The Reaction of Cyanoacetylhydrazine with Chloroacetone: Synthesis of 1,2,4-Triazine, 1,3,4-Oxadiazine and Their Fused Derivatives with Antitumor Activities


The reaction of cyanoacetylhydrazine with chloroacetone gave the N-(1-chloropropan-2-ylidene)-2-cyanoacetohy- drazide. This compound reacted with either hydrazine hydrate or phenylhydrazine to give the corresponding 1,2,4-tri- azine derivatives. On the other hand, its reaction with either benzenediazonium chloride or benzaldehyde gave in each case the 1,3,4-oxadiazine derivatives. Moreover, the reaction of the cyanoacetylhydrazine with 2-boromocyclohexa- none gave the corresponding hydrazine-hydrozon derivative. The antitumor evaluation of the newly synthesized prod- ucts against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) was recorded. Some of the tested compounds showed activities which was higher than the reference doxorubicin.

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R. Mohareb and E. Samir, "The Reaction of Cyanoacetylhydrazine with Chloroacetone: Synthesis of 1,2,4-Triazine, 1,3,4-Oxadiazine and Their Fused Derivatives with Antitumor Activities," Open Journal of Medicinal Chemistry, Vol. 2 No. 1, 2012, pp. 1-9. doi: 10.4236/ojmc.2012.21001.

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The authors declare no conflicts of interest.


