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Synthesis, anticonvulsant and CNS depressant activity of some new bioactive 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea
Authors:Sushil K. Kashaw   Varsha Kashaw   Pradeep Mishra   N.K. Jain  J.P. Stables
Affiliation:aPharmaceutical Chemistry Division, Department of Pharmaceutical Sciences, Dr. H.S. Gour University, Sagar 470003, India;bPreclinical Pharmacology Section, Epilepsy Branch, National Institutes of Health, Bethesda, MD 20892-9020, USA
Abstract:Several new 1-(4-substituted-phenyl)-3-(4-oxo-2-phenyl/ethyl-4H-quinazolin-3-yl)-urea were synthesized and screened for anticonvulsant, CNS depressant and sedative-hypnotic activity in the mice. After i.p. injection to mice at doses of 30, 100, and 300 mg/kg body weight synthesized compounds were examined in the maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) induced seizure models in mice. Spectroscopic data and elemental analysis were consistent with the newly synthesized compounds. The neurotoxicity was assessed using the rotorod method. Compounds E1, E6, E9, E12, P3, P4 and P6 were found to be active in the MES screen whereas E1, P4, P6 and P11 were found to be active in the scPTZ screen. All except E6, E11 and P6 showed more than 50% decrease in locomotor activity at 1 h of compound administration via actophotometer screen. CNS depressant activity screened with the help of the forced swim method resulted into some potent compounds. All the compounds were found to exhibit potent CNS depressants activity as indicated by increased immobility time. It can be concluded that newly synthesized compounds possessed promising CNS activities.
Keywords:4(3H)-Quinazolinones   MES   Subcutaneous pentylenetetrazole induced seizure   CNS depressants activity
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