Purposeful search of hypoglycemic agents among N-arylcarbamides and N-arylsulfamides of [2-(3-R-1Н-[1,2,4]triazole-5-yl)phenyl]amines

Authors

  • S. V. Kholodnyak
  • K. P. Shabelnik
  • S. I. Kovalenko
  • G. O. Gernova
  • S. D. Trzhеtsinskiy

DOI:

https://doi.org/10.14739/2409-2932.2015.2.45122

Keywords:

2-(3-R-1Н-[1, 2, 4]triazole-5-yl)phenyl]amines, 1, 4-triasole, Arylamine Acetylases Arylsulfates, N-arylcarbamides, N-arylsulfamides, Hypoglycemics

Abstract

Aim. Formation of N-arylcarbamides and N-arylsulfamides as result of interaction of 2-(3-R-1Н-[1,2,4]triazole-5-yl)phenyl]amines with electrophilic reagents (arylisocyanates and arylsulfonylchlorides) is described in presented article. The optimal conditions for mentioned reactions have been proposed.

Methods and results. It has been evaluated that N-arylcarbamides of 2-(3-aryl-1H-1,2,4-triazole-5-yl)phenyl]amines while heating over 90°C in glacial acetic acid undergo cyclisation followed by formation of corresponding 2-aryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6Н)-ones. Purity and structure of synthesized compounds has been proved by elemental analysis, 1H NMR-, chromato-mass and mass-spectra.

Conclusion. It has been established, that compound 2.1 during evaluation of specific pharmacologic activities on oral glucose tolerance test (OGTT), rapid insulin and adrenaline test models exhibited action which is comparable to activities of reference-drugs «Metformin» and «Gliclazide».

References

Starkova, N. Т. (2002) Кlinichna e`ndokrinologiya. Rukovodstvo [Clinical Endocrinology. leadership]. Saint Petersburg: Piter. [in Russian].

Mikhailov, V. V. (2001) Osnovy patologicheskoj fiziologii: Rukovodstvo dlya vrachej [Fundamentals of Pathophysiology: A Guide for Physicians]. Moscow: Medicina. [in Russian].

Navarrete-Vázquez, G., Morales-Vilchis, M. G., Estrada-Soto, S. Ramírez-Espinosa, J. J., Hidalgo-Figueroa, S., Nava-Zuazo, C., et al. (2014) Synthesis of 2-{2-[(α/β-naphthalen-1-ylsulfonyl)amino]-1,3-thiazol-4-yl}acetamides with 11β-hydroxysteroid dehydrogenase inhibition and in combo antisdiabetic activities. European Journal of Medicinal Chemistry, 74(3), 179–186. doi: 10.1016/j.ejmech.2013.12.042.

Kun, S., Bokor, É., Varga, G., Szőcs, B., Páhi, A., Czifrák, K., et al. (2014) New synthesis of 3-(β-D-glucopyranosyl)-5-substituted-1,2,4-triazoles, nanomolar inhibitors of glycogen phosphorylase. European Journal of Medicinal Chemistry, 76, 567–579. doi: 10.1016/j.ejmech.2014.02.041.

Raza, S., Srivastava S. P., Srivastava, D. S., Srivastava, A. K., Haq, W., & Katti, S. B. (2013) Thiazolidin-4-one and thiazinan-4-one derivatives analogous to rosiglitazone as potential antihyperglycemic and antidyslipidemic agents. European Journal of Medicinal Chemistry, 63, 611–620. doi: 10.1016/j.ejmech.2013.01.054.

Lipson, V. V., Shirobokova, M. G., & Petrova, O. N. (2013). 11β-gidroksisteroiddegidrogenaza 1 tipa – mi6en' dlja razrabotki peroral'nyh antidiabeti4eskih sredstv (obzor) [11β-Hydroxysteroid Dehydrogenase 1: Target for Oral Antidiabetic Drugs Design]. Khimiko-farmacevticheskij zhurnal, 47(2), 12–18. [in Russian].

Navarrete-Vázquez, G., Alaniz-Palacios, A., Hidalgo-Figueroa, S., González-Acevedo, C., Ávila-Villarreal, G., Estrada-Soto, S., et al. (2013) Discovery, synthesis and in combo studies of a tetrazole analogue of clofibric acid as a potent hypoglycemic agent. Bioorganic & Medicinal Chemistry Letters, 23(11), 3244–3247. doi: 10.1016/j.bmcl.2013.03.122.

Patil, V. S., Nandre, K. P., Ghosh, S., Rao, V. J., A Chopade, B., & Sridhar, B. (2013) Synthesis, crystal structure and antidiabetic activity of substituted (E)-3-(benzo[d]thiazol-2-ylamino)phenylprop-2-en-1-one. European Journal of Medicinal Chemistry, 59, 304-309. doi:10.1016/j.ejmech.2012.11.020.