[1] C. Loncle, J. M. Brunel, N. Vidal, M. Dherbomez and Y. Letourneux, “Synthesis and Antifungal Activity of Cholesterol-Hydrazone Derivatives,” European Journal of Medicinal Chemistry, Vol. 39, No. 12, 2004, pp. 1067-1071. doi:10.1016/j.ejmech.2004.07.005
[2] S. P. Garoufalias, N. Pouli, P. A. Marakos and G. Ladas, “Synthesis Antimicrobial and Antifungal Activity of Some New 3-Substituted Derivatives of 4-(2,4-Dichlorophenyl)5-Adamantyl-1 H-1,2,4-Triazole,” II Farmaco, 2002, Vol. 57, No. 12, pp. 973-977. doi:10.1016/S0014-827X(02)01227-2
[3] P. Vicini, F. Zani, P. Cozzini and I. Doytchinova, “Hydrazones of 1,2-Benzisothiazole Hydrazides: Synthesis, Antimicrobial Activity and QSAR Investigations,” European Journal of Medicinal Chemistry, Vol. 37, No. 7, 2002, pp. 553-564. doi:10.1016/S0223-5234(02)01378-8
[4] F. D. Popp, “Potential Anticonvulsant XII. Anticonvulsant Activity of Some Aldehyd Derivatives,” European Journal of Medicinal Chemistry, Vol. 24, No. 3, 1989, pp. 313-315. doi:10.1016/0223-5234(89)90016-0
[5] S. K. Sridhar, S. N. Pandeya, J. P. Stables and A. Ramesh, “Anti-Convulsant Activity of Hydrazones, Schiff and Mann Basis of Istatin Derivatives,” European Journal of Pharmaceutical Science, Vol. 16, No. 3, 2002, pp. 129-132. doi:1016/S0928-0987(02)00077-5
[6] S. G. Kü?ükgüzel, A. Mazi, F. Sahin, S. ?ztürk and J. P. Stables, “Synthesis and Biological Activities of Diflunisal Hydrazide-Hydrazones,” European Journal of Medicinal Chemistry, Vol. 38, No. 11, 2003, pp. 1005-1013. doi:10.1016/j.ejmech.2003.08.004
[7] M. A. Gaston, L. R. Dias, A. C. Freitas, A. L. Miranda and P. Barreiro, “Synthesis and Analgesic Properties of New 4-Arylhydrazone 1-H Pyrazole [3,4-b] Pyridine Derivatives,” Pharmaceutica Acta Helvetiae, Vol. 71, No. 2, 1996, pp. 213-219. doi:10.1016/0031-6865(96)00012-X
[8] S. Gemma, G. Kukreja, C. Fattorusso, M. Persico, M. Romano, M. Altarelli, L. Savini, G. Campiani, E. Fattorusso and N. Basilico, “Synthesis of N1-Arylidene-N2Quinolyland N2-Acrydinylhydrazones as Potent Antimalarial Agents Active against CQ-Resistant P. falciparumstrains,” Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 20, 2006, pp. 5384-5388. doi:10.1016/j.bmcl.2006.07.060
[9] A. D. Pilla, S. Rani, P. D. Rathod, F. P. Xanvier, K. Vasu, K. H. Padh and V. Sudarsanam, “QSAR Studies on Some Thiophene Analogs as Anti-Inflammatory Agents: Enhancement of Activity by Electronic Parameters and Its Utilization for Chemical Lead Optimization,” Bioorganic and Medicinal Chemistry, Vol. 13, No. 4, 2005, pp. 1275-1283. doi:10.1016/j.bmc.2004.11.016
[10] P. Melnyk, V. Leroux, C. Sergheraert and P. Grellier, “Design, Synthesis and in Vitro Antimalarial Activity of an Acylhydrazone Library,” Bioorganic and Medicinal Chemistry Letters, Vol. 16, No. 1, 2006, pp. 31-35. doi:10.1016/j.bmcl.2005.09.058
[11] S. G. Kü?ükgüzel, S. Rollas, I. Kü?ükgüzel and M. Kiraz, “Synthesis and Antimycobacterial Activity of Some Coupling Products from 4-Aminobenzoic Acid Hydrazones,” European Journal of Medicinal Chemistry, Vol. 34, No. 12, 1999, pp. 1093-1100. doi:10.1016/S0223-5234(99)00129-4
[12] J. Patole, U. Sandbhor, S. Padhye, D. N. Deobagkar, C. Anson and A. E. Powell, “Structural Chemistry and in Vitro Antitubercular Activity of Acetylpyridine Benzoyl Hydrazone and Its Copper Complex against Mycobacterium smegmatis,” Bioorganic and Medicinal Chemistry Letters, Vol. 13, No. 1, 2003, pp. 51-55. doi:10.1016/S0960-894X(02)00855-7
[13] R. Maccari, R. Ottana and M. G. Vigorita, “In Vitro Advanced Antimycobacterial Screening of Isoniazid-Related Hydrazones, Hydrazides and Cyanoboranes: Part 14,” Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 10, 2005, pp. 2509-2513. doi:10.1016/j.bmcl.2005.03.065
[14] M. T. Cocco, C. Congiu, V. Onnis, M. C. Pusceddu, M. L. Schivo, A. Logu, E. Gürsoy and N. U. Güzeldemirci, “Synthesis and Primary Cytotoxicity Evaluation of New Imidazo[2,1-b]Thiazole Derivatives,” European Journal of Medicinal Chemistry, Vol. 42, No. 3, 2007, pp. 320-326. doi:10.1016/j.ejmech.2006.10.012
[15] N. Karal, A. Kocabalkanl, A. Gürsoy and O. Ate?, “Synthesis and Antitubercular Activity of 4-(3-Coumarinyl)3-Cyclohexyl-4-Thiazolin-2-One Benzylidenehydrazon,” II Farmaco, Vol. 57, No. 7, 2002, pp. 589-593. doi:10.1016/S0014-827X(02)01254-5
[16] V. Suni, M. R. Kurup and M. Nethaji, “Unusual Isolation of a Hemiaminal Product from 4-Cyclohexyl-3-Thiosemicarbazide and Di-2-Pyridyl Ketone: Structural and Spectral Investigations,” Journal of Molecular Structure, Vol. 749, No. 1-3, 2005, pp. 177-182. doi:10.1016/j.ejmech.2006.10.012
[17] G. Kuecuekguezel, A. Kocatepe, E. D. Clercq, F. ?ahin and M. Guelluece, “Synthesis and Biological Activity of 4-Thiazolidinones, Thiosemicarbazides Derived from Diflunisal Hydrazide,” Cheminform, Vol. 37, No. 34, 2006, pp. 353-359. doi:10.1002/chin.200634124
[18] A. P. Hoener, H. B. Frutos and J. C. Gauvin, “Novel OnePot Microwave Assisted Gewald Synthesis of 2-Acylamino Thiophenes on Solid Support,” Synlett, Vol. 1, No. 1, 2003, pp. 63-67. doi:10.1055/s-2003-36229

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