Main Article Content
Abstract
Chemotherapy against specific molecular targets is one of the most effective approaches used to treat
cancer patients. However, lack of selectivity and development of drug-resistance reduces the efficacy
of cancer chemotherapy. Therefore, development of effective and safe anticancer agents with high
potency and less toxicity is a major focus for researchers across the world. In the current article, the
utility of a reverse ligand similarity based approach to identify potential targets for a new series of
synthesized pyrazole carbothioamides that demonstrate the potent anticancer activities against MCF-
7 cells compared to other structurally related molecules and controls is discussed. Further, in silico
docking analysis provided insights into their sight of binding. Thus, these compounds show promise for
development as next generation anticancer drugs.
Keywords
Annulation
Anticancer
Chemotherapy
Citrus
Pyrazoline
Article Details
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Copyright (c) 2023 Asian Journal of Organic & Medicinal Chemistry
This work is licensed under a Creative Commons Attribution 4.0 International License.
How to Cite
Kumar, A. D. ., Vagish, C. ., Lokeshwari, D. ., Sowmya, R. ., & Kumar, K. A. . (2023). Design, Synthesis, Characterization, Evaluation for Anticancer and Cytotoxic Properties of New Pyrazole Carbothioamides. Asian Journal of Organic & Medicinal Chemistry, 6(1), 53–58. https://doi.org/10.14233/ajomc.2021.AJOMC-P291
References
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1. S. Eckhardt, Recent Progress in the Development of Anticancer Agents, Curr. Med. Chem., 2, 419 (2002); https://doi.org/10.2174/1568011024606389
2. C. Holohan, S. Van Schaeybroeck, D.B. Longley and P.G. Johnston, Cancer Drug Resistance: An Evolving Paradigm, Nat. Rev. Cancer, 13, 714 (2013); https://doi.org/10.1038/nrc3599
3. T. Wang, J. Liu, H. Zhong, H. Chen, Z. Lv, Y. Zhang, M. Zhang, D. Geng, C. Niu, Y. Li and K. Li, Synthesis and Anti-tumor Activity of Novel Ethyl 3-Aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3acarboxylates, Bioorg. Med. Chem. Lett., 21, 3381 (2011); https://doi.org/10.1016/j.bmcl.2011.04.003
4. S. Sangthong, K. Krusong, N. Ngamrojanavanich, T. Vilaivan, S. Puthong, S. Chandchawan and N. Muangsin, Synthesis of Rotenoid Derivatives with Cytotoxic and Topoisomerase II Inhibitory Activities, Bioorg. Med. Chem. Lett., 21, 4813 (2011);
https://doi.org/10.1016/j.bmcl.2011.06.052
5. D. Kralj, M. Friedrich, U. Grošelj, S. Kiraly-Potpara, A. Meden, J. Wagger, G. Dahmann, B. Stanovnik and J. Svete, A Synthesis of 1-Substituted 5-[2-(Acylamino)ethyl]-1H-pyrazole-4-carboxamides, Tetrahedron, 65, 7151 (2009);
https://doi.org/10.1016/j.tet.2009.06.021
6. B.K. Srivastava, R. Soni, J.Z. Patel, A. Joharapurkar, N. Sadhwani, S. Kshirsagar, B. Mishra, V. Takale, S. Gupta, P. Pandya, P. Kapadnis, M. Solanki, H. Patel, P. Mitra, M.R. Jain and P.R. Patel, Hair Growth Stimulator Property of Thienyl Substituted Pyrazole Carboxamide Derivatives as a cb1 Receptor Antagonist with in vivo Antiobesity Effect, Bioorg. Med. Chem. Lett., 19, 2546 (2009); https://doi.org/10.1016/j.bmcl.2009.03.046
