Safety assessment of the 4- (6-phenyl-7h - [1,2,4] triazolo [3,4-b] [1,3,4] thiadiazine-3- yl) -aniline compound and the effects of the substance on respiration and cardiac activity
DOI:
https://doi.org/10.37547/ajbspi/Volume05Issue03-05Keywords:
Acute toxicity, accumulation, number of breathsAbstract
4-(6-phenyl-7H-[1,2,4]-triazolo-[3,4-b] - [1,3,4] - thiadiazine-3- yl) - aniline compound belongs to the group of triazole derivatives, belongs to class IV low-toxic compounds in acute toxicity, and sodium belongs to the compounds of this group, taking into account the presence of Due to its ability to block ion channels, it can be concluded that the 1.0 mg/kg dose studied during the experiment led to bradycardia in exchange for a decrease in the activity of the sinus node, which is considered the main regulator of the first-order heart rhythm.
References
Strine TW, Kobau R, Chapman DP, Thurman DJ, Price P, Balluz LS. Psychological distress comorbidities and health behaviors among U.S. adults with seizures: results from the 2002 National Health Interview Survey. Epilepsia. 2005 Jul;46(7):1133-9. doi:10.1111/j.1528-1167.2005.01605.x, PMID 16026567.
Ashhar MU, Ahmad MZ, Jain V, Agarwal NB, Ahmad FJ, Jain GK. Intranasal pitavastatin attenuates seizures in different experimental models of epilepsy in mice. Epilepsy Behav. 2017
Oct 1;75:56-9. doi: 10.1016/j.yebeh.2017.07.004, PMID 28826009.
Soares DA Silva P, Pires N, Bonifacio MJ, Loureiro AI, Palma N, Wright LC. Eslicarbazepine acetate for the treatment of focal epilepsy: an update on its proposed mechanisms of action. Pharmacol Res Perspect. 2015 Mar;3(2):e00124. Doi:10.1002/prp2.124, PMID 26038700
Hanada T. The discovery and development of perampanel for the treatment of epilepsy. Expert Opin Drug Discov. 2014 Apr 1;9(4):449-58. doi: 10.1517/17460441.2014.891580, PMID 24559052.
Large CH, Sokal DM, Nehlig A, Gunthorpe MJ, Sankar R, Crean CS. The spectrum of anticonvulsant efficacy of retigabine (ezogabine) in animal models: implications for clinical use.
Epilepsia. 2012 Mar;53(3):425-36. doi: 10.1111/j.1528- 1167.2011.03364.x, PMID 22221318.
Kamboj VK, Verma PK, Dhanda A, Ranjan S. 1,2,4-triazole derivatives as a potential scaffold for anticonvulsant activity. Cent Nerv Syst Agents Med Chem. 2015 Apr 1;15(1):17-22. doi:
2174/1871524915666150209100533, PMID 25675400.
Ben Menachem E. Medical management of refractory epilepsy practical treatment with novel antiepileptic drugs. Epilepsia. 2014 Jan;55 Suppl 1:3-8. doi: 10.1111/epi.12494, PMID 24400690.
Luszczki JJ, Plech T, Wujec M. Effect of 4-(4-bromophenyl)-5-(3- chlorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione on the anticonvulsant action of different classical antiepileptic drugs in the mouse maximal electroshock induced seizure model. Eur J Pharmacol. 2012 Sep 5;690(1-3):99-106. doi: 10.1016/j.ejphar.2012.06.023, PMID 22732650.
Loring DW, Meador KJ. Cognitive side effects of antiepileptic drugs in children. Neurology. 2004 Mar 23;62(6):872-7. doi: 10.1212/01.wnl.0000115653.82763.07, PMID 15037684.
Chen B, Choi H, Hirsch LJ, Katz A, Legge A, Buchsbaum R. Psychiatric and behavioral side effects of antiepileptic drugs in adults with epilepsy. Epilepsy Behav. 2017 Nov 1;76:24-31. doi:
1016/j.yebeh.2017.08.039, PMID 28931473.
