Organic Chemistry, 66(20), 6787-6791. https://doi.org/10.1021/JO0101407
  • Kwon, H., Lee, K., & Kim, H. J. (2011). Coumarin–malonitrile conjugate as a fluorescence turn-on probe for biothiols and its cellular expression. Chemical Communications, 47(6), 1773-1775. https://doi.org/10.1039/C0CC04092D
  • Maruyama, S., Tao, X. T., Hokari, H., Noh, T., Zhang, Y., Wada, T., Sasabe, H., Suzuki, H., Watanabe, T., & Miyata, S. (1999). Electroluminescent applications of a cyclic carbazole oligomer. Journal of Materials Chemistry, 9(4), 893-898. https://doi.org/10.1039/A809313J
  • Mukherjee, P. K., Kumar, V., Mal, M., & Houghton, P. J. (2007). Acetylcholinesterase inhibitors from plants. Phytomedicine, 14(4), 289-300. https://doi.org/10.1016/J.PHYMED.2007.02.002
  • Özen, F., Tekin, S., Koran, K., Sandal, S., & Görgülü, A. O. (2016a). Synthesis of 2-(2,3,4-trimethoxyphenyl)-1-(substituted-phenyl)acrylonitriles: in vitro anticancer activity against MCF-7, PC-3 and A2780 cancer cell lines. Research on Chemical Intermediates, 42(12), 7793-7805. https://doi.org/10.1007/S11164-016-2562-3/TABLES/1
  • Özen, F., Tekin, S., Koran, K., Sandal, S., & Görgülü, A. O. (2016b). Synthesis, structural characterization, and in vitro anti-cancer activities of new phenylacrylonitrile derivatives. Applied Biological Chemistry, 59(2), 239–248. https://doi.org/10.1007/S13765-016-0163-X/TABLES/1
  • Parveen, M., Malla, A. M., Alam, M., Ahmad, M., & Rafiq, S. (2014). Stereoselective synthesis of Z-acrylonitrile derivatives: catalytic and acetylcholinesterase inhibition studies. New Journal of Chemistry, 38(4), 1655-1667. https://doi.org/10.1039/C3NJ01384G
  • Parveen, M., Aslam, A., Nami, S. A., & Ahmad, M. (2019). Z-Acrylonitrile Derivatives: Improved Synthesis, X-ray Structure, and Interaction with Human Serum Albumin. Current Organic Synthesis, 16(8), 1149-1160. https://doi.org/10.2174/1570179416666191008085806
  • Sanz, N., Baldeck, P. L., Nicoud, J. F., Le Fur, Y., & Ibanez, A. (2001). Polymorphism and luminescence properties of CMONS organic crystals: bulk crystals and nanocrystals confined in gel-glasses. Solid State Sciences, 3(8), 867-875. https://doi.org/10.1016/S1293-2558(01)01192-X
  • Schulz, V. (2003). Ginkgo extract or cholinesterase inhibitors in patients with dementia: What clinical trials and guidelines fail to consider. Phytomedicine, 10(SUPPL. 4), 74-79. https://doi.org/10.1078/1433-187X-00302
  • Siddiqui, Z. N., Mohammed Musthafa, T. N., Ahmad, A., & Khan, A. U. (2011). Thermal solvent-free synthesis of novel pyrazolyl chalcones and pyrazolines as potential antimicrobial agents. Bioorganic & medicinal chemistry letters, 21(10), 2860-2865. https://doi.org/10.1016/j.bmcl.2011.03.080
  • Siddiqui, Z. N., & Khan, T. (2013). P2O5/SiO2 as an efficient heterogeneous catalyst for the synthesis of heterocyclic alkene derivatives under thermal solvent-free conditions. Catalysis Science & Technology, 3(8), 2032-2043. https://doi.org/10.1039/C3CY00095H
  • Takla, F.N., Farahat, A.A., El-Sayed, M.A.-A. and Nasr, M.N.A. (2017) Molecular Modeling and Synthesis of New Heterocyclic Compounds Containing Pyrazole as Anticancer Drugs. International Journal of Organic Chemistry, 7, 369-388. https://doi.org/10.4236/ijoc.2017.74030
  • Unsal Tan, O., & Zengin, M. (2022). Insights into the chemistry and therapeutic potential of acrylonitrile derivatives. Archiv Der Pharmazie, 355(3). https://doi.org/10.1002/ARDP.202100383
  • Xavier, M., Kornicka, A., Gzella, K., Garbacz, K., Jarosiewicz, M., Gdaniec, M., Fedorowicz, J., Balewski, Ł., Kokoszka, J., & Ordyszewska, A. (2023). Indole-Acrylonitrile Derivatives as Potential Antitumor and Antimicrobial Agents—Synthesis, In Vitro and In Silico Studies. Pharmaceuticals 2023, Vol. 16, Page 918, 16(7), 918. https://doi.org/10.3390/PH16070918
There are 26 citations in total.

Details

Primary Language English
Subjects Organic Chemical Synthesis
Journal Section Kimya / Chemistry
Authors

Abdullah Biçer 0000-0003-4648-1834

Early Pub Date February 20, 2024
Publication Date March 1, 2024
Submission Date August 8, 2023
Acceptance Date November 1, 2023
Published in Issue Year 2024 Volume: 14 Issue: 1

Cite

APA Biçer, A. (2024). Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold. Journal of the Institute of Science and Technology, 14(1), 326-332. https://doi.org/10.21597/jist.1339475
AMA Biçer A. Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold. J. Inst. Sci. and Tech. March 2024;14(1):326-332. doi:10.21597/jist.1339475
Chicago Biçer, Abdullah. “Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold”. Journal of the Institute of Science and Technology 14, no. 1 (March 2024): 326-32. https://doi.org/10.21597/jist.1339475.
EndNote Biçer A (March 1, 2024) Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold. Journal of the Institute of Science and Technology 14 1 326–332.
IEEE A. Biçer, “Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold”, J. Inst. Sci. and Tech., vol. 14, no. 1, pp. 326–332, 2024, doi: 10.21597/jist.1339475.
ISNAD Biçer, Abdullah. “Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold”. Journal of the Institute of Science and Technology 14/1 (March 2024), 326-332. https://doi.org/10.21597/jist.1339475.
JAMA Biçer A. Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold. J. Inst. Sci. and Tech. 2024;14:326–332.
MLA Biçer, Abdullah. “Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold”. Journal of the Institute of Science and Technology, vol. 14, no. 1, 2024, pp. 326-32, doi:10.21597/jist.1339475.
Vancouver Biçer A. Synthesis and Characterization of Novel Heteroarylacrylonitrile Derivatives Containing Pyrazole Scaffold. J. Inst. Sci. and Tech. 2024;14(1):326-32.
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