7. Y. Xu, X.-H. Liu, M. Saunders, S. Pearce, J.M. Foulks, K.M. Parnell, A. Clifford, R.N. Nix, J. Bullough, T.F. Hendrickson, K. Wright, M.V. McCullar, S.B. Kanner and K.-K. Ho, Discovery of 3-(Trifluoromethyl)-1H-pyrazole-5-carboxamide Activators of the M2 Isoform of Pyruvate Kinase (PKM2), Bioorg. Med. Chem. Lett., 24, 515 (2014); https://doi.org/10.1016/j.bmcl.2013.12.028
8. T. Mohamed, J.C.K. Yeung and P.P.N. Rao, Development of 2-Substituted-N-(naphth-1-ylmethyl) and N-Benzhydrylpyrimidin-4-amines as Dual Cholinesterase and Aβ-aggregation Inhibitors: Synthesis and Biological Evaluation, Bioorg. Med. Chem. Lett., 21, 5881 (2011); https://doi.org/10.1016/j.bmcl.2011.07.091
9. S.-L. Zhu, Y. Wu, C.-J. Liu, C.-Y. Wei, J.-C. Tao and H.-M. Liu, Synthesis and in vitro Cytotoxic Activity Evaluation of Novel Heterocycle Bridged Carbothioamide Type Isosteviol Derivatives as Antitumor Agents, Bioorg. Med. Chem. Lett., 23, 1343 (2013); https://doi.org/10.1016/j.bmcl.2012.12.091
10. J. Zhang, D.-J. Tan, T. Wang, S.-S. Jing, Y. Kang and Z.-T. Zhang, Synthesis, Crystal Structure, Characterization and Antifungal Activity of 3,4-Diaryl-1H-pyrazoles Derivatives, J. Mol. Struct., 1149, 235 (2017);
https://doi.org/10.1016/j.molstruc.2017.07.106
11. Z. Özdemir, H.B. Kandilci, B. Gümüsel, Ü. Calis and A.A. Bilgin, Synthesis and Studies on Antidepressant and Anticonvulsant Activities of Some 3-(2-Furyl)pyrazoline Derivatives, Eur. J. Med. Chem., 42, 373 (2007);
https://doi.org/10.1016/j.ejmech.2006.09.006
12. A.D. Kumar, M.G. Prabhudeva, S. Bharath, K. Kumara, N.K. Lokanath and K.A. Kumar, Design and Amberlyst-15 Mediated Synthesis of Novel Thienyl-pyrazole Carboxamides that Potently Inhibit Phospholipase A2 by Binding to an Allosteric Site on the Enzyme, Bioorg. Chem., 80, 444 (2018); https://doi.org/10.1016/j.bioorg.2018.06.023
13. I.V. Ledenyova, V.V. Didenko, V.V. Dotsenko and K.S. Shikhaliev, Azo-Coupling of Pyrazole-3(5)-diazonium Chlorides with Cyanothioacetamide: A Convenient Synthesis of Pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides, Tetrahedron Lett., 55, 1239 (2014); https://doi.org/10.1016/j.tetlet.2014.01.010
14. N. Renuka, H.K. Vivek, G. Pavithra and K. Ajay Kumar, Synthesis of Coumarin Appended Pyrazolyl-1,3,4-oxadiazoles and Pyrazolyl-1,3,4-thiadiazoles: Evaluation of their in vitro Antimicrobial and Antioxidant Activities and Molecular Docking Studies, Russ. J. Bioorganic Chem., 43, 197 (2017); https://doi.org/10.1134/S106816201702011X
15. E.A. Musad, R. Mohamed, B. Ali Saeed, B.S. Vishwanath and K.M. Lokanatha Rai, Synthesis and Evaluation of Antioxidant and Antibacterial Activities of New Substituted bis(1,3,4-Oxadiazoles), 3,5-bis(substituted) Pyrazoles and Isoxazoles, Bioorg. Med. Chem. Lett., 21, 3536 (2011); https://doi.org/10.1016/j.bmcl.2011.04.142
16. K. Ajay Kumar, K.M. Lokanatha Rai, K.B. Umesha and K.R. Prasad, Synthesis of 3-Aryl-5N-aryl-4,6-dioxopyrrolo-[3,4-d]-7,8-dihydroisoxazolines via 1,3-Dipolar Cycloaddition Reaction, Indian J. Chem., 40B, 269 (2001).