Deka D, Chakravarty PI, Purkayastha AY. Evaluation of the anticonvulsant effect of aqueous extract of Centella asiatica in albino mice. Int J Pharm Pharm Sci. 2017;9(2):312-4. doi:
22159/ijpps.2017v9i2.15483.
Karakucuk Iyidogan A, Basaran E, Tatar Yilmaz G, Oruc Emre EE. Development of new chiral 1,2,4-triazole-3-thiones and 1,3,4-thiadiazoles with promising in vivo anticonvulsant activity targeting GABAergic system and voltage-gated sodium channels (VGSCs). Bioorg Chem. 2024 Oct 1;151:107662. doi:10.1016/j.bioorg.2024.107662, PMID 39079390.
Rani S, Teotia S, Nain S. Recent advancements and biological activities of triazole derivatives: a short review. Pharm Chem J. 2024 Apr 15;57(12):1909-17. doi: 10.1007/s11094-024-03096- z.
Mula M. GABAergic drugs in the treatment of epilepsy: modern or outmoded? Future Med Chem. 2011 Feb;3(2):177-82. doi: 10.4155/fmc.10.296, PMID 21428812.
Froestl W. An historical perspective on GABAergic drugs. Future Med Chem. 2011 Feb;3(2):163-75. doi: 10.4155/fmc.10.285, PMID 21428811.
Rahimboyev, S., Sanoev, Z., Hamroyev, T., Abdinazarov, I., Rashidov, S., Ismoilova, D.., & Elmuradov, B. (2025). 5-(p-aminofenil)-4-amino-1,2,4-triazol-3(2H)-tionning o‘tkir zaharliligi va tutqanoqqa qarshi faolligi. Евразийский журнал медицинских и естественных наук, 5(2 Part 2), 110–118. извлечено от https://in-academy.uz/index.php/EJMNS/article/view/46508
Sanoev Z.I., Ismailova D.S., Rakhimboev S.D., Tolibovich T.T., Elmuradov B.J., Abdinazarov I.T., Rashidov S.Z. (2023). Synthesis And Research Anticonvulsant Activity Of Annulated Triazolo-thiadiazine Derivative In Laboratory Animals. Biomedical & Pharmacology Journal. Vol. 16(4), p. 2457-2467.
Matin MM, Matin P, Rahman MR, Ben Hadda T, Almalki FA, Mahmud S. Triazoles and their derivatives: chemistry synthesis and therapeutic applications. Front Mol Biosci. 2022 Apr
;9:864286. doi: 10.3389/fmolb.2022.864286, PMID 35547394, PMCID PMC9081720.
Zhang Y, Wang M, Ahmed M, HE L, JI M, QI Z. Synthesis fungicidal activity and SAR of 3,4-dichloroisothiazole based cycloalkyl sulfonamides. Bioorg Med Chem Lett. 2019 Jun 1;29(11):1345-9. doi: 10.1016/j.bmcl.2019.03.047, PMID 30956010.
Zhang Y, Wang M, Ahmed M, He L, JI M, QI Z. Synthesis fungicidal activity and SAR of 3,4-dichloroisothiazolebased cycloalkylsulfonamides. Bioorg Med Chem Lett. 2019;29(11):1345-49. doi: 10.1016/j.bmcl.2019.03.047, PMID 30956010.
Sanoyev, Z. (2025). 1-(4´-metoksifenil)-6,7dimetoksi-1,2,3,4-tetragidroizoxinolinning tutqanoqqa qarshi faolligi. Евразийский журнал медицинских и естественных наук, 5(1), 285–293. извлечено от https://in-academy.uz/index.php/EJMNS/article/view/44142.
Sanoev, Z. I., & Mirzaev, Y. R. (2020). Pharmacological activity of the possessing new atypical neuroleptics 1-phenyltetrahydroisoquinoline structure. The American Journal of Medical Sciences and Pharmaceutical Research, 18-26.
Sanoev, Z. I., & Mirzaev, Y. R. (2021). Research of a New Atypical Neuroleptic 1-(3, 4-Methylenedioxyphenyl)-6, 7-Methylenedioxy-1, 2, 3, 4-Tetrahydroisoquinoline on the Central Nervous System. Annals of the Romanian Society for Cell Biology, 25(2), 2363-2369.
