Drug Res (Stuttg) 2021; 71(04): 199-203
DOI: 10.1055/a-1291-7554
Original Article

Synthesis of Novel Triazolyl/Oxadiazolyl/Thiadiazolyl-Piperazine as Potential Anticonvulsant Agents

Archana Archana
1   Medicinal Chemistry Laboratory, Department of Chemistry, Meerut College, Meerut, Uttar Pradesh, India
› Author Affiliations

Abstract

Reaction of piperazine with chloroacetylchloride in dry acetone yield compound 1 , which on reaction with hydrazine hydrate yielded compound 2, which was further reacted with various substituted phenylisothiocyanates in absolute alcohol to afford compounds 3–8 i. e. 2-(carbazolylacetyl)-N-(substitutedphenyl)-hydrazinepiperazinothioamides. Compounds 3–8 on reaction with aqueous NaOH, ethanolic NaOH and conc. H2SO4 afford triazoles 9–14, oxadiazoles 15–20 and thiadiazoles 21–26 respectively. Twenty four newly synthesized compounds were evaluated for their anticonvulsant activity and acute toxicity. The structures of these compounds were established on the basis of analytical and spectral data.



Publication History

Received: 27 June 2020

Accepted: 12 October 2020

Article published online:
12 January 2021

© 2021. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Suryanshi HR, Rathore MM. Synthesis and biological activities of piperazine derivatives as antimicrobial and antifungal agents. Org Commun 2017; 10: 228-238
  • 2 Chandrika NT, Shrestha SK, Ngo HX. et al. Alkylated piperazines and piperazine-azole hybrids as antifungal agents. J Med Chem 2018; 61: 158-173
  • 3 Chaudhary PK, Verma AK, Singh D. et al. Synthesis and antimicrobial activity of N-alkyl and N-aryl piperazine derivatives. Bio Med Chem 2006; 14: 1818-1826
  • 4 Mallesha L, Mohana KN. Synthesis, antimicrobial and antioxidant activities of 1-(1,4-benzodioxane-2-carbonyl) piperazine derivatives. Eur J Chem 2011; 2: 193-199
  • 5 Choo HYP, Chung BJ, Chung SH. Synthesis of piperazine derivatives and evaluation of their antihistamine and antibradykinin effects. Bioorg Med Chem Lett 1999; 9: 2727-2730
  • 6 Howard HR, Lowe JA, Seeger TF. et al. 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem 1996; 39: 143-148
  • 7 Chen Y, XU X, Liu X. et al. Synthesis and evaluation of a series of 2-substituted-5-thiopropylpiperazine (piperidine)-1,3,4- oxadiazoles derivatives as atypical antipsychotics 2012; 7: 1-10
  • 8 Mukherjee D, Mukhopadhyay A, Bhat KS. et al. characterization and anticonvulsant activity of substituted 4-chloro-2-(piperazin-1-yl )quinazolines. Int J Pharm Pharm Sci 2014; 6: 567-571
  • 9 Kaminski K, Wiklik B, Obniska J. Synthesis and anticonvulsant activity of new N-phenyl-2-(4-phenylpiperazin-1-yl) acetaminde derivatives. Med Chem Res 2015; 24: 3047-3061
  • 10 Kaminski K, Rzepka S, Obniska J. Synthesis and anticonvulsant activity of new 1-[2-oxo-2(4-phenylpiperazin-1-yl) ethyl] pyrrolidine-2,5-diones. Bioorg Med Chem Lett 2011; 21: 5800-5803
  • 11 Plech T, Kapron B, Luszczki JJ. et al. Studies on the anticonvulsant activity and influence on GABA-ergic neuro-transmission of 1,2,4-triazole-3-thionebased compounds. Molecules 2014; 19: 11279-11299
  • 12 Plech T, Luszczki JJ, Wujec M. et al. Synthesis, characterization and preliminary anticonvulsant evaluation of some 4-alkyl-1,2,4-triazoles. Eur J Med Chem 2013; 60: 208-215
  • 13 Deng XQ, Song MX, Zheng Y. et al. Design, synthesis and evaluation of the antidepressant and anticonvulsant activities of triazole-containing quinolinones. Eur J Med Chem 2014; 73: 217-224
  • 14 Kapron B, Czarnomysy R, Wysokiniski M. et al. 1,2,4-Triazole-based anticonvulsant agents with additional ROS scavenging activity are effective in a model of pharmacoresistant epilepsy. J Enzyme Inhibition and Med Chem 2020; 35: 993-1002
  • 15 Almmasirad A, Tabatabai SA, Faizi M. et al. Synthesis and anticonvulsant activity of new 2-substituted -5-[2-(2-fluorophenoxyphenyl)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg Med Chem 2004; 14: 6057-6059
  • 16 Zarghi A, Tabatabai SA, Faizi M. et al. Synthesis and anticonvulsant of new 2-substituted-5(2-benzyloxyphenyl)-1,3,4-oxadiazoles. Bioorg Med Chem Lett 2005; 15: 3126-3129
  • 17 Zarghi A, Hamedi S, Tootooni F. et al. Synthesis and pharmacological evaluation of new 2-substituted-5-{2-[(2-halobenzyl)thiophenyl}-1,3,4-oxadiazoles as anticonvulsant agents. Sci Pharm 2008; 76: 185-201
  • 18 Almasirad A, Vousooghi N, Tabatabai SA. et al. Shafiee A. Synthesis, anticonvulsant and muscle reluctant activities of substituted 1,3,4-oxadiazole, 1,3,4-thiadiazole and 1,2,4-triazole. Acta Chimica Solvenica 2007; 54: 317-324
  • 19 Nazar S, Siddiqui N, Alam O. Recent progress of 1,3,4-oxadiazoles as anticonvulsants: Future horizons. Archiv der Pharmazie 2020; 353: 1-12
  • 20 Foroumadi A, Sheibani V, Sakhteman A. et al. Synthesis and anticonvulsant activity of novel 2-amino-5-[4-chloro-2-(2-chlorophenoxy)phenyl]-1,3,4-thiadiazole derivatives. Daru 2007; 15: 89-93
  • 21 Sarafroz M, Khatoon Y, Ahmad N. et al. Synthesis, characterization and anticonvulsant activity of novel fused 1,2,4-triazolo-1,3,4-thiadiazoles. Oriental J Chem 2019; 35: 64-70
  • 22 Toolabi M, Khoramjouy M, Aghcheli A. et al. Synthesis and radioligand-binding assay of 2,5-disubstituted thiadiazoles and evaluation of their anticonvulsant activities. Arch Pharm 2020; e2000066: 1-9
  • 23 Toman JEP, Swinyard EA, Goodman LS. Properties of maximal seizures and their alteration by their anticonvulsant drugs and other agents. J Neurophysiol 1946; 9: 231-240
  • 24 Smith QE. In: Pharmacological screening tests progress in medicinal chemistry-1, Butterwort’s London. Medicinal Chem 1960; 1: 1-33