17. H. Wang, X. Sun, S. Zhang, G. Liu, C. Wang, L. Zhu and H. Zhang, Efficient Copper-Catalyzed Synthesis of Substituted Pyrazoles at Room Temperature, Synlett, 29, 2689 (2018); https://doi.org/10.1055/s-0037-1610330
18. M. Tang, Y. Wang, H. Wang and Y. Kong, Aluminum Chloride Mediated Reactions of N-Alkylated Tosylhydrazones and Terminal Alkynes: A Regioselective Approach to 1,3,5-Trisubstituted Pyrazoles, Synthesis, 48, 3065 (2016);
https://doi.org/10.1055/s-0035-1561646
19. V. Lellek, C.-Y. Chen, W. Yang, J. Liu, X. Ji and R. Faessler, An Efficient Synthesis of Substituted Pyrazoles from One-Pot Reaction of Ketones, Aldehydes and Hydrazine Monohydrochloride, Synlett, 29, 1071 (2018); https://doi.org/10.1055/s-0036-1591941
20. F. Yi, W. Zhao, Z. Wang and X. Bi, Silver-Mediated [3 + 2] Cycloaddition of Alkynes and N-Isocyanoiminotriphenylphosphorane: Access to Monosubstituted Pyrazoles, Org. Lett., 21, 3158 (2019); https://doi.org/10.1021/acs.orglett.9b00860
21. D.M. Lokeshwari, D.K. Achutha, B. Srinivasan, N. Shivalingegowda, L.N. Krishnappagowda and A.K. Kariyappa, Synthesis of Novel 2-Pyrazoline analogues with Potent Anti-inflammatory Effect Mediated by Inhibition of Phospholipase A2: Crystallographic, in silico Docking and QSAR Analysis, Bioorg. Med. Chem. Lett., 27, 3806 (2017); https://doi.org/10.1016/j.bmcl.2017.06.063
22. M.G. Prabhudeva, S. Bharath, A.D. Kumar, S. Naveen, N.K. Lokanath, B.N. Mylarappa and K.A. Kumar, Design and Environmentally Benign Synthesis of Novel Thiophene Appended Pyrazole Analogues as Antiinflammatory and Radical scavenging Agents: Crystallographic, in silico Modeling, Docking and SAR Characterization, Bioorg. Chem., 73, 109 (2017); https://doi.org/10.1016/j.bioorg.2017.06.004
23. G. Shan, P. Liu and Y. Rao, A New Synthesis of Pyrazoles through a Lewis Acid Catalyzed Union of 3-Ethoxycyclobutanones with Monosubstituted Hydrazines, Org. Lett., 13, 1746 (2011); https://doi.org/10.1021/ol2002682
24. B.D. Mistry, K.R. Desai, J.A. Patel and N.I. Patel, Conventional and Microwave-Assisted Synthesis of Pyrazole Derivatives and Screening of their Antibacterial and Antifungal Activities, Indian J. Chem., 51B, 746 (2012).
25. M. Rani, M. Yusuf and S.A. Khan, Synthesis and in-vitro Antibacterial Activity of [5-(Furan-2-yl)phenyl]-4,5-carbothioamide Pyrazolines, J. Saudi Chem. Soc., 16, 431 (2012); https://doi.org/10.1016/j.jscs.2011.02.012
26. A. Dileep Kumar, S. Bharath, R.N. Dharmappa, S. Naveen, N.K. Lokanath and K. Ajay Kumar, Design, Synthesis and Spectroscopic and Crystallographic Characterization of Novel Functionalized Pyrazole Derivatives: Biological Evaluation for their Cytotoxic, Angiogenic and Antioxidant Activities, Res. Chem. Intermed., 44, 5635 (2018); https://doi.org/10.1007/s11164-018-3445-6
27. M.S. Christodoulou, S. Liekens, K.M. Kasiotis and S.A. Haroutounian, Novel Pyrazole Derivatives: Synthesis and Evaluation of Anti-Angiogenic Activity, Bioorg. Med. Chem., 18, 4338 (2010); https://doi.org/10.1016/j.bmc.2010.04.076
References
1. S. Eckhardt, Recent Progress in the Development of Anticancer Agents, Curr. Med. Chem., 2, 419 (2002); https://doi.org/10.2174/1568011024606389
2. C. Holohan, S. Van Schaeybroeck, D.B. Longley and P.G. Johnston, Cancer Drug Resistance: An Evolving Paradigm, Nat. Rev. Cancer, 13, 714 (2013); https://doi.org/10.1038/nrc3599
