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Medicinal Chemistry Research

, Volume 26, Issue 12, pp 3158–3172 | Cite as

Design and synthesis of novel 2-(5-(4-aryl)-4,5-dihydro-1H-pyrazol-3-yl)-1-(substituted aminomethyl)-1H-benzimidazole as potent anticonvulsants

  • Pullagura Mallikarjuna Krishna Prasad
  • Raja Sundararajan
Original Research
  • 105 Downloads

Abstract

A variety of novel 2-(5-(4-aryl)-4,5-dihydro-1H-pyrazol-3-yl)-1-(substitutedaminomethyl)-1H-benzimidazole 5a5l have been synthesized from o-phenylenediamine by a multi-step synthesis. Antiepileptic screening of the title compounds was performed using maximal electroshock and subcutaneous pentylenetetrazole seizures tests while the neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 5d, 5e, 5f and 5l were found active in maximal electroshock model; while 5d, 5e, 5f and 5k showed significant antiepileptic activity in subcutaneous pentylenetetrazole seizure model. Further all these five compounds were administered to rats at 30 mg/kg dose in oral route and found that compounds 5e and 5f showed better activity than Phenytoin. These compounds 5e and 5f revealed protection in maximal electroshock after intraperitoneal administration at a dose of 30 mg/kg (0.5 h and 4.0 h). These compounds also provided protection in the subcutaneous pentylenetetrazole seizure at a dose of 100 mg/kg (0.5 h) and 300 mg/kg (4 h).

Keywords

Benzimidazole Pyrazole Epilepsy In vivo studies Neurotoxicity 

Notes

Acknowledgements

The authors gratefully acknowledge the Pfizer limited and GITAM University for providing infrastructure facilities to carry out this research work.

Compliance with ethical standards

Conflict of interests

The authors declares that they have no competing interests.

Supplementary material

44_2017_2010_MOESM1_ESM.pdf (4.7 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Pullagura Mallikarjuna Krishna Prasad
    • 1
  • Raja Sundararajan
    • 2
  1. 1.Pfizer LimitedPfizer CenterMumbaiIndia
  2. 2.Department of Pharmaceutical Chemistry, GITAM Institute of PharmacyGITAM UniversityVisakhapatnamIndia

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