Murugan, R., Anbazhagan, S., Narayanan, S. S. (2009) Synthesis and in vivo аntidiabetic activity of novel dispiropyrrolidines through [3+2] cycloaddition reactions with thiazolidinedione and rhodanine derivatives. European Journal of Medicinal Chemistry, 44(8), 3272–3279.

Madhavan, G. R., Chakrabarti, R., Kumar, S. K. B., Misra, P., Mamidi, R. N., Balraju, V., et al. (2001) Novel phthalazinone and benzoxazinone containing thiazolidinediones as аntidiabetic and hypolipidemic agents. European Journal of Medicinal Chemistry, 36(7), 627–637. doi: 10.1016/S0223-5234(01)01257-0.

Shingalapur, R. V., Hosamani, K. M., Keri, R. S., & Hugar, M. H. (2010) Derivatives of benzimidazole pharmacophore: Synthesis, anticonvulsant, antidiabetic,and DNA cleavage studies. European Journal of Medicinal Chemistry, 45(5), 1753–1759. doi: 10.1016/j.ejmech.2010.01.007.

Park, H., Hwang, K. Y., Kim, Y. H., Oh, K. H. Lee, J. Y., & Kim, K. (2008) Discovery and biological evaluation of novel α-glucosidase inhibitors with in vivo antidiabetic effect. Bioorganic & Medicinal Chemistry Letters, 18(13), 3711–3715. doi: 10.1016/j.bmcl.2008.05.056.

Kovalenko, S. I., Antypenko, L. M., Bilyi, A. K., Kholodnyak, S. V., Karpenko, O. V., Antypenko, O. M., et al. (2013). Synthesis and anticancer activity of 2-аlkyl(alkaryl-, aryl-, heteryl-)-[1,2,4]triazolo[1,5-c]quinazolines. Scientia Pharmaceutica, 81(2), 359–391. doi: 0.3797/scipharm.1211-08.

Kholodniak, S. V., Zhernova, H. О., Shabelnik, К. P., et al. (patentee) (2014) Patent Ukrainy №94667 МPК (2009) С07D 253/00. Zamishcheni [2-(3-R-1Н-[1,2,4]triazol-5-il)fenil]aminy, shcho proiavliaiut hipohlikemichnu aktyvnost. Biul., 22. [in Ukrainian].

Коvаlеnко, S. І., Voloshyna, V. О., & Каrpеnко, О. V. (2010) Syntez ta nukleofilne rozmishchennia 2-R-[1,2,4] triazolo[1,5-c]khinazoliniv [Synthesis and nucleophilic cleavage of 2-R- [1,2,4] triazolo [1,5-c] quinazolin]. Zhurnal orhanichnoi tа farmatsevtychnoi khimii, 8(2(30)), 48–56. [in Ukrainian].

(2003) Etuka likaria tа prava liudyny: polozhennia prо vykorystannia tvaryn u biomedychnykh doslidakh [Ethics doctor and human rights: the provisions on the use of animals in biomedical experiments]. Eksperymentalna ta klinichna fiziolohiia i biokhimiia, 2(22), 108–109. [in Ukrainian].

Vavilova, L. L., Kriachok, Т. А., & Talaieva, Т. V. (2009) Modeliuvannia insulinorezystentnosti tа kompleksu metabolichnykh porushen zа dopomoghoiu deksametazonu [Simulation of complex insulin resistance and metabolic disorders using dexamethasone]. Fiziolohichnyi zhurnal, 2(3), 75–80. [in Ukrainian].

Stefanov, О. V. (2001) Doklinichni doslidzhennia likarskykh zasobiv [Preclinical studies of drugs]. Кyiv. [in Ukrainian].

Rebrova, О. Yu. (2006) Statisticheskij analiz medicinskikh dannykh [Statistical analysis of medical data]. Moscow: Media Sfera. [in Russian].

Bilyi, A. K., Kovalenko, S. I., Kamyshnyi, O. M., et al. (2013) Efektyvni меtody syntezu 2-hetaryl-[1,2,4]triazolo[1,5-c]khinazolin-5(6N)-oniv ta yikh antybakterial'na aktyvnist'. [Effective methods of synthesis of 2-hetaryl- [1,2,4] triazoles [1,5-c] quinazolin-5 (6H) -ones and their antibacterial activity]. Zaporozhskij medicinskij zhurnal, 6(81), 83–87. [in Ukrainian].

Downloads

How to Cite

1.
Kholodnyak SV, Shabelnik KP, Kovalenko SI, Gernova GO, Trzhеtsinskiy SD. Purposeful search of hypoglycemic agents among N-arylcarbamides and N-arylsulfamides of [2-(3-R-1Н-[1,2,4]triazole-5-yl)phenyl]amines. Current issues in pharmacy and medicine: science and practice [Internet]. 2015Jul.14 [cited 2024Nov.24];(2). Available from: http://pharmed.zsmu.edu.ua/article/view/45122

Issue

No. 2 (2015)

Section

Synthesis of the biologically active compounds

License

Authors who publish with this journal agree to the following terms:

    1. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.     Лицензия Creative Commons
    2. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
    3. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access)