3. T. Wang, J. Liu, H. Zhong, H. Chen, Z. Lv, Y. Zhang, M. Zhang, D. Geng, C. Niu, Y. Li and K. Li, Synthesis and Anti-tumor Activity of Novel Ethyl 3-Aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3acarboxylates, Bioorg. Med. Chem. Lett., 21, 3381 (2011); https://doi.org/10.1016/j.bmcl.2011.04.003
4. S. Sangthong, K. Krusong, N. Ngamrojanavanich, T. Vilaivan, S. Puthong, S. Chandchawan and N. Muangsin, Synthesis of Rotenoid Derivatives with Cytotoxic and Topoisomerase II Inhibitory Activities, Bioorg. Med. Chem. Lett., 21, 4813 (2011);
https://doi.org/10.1016/j.bmcl.2011.06.052
5. D. Kralj, M. Friedrich, U. Grošelj, S. Kiraly-Potpara, A. Meden, J. Wagger, G. Dahmann, B. Stanovnik and J. Svete, A Synthesis of 1-Substituted 5-[2-(Acylamino)ethyl]-1H-pyrazole-4-carboxamides, Tetrahedron, 65, 7151 (2009);
https://doi.org/10.1016/j.tet.2009.06.021
6. B.K. Srivastava, R. Soni, J.Z. Patel, A. Joharapurkar, N. Sadhwani, S. Kshirsagar, B. Mishra, V. Takale, S. Gupta, P. Pandya, P. Kapadnis, M. Solanki, H. Patel, P. Mitra, M.R. Jain and P.R. Patel, Hair Growth Stimulator Property of Thienyl Substituted Pyrazole Carboxamide Derivatives as a cb1 Receptor Antagonist with in vivo Antiobesity Effect, Bioorg. Med. Chem. Lett., 19, 2546 (2009); https://doi.org/10.1016/j.bmcl.2009.03.046
7. Y. Xu, X.-H. Liu, M. Saunders, S. Pearce, J.M. Foulks, K.M. Parnell, A. Clifford, R.N. Nix, J. Bullough, T.F. Hendrickson, K. Wright, M.V. McCullar, S.B. Kanner and K.-K. Ho, Discovery of 3-(Trifluoromethyl)-1H-pyrazole-5-carboxamide Activators of the M2 Isoform of Pyruvate Kinase (PKM2), Bioorg. Med. Chem. Lett., 24, 515 (2014); https://doi.org/10.1016/j.bmcl.2013.12.028
8. T. Mohamed, J.C.K. Yeung and P.P.N. Rao, Development of 2-Substituted-N-(naphth-1-ylmethyl) and N-Benzhydrylpyrimidin-4-amines as Dual Cholinesterase and Aβ-aggregation Inhibitors: Synthesis and Biological Evaluation, Bioorg. Med. Chem. Lett., 21, 5881 (2011); https://doi.org/10.1016/j.bmcl.2011.07.091
9. S.-L. Zhu, Y. Wu, C.-J. Liu, C.-Y. Wei, J.-C. Tao and H.-M. Liu, Synthesis and in vitro Cytotoxic Activity Evaluation of Novel Heterocycle Bridged Carbothioamide Type Isosteviol Derivatives as Antitumor Agents, Bioorg. Med. Chem. Lett., 23, 1343 (2013); https://doi.org/10.1016/j.bmcl.2012.12.091
10. J. Zhang, D.-J. Tan, T. Wang, S.-S. Jing, Y. Kang and Z.-T. Zhang, Synthesis, Crystal Structure, Characterization and Antifungal Activity of 3,4-Diaryl-1H-pyrazoles Derivatives, J. Mol. Struct., 1149, 235 (2017);
https://doi.org/10.1016/j.molstruc.2017.07.106
11. Z. Özdemir, H.B. Kandilci, B. Gümüsel, Ü. Calis and A.A. Bilgin, Synthesis and Studies on Antidepressant and Anticonvulsant Activities of Some 3-(2-Furyl)pyrazoline Derivatives, Eur. J. Med. Chem., 42, 373 (2007);
https://doi.org/10.1016/j.ejmech.2006.09.006
12. A.D. Kumar, M.G. Prabhudeva, S. Bharath, K. Kumara, N.K. Lokanath and K.A. Kumar, Design and Amberlyst-15 Mediated Synthesis of Novel Thienyl-pyrazole Carboxamides that Potently Inhibit Phospholipase A2 by Binding to an Allosteric Site on the Enzyme, Bioorg. Chem., 80, 444 (2018); https://doi.org/10.1016/j.bioorg.2018.06.023
