The synthesis and the study of the antitumor activity of 1,4-diaryl-5,6,7,8-tetrahydro-2,2a,8a triazacyclopenta[cd]azulene derivatives


  • S. A. Demchenko Institute of Pharmacology and Toxicology of National Academy of Medical Sciences Ukraine, Ukraine
  • Yu. A. Fedchenkova Nizhyn Mykola Gogol State University, Ukraine
  • L. S. Bobkova Institute of Pharmacology and Toxicology of National Academy of Medical Sciences Ukraine, Ukraine
  • L. P. Artemchuk Institute of Pharmacology and Toxicology of National Academy of Medical Sciences Ukraine, Ukraine
  • A. M. Demchenko Institute of Pharmacology and Toxicology of National Academy of Medical Sciences Ukraine, Ukraine



1, 4-diaryl-5, 6, 7, 8-tetrahydro-2, 2a, 8a-triazacyclopenta[cd]azulenes, antitumor activity


Aim. To synthesize, prove the structural framework and study the antitumor activity of 1,4-diaryl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta [cd]azulene derivatives.

Results and discussion. To determine the antineoplastic activity of 1-phenyl-4-aryl-5,6,7,8-tetrahydro-2,2a,8a-triazacyclopenta[cd]azulenes 7a-g and 1-(41-bromophenyl)-4-aryl-5,6,7,8-tetra-hydro-2,2a,8a-triazacyclopenta [cd]azulenes 7h-k the study in vitro was carried out on 60 lines of cancer cells (leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, prostate cancer and breast cancer) under the effect of the substance in the concentration of 10-5 mol/l according to the standard procedure of the mitotic activity assessment of the new potential bioactive compounds by the fluorescent coloring method (sulphorhodamine B as a dye) performed in the US National Institute of cancer within the Development Therapeutic Program.

Experimental part. 2-Methoxy-3,4,5,6-tetrahydro-7H-azepine was obtained by alkylation of caprolactam with dimethyl sulfate. 3-Phenyl or (41-bromophenyl)-(6,7,8,9-tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepine 4 a,b was obtained by condensation of 2-methoxy-3,4,5,6-tetrahydro-7H-azepine 1 with 4-bromobenzoic acid hydrazide and subsequent cyclization of the intermediate product. The 1Н-NMR spectra were recorded on a Bruker VXR-300 spectrometer (Germany) with the working frequency of 299.945 MHz, in DMSO-d6 using tetramethylsilane (TMS) as an internal standard. The purity of the compounds synthesized was controlled by TLC on the Silufol UV-254 plates in the system of chloroform – methanol (9 : 1).

Conclusions. New chemical compounds – derivatives of 1-phenyl(41-bromphenyl)-4-aryl-5,6,7,8-tetrahydro-2,2a,8a-triaza-cyclopenta[cd]azulene have been synthesized. The anticancer activity of the compounds obtained on 60 lines of tumor cells in the US National Cancer Institute has been studied. The high-active compounds that exhibit high levels of the antitumor activity have been identified.


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  1. Teregulova, D. R., Bakirov, B. A., & Akhmadeeva, L. R. (2018). Influence of polychemotherapy on cognitive functions in patients with lymphoproliferative diseases : literature review and personal clinical observations. Perm Medical Journal, 35 (6), 73–81.
  2. Gorbunova, T. V., Abdulrahman Ali, A.–A. G., Glekov, I. V., Susuleva, N. A., Shishkov, R. V., Ivanova, N. V., & Polyakov, V. G. (2018). Analysis of Treatment of the Outcomes in Pediatric Patients With Nasopharyngeal Cancer: A Retrospective Cohort Study. Oncopediatrics, 5 (4), 257–267.
  3. Protipuhlinnі zasobi. DMUPharm. Non scholae, sed vitae discimus. Available at:
  4. Kravchenko, T. V., Panasenko, O. І., Knish, Ye. G. (2016). Farmacevtichnij zhurnal, 5, 25–30.
  5. Mouridsen, H. Giobbie–Hurder, A., Goldhirsch A., Thürlimann B., Paridaens R, Smith I, Coates, A. S. (2009). Letrozole therapy alone or in sequence with tamoxifen in women with breast cancer. The New England Journal of Medicine, 361 (8), 766–776.
  6. Slomovitz, B. M., Taub, M. C., Huang, M., Levenback, C., & Coleman, R. L. (2019). A randomized phase II study of letrozole vs. observation in patients with newly diagnosed uterine leiomyosarcoma (uLMS). Gynecologic Oncology Reports, 27, 1–4.
  7. The ATAC (Arimidex, Tamoxifen Alone or in Combination) Trialists’ Group (2003). Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early–stage breast cancer. Cancer, 98(9), 1802–1810.
  8. Povoroznyuk, V. V., Bystrytska, M. A., & Musiienko, A. S. (2018). Osteoporosis in oncology. PAIN. JOINTS. SPINE, 8 (2), 101–110.
  9. “World Cancer Report”. (2008). International Agency for Research on Cancer. Retrieved 2011–02–26. (cancer statistics often exclude non-melanoma skin cancers such as basal cell carcinoma, which are common but rarely fatal). URL:
  10. Beverly A. Teicher, Paul A. Andrews. (Eds). (2004). Anticancer drug development guide: preclinical screening, clinical. Medical, 1, 450.
  11. Alley M.C, Scudiero, D. A., Monks, P. A., Hursey, M. L., Czerwinski, M. J., Fine, D. L., Abbott, B. J., Mayo, J. G., Shoemaker, R. H., Boyd, M. R. (1988). Feasibility of drug screening with panels of human tumor cell lines using a microculture Tetrazolium assay. Cancer Res, 48, 589–601.
  12. Carter, P. H., Scherle, P. A., Muckelbauer, J. A., Voss, M. E., Liu, R.-Q., Thompson, L. A., … Decicco, C. P. (2001). Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF. Proceedings of the National Academy of Sciences, 98 (21), 11879–11884.
  13. Grever, M. R., Schepartz, S. A., Chabner, B. A. (1992). The National Cancer Institute : cancer drug discovery and development program. Seminars in Oncol, 19 (6), 622–638.
  14. Granik, V. G., Zhidkova, A. M., Kuryatov, N. (1973). HGS, 11, 1532–1535.
  15. Petersen, S., & Tietze, E. (1957). Reaktionen Cyclischer Lactimäther mit Acylierten Hydrazinderivaten. Chemische Berichte, 90 (6), 909–921.




How to Cite

Demchenko, S. A.; Fedchenkova, Y. A.; Bobkova, L. S.; Artemchuk, L. P.; Demchenko, A. M. The Synthesis and the Study of the Antitumor Activity of 1,4-Diaryl-5,6,7,8-Tetrahydro-2,2a,8a triazacyclopenta[cd]azulene Derivatives. J. Org. Pharm. Chem. 2019, 17, 3-12.



Original Researches