Synthesis, characterization and pharmacological evaluation of some new 6(2-Chloro 3,5-substituted phenyl)-1,2,4-triazine derivatives
DOI:
https://doi.org/10.7439/ijpc.v5i5.2014Abstract
6(2-Chloro 3,5-substituted phenyl)-1,2,4-triazine derivatives were synthesized and studied for evaluation of anticonvulsant activity by maximal electroshock test and neurotoxicity by rotarod motor test. Some compounds were displayed protection against induced seizures at a dose level 100 mg/kg after 0.5 and 4.0 h and while some compounds were displayed neurotoxicity at highest administered dose (300 mg/kg) after 4.0 h. Screening data revealed that one compound was found most active in series with little CNS depressant effect without neurotoxicity when compared to standard drugs Phenytoin and Carbamazepine.Downloads
References
Prasad AN, Prasad C. In Pediatric Epilepsy: Diagnosis and Therapy; Demos Publishers, New York 2001.
Verma M, Pandeya SN, Singh KN, Stables JP. Anticonvulsant activity of schiff bases of Isatin derivatives. Acta Pharm 2004; 54: 49-56.
Secretariats of WHO/IBE/ILAE, Global campaign against epilepsy, atlas: epilepsy care in the world, programme for neurological diseases and neuroscience, Department of Mental Health and Substance Abuse, World Health Organization, Geneva, 2009.
Dimmock JR, Pandeya SN, Quail JW, Pugazhenthi U, Allen TM, Kao GY. Evaluation of the semicarbazones, thiosemicarbazones and biscarbohydrazones of some aryl alicyclic ketones for anticonvulsant and other biological properties. Eur J Med Chem 1995; 30: 303-14.
Duncan JS. The promise of new antiepileptic drugs. Br J Clin Pharmacol 2002; 53:123-31.
Ma X, Poon TY, Wong PTH, Chui WK. Synthesis and in vitro evaluation of 2,4-diamino-1,3,5-triazine derivatives as neuronal voltage-gated sodium channel blockers. Bioorg Med Chem Lett 2009; 19(19): 5644-5647.
Yogeeswari P, Sriram D, Thirumurugan R, Raghavendran RV, Sudhan K, Pavana RK, et al. Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants:hybrid pharmacophore-based design. J Med Chem 2005; 48: 6202-11.
Unverferth K, Engel J, Hofgen N, Rostock A, Gunther R, Lankau HJ, et al. Synthesis, anticonvulsant activity, and structure-activity relationships of sodium channel blocking 3-aminopyrroles. J Med Chem 1998; 41(1): 63-73.
Hlavac J, Buchtik R, Slouka, J, Hradil P, Wiedermannova I. Synthesis of oxo analogs of Lamotrigine and related compounds. Arkivoc 2003; 1: 22-28.
Aanandhi VM., George S, Vaidhyalingam V. Synthesis and antimicrobial activities of 1-(5-substituted-2-oxo indolin-3-ylidene)-4-(substituted pyridin-2-yl)thiosemicarbazide. Arkivoc 2008; 11: 187-94.
Eid MM, Kadry AM, Hassan RA. Synthesis and reactions of some 6-(2-hydroxy-1-naphthyl)-1,2,4-triazines. J Heterocycl Chem 1988; 25(4): 1117-18.
Krall RL, Penry JK, White BG, Kupferbeng HJ, Swinyard EA. Antiepileptic drug development: II. Anticonvulsant drug screening. Epilepsia 1978; 19: 409-28.
Porter RJ, Cereghino JJ, Gladding GD, Hessie BJ, Kupferberg HJ, Scoville B. Antiepileptic drug development program. Cleveland Clin Q 1984; 51: 293-305.
Dunham MS, Miya TA. A note on a simple apparatus for detecting neurological deficit in rats and mice. J Amer Pharm Assoc Sci 1957; 46: 208.
Porsolt RD, Anton G, Blanet N, Jalfer M. Behavioral despair in rats: A new model sensitive to antidepressant treatments. Eur J Pharmaco 1978; 47: 379-86.
Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 2000; 43: 3714-17.
Lipinskipinski CA, Lombardo L, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 2001; 46: 03-26.
Molinspiration Cheminformatics, Bratislava, Slovak Republic, http://www.molinspiration.com/services/properties.html. Accessed 16 February 2014.
Zhao YH, Abraham MH, Lee J, Hersey A, Luscombe NC, Beck G, et al. Rate-limited steps of human oral absorption and QSAR studies. Pharm Res 2002;19:1446-57.
http://www.organic-chemistry.org. Accessed 10 February 2014.
Tekto IV. Computing chemistry on the web. Drug Discovery Today 2005; 10(22): 1497-1500.
Dimmock JR, Vashishtha SC, Stables JP. Anticonvulsant properties of various acetylhydrazones,oxamoylhydrazones and semicarbazones derived from aromatic and unsaturated carbonyl compounds. Eur J Med Chem 2000a; 35: 241-48.
Dimmock JR, Vashishtha SC, Stables JP. Ureylene anticonvulsants and related compounds. Pharmazie 2000b; 55; 490-494.
White HS, Woodhead JH, Franklin MR, Mattson RH, Meldrum BS. Antiepileptic drugs, Rave Press, New York 1995.
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