13. I.V. Ledenyova, V.V. Didenko, V.V. Dotsenko and K.S. Shikhaliev, Azo-Coupling of Pyrazole-3(5)-diazonium Chlorides with Cyanothioacetamide: A Convenient Synthesis of Pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides, Tetrahedron Lett., 55, 1239 (2014); https://doi.org/10.1016/j.tetlet.2014.01.010
14. N. Renuka, H.K. Vivek, G. Pavithra and K. Ajay Kumar, Synthesis of Coumarin Appended Pyrazolyl-1,3,4-oxadiazoles and Pyrazolyl-1,3,4-thiadiazoles: Evaluation of their in vitro Antimicrobial and Antioxidant Activities and Molecular Docking Studies, Russ. J. Bioorganic Chem., 43, 197 (2017); https://doi.org/10.1134/S106816201702011X
15. E.A. Musad, R. Mohamed, B. Ali Saeed, B.S. Vishwanath and K.M. Lokanatha Rai, Synthesis and Evaluation of Antioxidant and Antibacterial Activities of New Substituted bis(1,3,4-Oxadiazoles), 3,5-bis(substituted) Pyrazoles and Isoxazoles, Bioorg. Med. Chem. Lett., 21, 3536 (2011); https://doi.org/10.1016/j.bmcl.2011.04.142
16. K. Ajay Kumar, K.M. Lokanatha Rai, K.B. Umesha and K.R. Prasad, Synthesis of 3-Aryl-5N-aryl-4,6-dioxopyrrolo-[3,4-d]-7,8-dihydroisoxazolines via 1,3-Dipolar Cycloaddition Reaction, Indian J. Chem., 40B, 269 (2001).
17. H. Wang, X. Sun, S. Zhang, G. Liu, C. Wang, L. Zhu and H. Zhang, Efficient Copper-Catalyzed Synthesis of Substituted Pyrazoles at Room Temperature, Synlett, 29, 2689 (2018); https://doi.org/10.1055/s-0037-1610330
18. M. Tang, Y. Wang, H. Wang and Y. Kong, Aluminum Chloride Mediated Reactions of N-Alkylated Tosylhydrazones and Terminal Alkynes: A Regioselective Approach to 1,3,5-Trisubstituted Pyrazoles, Synthesis, 48, 3065 (2016);
https://doi.org/10.1055/s-0035-1561646
19. V. Lellek, C.-Y. Chen, W. Yang, J. Liu, X. Ji and R. Faessler, An Efficient Synthesis of Substituted Pyrazoles from One-Pot Reaction of Ketones, Aldehydes and Hydrazine Monohydrochloride, Synlett, 29, 1071 (2018); https://doi.org/10.1055/s-0036-1591941
20. F. Yi, W. Zhao, Z. Wang and X. Bi, Silver-Mediated [3 + 2] Cycloaddition of Alkynes and N-Isocyanoiminotriphenylphosphorane: Access to Monosubstituted Pyrazoles, Org. Lett., 21, 3158 (2019); https://doi.org/10.1021/acs.orglett.9b00860
21. D.M. Lokeshwari, D.K. Achutha, B. Srinivasan, N. Shivalingegowda, L.N. Krishnappagowda and A.K. Kariyappa, Synthesis of Novel 2-Pyrazoline analogues with Potent Anti-inflammatory Effect Mediated by Inhibition of Phospholipase A2: Crystallographic, in silico Docking and QSAR Analysis, Bioorg. Med. Chem. Lett., 27, 3806 (2017); https://doi.org/10.1016/j.bmcl.2017.06.063
22. M.G. Prabhudeva, S. Bharath, A.D. Kumar, S. Naveen, N.K. Lokanath, B.N. Mylarappa and K.A. Kumar, Design and Environmentally Benign Synthesis of Novel Thiophene Appended Pyrazole Analogues as Antiinflammatory and Radical scavenging Agents: Crystallographic, in silico Modeling, Docking and SAR Characterization, Bioorg. Chem., 73, 109 (2017); https://doi.org/10.1016/j.bioorg.2017.06.004
23. G. Shan, P. Liu and Y. Rao, A New Synthesis of Pyrazoles through a Lewis Acid Catalyzed Union of 3-Ethoxycyclobutanones with Monosubstituted Hydrazines, Org. Lett., 13, 1746 (2011); https://doi.org/10.1021/ol2002682
24. B.D. Mistry, K.R. Desai, J.A. Patel and N.I. Patel, Conventional and Microwave-Assisted Synthesis of Pyrazole Derivatives and Screening of their Antibacterial and Antifungal Activities, Indian J. Chem., 51B, 746 (2012).