Turan Zitouni G, Sivaci M, Kilic FS, Erol K. Synthesis of some triazolyl-antipyrine derivatives and investigation of analgesic activity. Eur J Med Chem. 2001 Aug 1;36(7-8):685-9. doi:10.1016/s0223-5234(01)01252-1, PMID 11600237.
Bekircan O, Kuxuk M, Kahveci B, Kolayli S. Convenient synthesis of fused heterocyclic 1,3,5-triazines from some N-acyl imidates and heterocyclic amines as anticancer and antioxidant agents. Arch Pharm Int. 2005 Aug;338(8):365-72. doi: 10.1002/ardp.200400964, PMID 16041836.
Wade PC, Vogt BR, Kissick TP, Simpkins LM, Palmer DM, Millonig RC. 1-Acyltriazoles as antiinflammatory agents. J Med Chem. 1982 Mar;25(3):331-3. doi: 10.1021/jm00345a021, PMID 6461764.
Mahdavi M, Akbarzadeh T, Sheibani V, Abbasi M, Firoozpour L, Tabatabai SA. Synthesis of two novel 3-amino-5-[4-chloro-2- phenoxyphenyl]-4H-1,2,4-triazoles with anticonvulsant activity. Iran J Pharm Res. 2010;9(3):265-9. PMID 24363736.
Modzelewska Banachiewicz B, Kalabun J. Synthesis and biological action of 5-oxo-1,2,4-triazine derivatives. Pharmazie. 1999 Jul 1;54(7):503-5. PMID 10445245.
Gupta D, Jain DK. Synthesis antifungal and antibacterial activity of novel 1,2,4-triazole derivatives. J Adv Pharm Technol Res. 2015 Jul 1;6(3):141-6. doi: 10.4103/2231-4040.161515, PMID 26317080.
Gao F, Wang T, Xiao J, Huang G. Antibacterial activity study of 1,2,4-triazole derivatives. Eur J Med Chem. 2019 Jul 1;173:274- 81. doi: 10.1016/j.ejmech.2019.04.043, PMID 31009913.
Gulerman N, Rollas S, Kiraz M, Ekinci AC, Vidin A. Evaluation of antimycobacterial and anticonvulsant activities of new 1-(4-fluorobenzoyl)-4-substituted thiosemicarbazide and 5-(4-
fluorophenyl)-4-substituted-2,4-dihydro-3H-1,2,4-triazole-3-thione derivatives. Farmaco. 1997 Nov 1;52(11):691-5. PMID9550096.
Ikizler AA, Johansson CB, Bekircan O, Celik C. Drug synthesis. Acta Poloniae Pharnaceutica–Drug Research. 1999;56(4):283-8.
Shalini M, Yogeeswari P, Sriram D, Stables JP. Cyclization of the semicarbazone template of aryl semicarbazones: synthesis and anticonvulsant activity of 4,5-diphenyl-2H-1,2,4-triazol-3(4H) one. Biomed Pharmacother. 2009 Mar 1;63(3):187-93. doi:10.1016/j.biopha.2006.04.002, PMID 19422088.
Siddiqui N, Ahsan W. Triazole incorporated thiazoles as a new class of anticonvulsants: design, synthesis and in vivo screening. Eur J Med Chem. 2010 Apr 1;45(4):1536-43. doi: 10.1016/j.ejmech.2009.12.062, PMID 20116140.
Almasirad A, Tabatabai SA, Faizi M, Kebriaeezadeh A, Mehrabi N, Dalvandi A. Synthesis and anticonvulsant activity of new 2-substituted-5- [2-(2-fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg Med Chem Lett. 2004 Dec 20;14(24):6057-9. doi: 10.1016/j.bmcl.2004.09.072, PMID15546729.
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Copyright (c) 2025 Rahimboev Suhrob Davlatyor o‘g‘li, Sanoev Zafar Isomiddinovich, Khamroyev Tolmas Tolibovich, Abdinazarov Ibrokhimjon Tuychiyevich, Rashidov Sohib Zamon o‘g‘li, Ismoilova Dilnoza Safaraliyevna, Elmuradov Burkhon
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