Indian Journal of Chemistry Vol. 47B, April 2008, pp. 626-629 Note Synthesis and pharmacological screening of some 1,4-dihydropyridine and their derivatives for anticonvulsant activity Shashikant R Pattan* 1 , S S Purohit 1 , V P Rasal 2 , S Mallya 3 , S C Marihal 3 , A B Khade & M S Paschapur 2 1 Dept of Medicinal Chemistry, K L E S’s College of Pharmacy, Belgaum 590 010, India. 2 Dept of Pharmacology, K L E S’s College of Pharmacy, Belgaum 590 010, India. 3 Dept of Pharmacology, Goa College of Pharmacy, Panjim, Goa, 403001, India. E-mail: shashipattan@yahoo.com Received 23 November 2006; accepted (revised) 25 January 2008 A new series of 1,4-dihydropyridine and their derivatives have been synthesized and the structures of the compounds have been confirmed by IR and NMR. The title compounds are evaluated for anticonvulsant activity by maximal electroshock method. Some of these compounds have been found to exhibit excellent anticonvulsant activity. Keywords: Anticonvulsant, antihypertensive, 1,4-dihydropyr- idine. 1,4-Dihydropyridine 1,2 are well known as calcium channel blockers and have emerged as one of the important classes of drugs for the treatment of hypertension 3 . Recently reported studies have shown that compounds possessing 1,4-dihydropyridine nucleus possess variety of biological activities including antimicrobial agents 4 , myocardial infarction 5 , neuroprotectant 6 . Epileptic seizures have been known to represent an occasional discharge in the nervous tissue 7 , characterized by recurrent paroxysmal changes in the neurological functions caused by abnormalities in the electrical activity of the brain, infact epileptiform burst are often associated with influx of calcium ions in to nerve cells and a decrease in the extracelluar concentration of calcium precedes the onset of seizures in the many experimental models 8 . Anticonvulsant therapy however is neither universally effective nor invariably safe. Moreover blockers of voltage dependant Ca 2+ channels display anticonvulsant activity in various models of experi- mental convulsions and in humans 9 . The above examples and instances demonstrate the potential use of novel 1,4-dihydropyridine derivatives as a source of valuable drug candidates for anticonvulsant activity 10 . In the present work nine new 1,4-dihydropyridine derivatives were synthesized and characterized (Table I) and evaluated for their anticonvulsant activity. Experimental Section All melting points were determined in open capillary method and are uncorrected. IR spectra were recorded on Thermo Nicolet IR 200 spectrophotometer using KBr disc method. Purity of the compounds was checked on silica Gel TLC plates. 1 H NMR spectra (DMSO-d 6 ) were recorded on BRUKER amx-400 MHz using TMS as internal standard (chemical shift in δ ppm). Combustion analysis data here found to be within the limits of permissible errors. General method for preparation of N-substi- tuted aryl acetoacetamide 3 11,12 . An equimolar amount of ethyl acetate 1 and different aryl amine 2 were taken in a round bottom flask and dissolved in alcohol and refluxed for about 2-3 hr. The reaction mixture was cooled. The solid that separated out was filtered, washed with cold water and dried. The crude solid of anilide 3 was purified by recrystallization twice from appropriate solvent to give colourless crystals. IR (KBr): 3449 (NH), 3270 (CH-CH), 1701 (CONH), 1672 (C=O),1457 (C-N), 836, 748 cm -1 (CH=CH). (Scheme I) General method for preparation of 1,4-dihydro- pyridine. N-aryl (substituted) acetoacetamide (0.01 mole) was dissolved in methanol and an appropriate aldehyde (0.05 mole) was added followed by the addition of excess of ammonia (25%). The reaction mixture was mechanically stirred for 10 min. and then heated on water bath under reflux for 10-12 hr. Methanol was removed under reduced pressure and cooled. The product thus separated was filtered and washed with methanol. It was purified by recrystallization from alcohol to give yellowish crystalline compound. IR (KBr): 3546 (OH), 3243 (CH-CH aromatic str.), 1646 (C=O), 559 (C=N), 832, 746 cm -1 (CH-CH def.) General method for preparation of 1,4-dihydro- 2,6-dimethyl- 4-{4-[3-(piperidine / morpholine / 2- aminopyrazine/1-amino-4-methylpiperazine)-2-hy- droxypropoxy]-phynyl}-pyridine-3,5-carbamoyl