25. M. Rani, M. Yusuf and S.A. Khan, Synthesis and in-vitro Antibacterial Activity of [5-(Furan-2-yl)phenyl]-4,5-carbothioamide Pyrazolines, J. Saudi Chem. Soc., 16, 431 (2012); https://doi.org/10.1016/j.jscs.2011.02.012
26. A. Dileep Kumar, S. Bharath, R.N. Dharmappa, S. Naveen, N.K. Lokanath and K. Ajay Kumar, Design, Synthesis and Spectroscopic and Crystallographic Characterization of Novel Functionalized Pyrazole Derivatives: Biological Evaluation for their Cytotoxic, Angiogenic and Antioxidant Activities, Res. Chem. Intermed., 44, 5635 (2018); https://doi.org/10.1007/s11164-018-3445-6
27. M.S. Christodoulou, S. Liekens, K.M. Kasiotis and S.A. Haroutounian, Novel Pyrazole Derivatives: Synthesis and Evaluation of Anti-Angiogenic Activity, Bioorg. Med. Chem., 18, 4338 (2010); https://doi.org/10.1016/j.bmc.2010.04.076
2. C. Holohan, S. Van Schaeybroeck, D.B. Longley and P.G. Johnston, Cancer Drug Resistance: An Evolving Paradigm, Nat. Rev. Cancer, 13, 714 (2013); https://doi.org/10.1038/nrc3599
3. T. Wang, J. Liu, H. Zhong, H. Chen, Z. Lv, Y. Zhang, M. Zhang, D. Geng, C. Niu, Y. Li and K. Li, Synthesis and Anti-tumor Activity of Novel Ethyl 3-Aryl-4-oxo-3,3a,4,6-tetrahydro-1H-furo[3,4-c]pyran-3acarboxylates, Bioorg. Med. Chem. Lett., 21, 3381 (2011); https://doi.org/10.1016/j.bmcl.2011.04.003
4. S. Sangthong, K. Krusong, N. Ngamrojanavanich, T. Vilaivan, S. Puthong, S. Chandchawan and N. Muangsin, Synthesis of Rotenoid Derivatives with Cytotoxic and Topoisomerase II Inhibitory Activities, Bioorg. Med. Chem. Lett., 21, 4813 (2011);
https://doi.org/10.1016/j.bmcl.2011.06.052
5. D. Kralj, M. Friedrich, U. Grošelj, S. Kiraly-Potpara, A. Meden, J. Wagger, G. Dahmann, B. Stanovnik and J. Svete, A Synthesis of 1-Substituted 5-[2-(Acylamino)ethyl]-1H-pyrazole-4-carboxamides, Tetrahedron, 65, 7151 (2009);
https://doi.org/10.1016/j.tet.2009.06.021
6. B.K. Srivastava, R. Soni, J.Z. Patel, A. Joharapurkar, N. Sadhwani, S. Kshirsagar, B. Mishra, V. Takale, S. Gupta, P. Pandya, P. Kapadnis, M. Solanki, H. Patel, P. Mitra, M.R. Jain and P.R. Patel, Hair Growth Stimulator Property of Thienyl Substituted Pyrazole Carboxamide Derivatives as a cb1 Receptor Antagonist with in vivo Antiobesity Effect, Bioorg. Med. Chem. Lett., 19, 2546 (2009); https://doi.org/10.1016/j.bmcl.2009.03.046
7. Y. Xu, X.-H. Liu, M. Saunders, S. Pearce, J.M. Foulks, K.M. Parnell, A. Clifford, R.N. Nix, J. Bullough, T.F. Hendrickson, K. Wright, M.V. McCullar, S.B. Kanner and K.-K. Ho, Discovery of 3-(Trifluoromethyl)-1H-pyrazole-5-carboxamide Activators of the M2 Isoform of Pyruvate Kinase (PKM2), Bioorg. Med. Chem. Lett., 24, 515 (2014); https://doi.org/10.1016/j.bmcl.2013.12.028
8. T. Mohamed, J.C.K. Yeung and P.P.N. Rao, Development of 2-Substituted-N-(naphth-1-ylmethyl) and N-Benzhydrylpyrimidin-4-amines as Dual Cholinesterase and Aβ-aggregation Inhibitors: Synthesis and Biological Evaluation, Bioorg. Med. Chem. Lett., 21, 5881 (2011); https://doi.org/10.1016/j.bmcl.2011.07.091
9. S.-L. Zhu, Y. Wu, C.-J. Liu, C.-Y. Wei, J.-C. Tao and H.-M. Liu, Synthesis and in vitro Cytotoxic Activity Evaluation of Novel Heterocycle Bridged Carbothioamide Type Isosteviol Derivatives as Antitumor Agents, Bioorg. Med. Chem. Lett., 23, 1343 (2013); https://doi.org/10.1016/j.bmcl.2012.12.091
10. J. Zhang, D.-J. Tan, T. Wang, S.-S. Jing, Y. Kang and Z.-T. Zhang, Synthesis, Crystal Structure, Characterization and Antifungal Activity of 3,4-Diaryl-1H-pyrazoles Derivatives, J. Mol. Struct., 1149, 235 (2017);
https://doi.org/10.1016/j.molstruc.2017.07.106
11. Z. Özdemir, H.B. Kandilci, B. Gümüsel, Ü. Calis and A.A. Bilgin, Synthesis and Studies on Antidepressant and Anticonvulsant Activities of Some 3-(2-Furyl)pyrazoline Derivatives, Eur. J. Med. Chem., 42, 373 (2007);
https://doi.org/10.1016/j.ejmech.2006.09.006
12. A.D. Kumar, M.G. Prabhudeva, S. Bharath, K. Kumara, N.K. Lokanath and K.A. Kumar, Design and Amberlyst-15 Mediated Synthesis of Novel Thienyl-pyrazole Carboxamides that Potently Inhibit Phospholipase A2 by Binding to an Allosteric Site on the Enzyme, Bioorg. Chem., 80, 444 (2018); https://doi.org/10.1016/j.bioorg.2018.06.023
13. I.V. Ledenyova, V.V. Didenko, V.V. Dotsenko and K.S. Shikhaliev, Azo-Coupling of Pyrazole-3(5)-diazonium Chlorides with Cyanothioacetamide: A Convenient Synthesis of Pyrazolo[5,1-c][1,2,4]triazine-3-carbothioamides, Tetrahedron Lett., 55, 1239 (2014); https://doi.org/10.1016/j.tetlet.2014.01.010
14. N. Renuka, H.K. Vivek, G. Pavithra and K. Ajay Kumar, Synthesis of Coumarin Appended Pyrazolyl-1,3,4-oxadiazoles and Pyrazolyl-1,3,4-thiadiazoles: Evaluation of their in vitro Antimicrobial and Antioxidant Activities and Molecular Docking Studies, Russ. J. Bioorganic Chem., 43, 197 (2017); https://doi.org/10.1134/S106816201702011X
15. E.A. Musad, R. Mohamed, B. Ali Saeed, B.S. Vishwanath and K.M. Lokanatha Rai, Synthesis and Evaluation of Antioxidant and Antibacterial Activities of New Substituted bis(1,3,4-Oxadiazoles), 3,5-bis(substituted) Pyrazoles and Isoxazoles, Bioorg. Med. Chem. Lett., 21, 3536 (2011); https://doi.org/10.1016/j.bmcl.2011.04.142
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