Anticonvulsant Activity of a Combined Pharmacophore of Pyrazolo-pyridines with Lesser Toxicity in Mice

Abstract

Various 2-amino-6-[3-(substituted phenyl)-5-phenyl-4,5-dihydropyrazol-1-yl]-4-(substituted phenyl)nicotinonitriles (3a-t) were designed and synthesized by clubbing two active anticonvulsant pharmacophores pyrazole and pyridine. All the synthesized compounds possessed the pharmacophoric elements essential for good anticonvulsant activity. The anticonvulsant screening was performed by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. Two compounds 3i and 3s showed significant anticonvulsant activity in both the screens with ED50 values 17.5 mg/kg and 22.6 mg/kg respectively in MES screen and 154.1 mg/kg and 242.6 mg/kg respectively in scPTZ screen. They were also found to have no acute toxic effects in mice when tested at elevated doses.

Synthesis of 2-Amino-6-(2,3-dioxo-1,2,3,4-tetrahydroquinoxalin-1-yl)-4-(substituted)- phenylpyridine-3-carbonitrile Derivatives and their Antibacterial and Antifungal Activity

“…Nacetylation of compound (1) to yield N-acetyl-(1H,4H)quinoxaline-2,3-dione (2) was achieved by stirring compound (1) with acetylchloride in carbon tetrachloride for 3 hours. Now, compound (2) was refluxed with appropriate substituted benzaldehyde, malononitrile and ammonium acetate to undergo cyclization to yield 2-amino-6-(2,3-dioxo-1,2,3,4tetrahydroquinoxalin-1-yl)-4-(substituted)phenylpyridine-3-carbonitrile (3a-o) via Hantzsch Pyridine Synthesis 26 . Structures of all the newly synthesized compounds were confirmed on the basis of their spectral data interpretation.…”

A Review: Synthesis and Medicinal Importance of Nicotinonitriles and Their Analogous

“…These condensed with hydrazine hydrate in acetic acid to afford 74a – d . In the final step, the free acetyl group was condensed with the appropriate aldehydes 75 , malononitrile in ethanol in the presence of ammonium acetate to give the nicotinonitrile 76a – d (Scheme ) . All the synthesized compounds possessed good anticonvulsant activity.…”

“…Siddiqui et al . carried out the reaction of 4‐substituted acetophenones 72 with benzaldehyde in basic condition, lead to the formation of the corresponding chalcones 73a – d . These condensed with hydrazine hydrate in acetic acid to afford 74a – d .…”

“…All the synthesized compounds possessed good anticonvulsant activity. Nicotinonitrile 76i and 76s showed significant anticonvulsant activity with ED 50 values 17.5 and 22.6 mg/kg, respectively, in MES screen and 154.1 and 242.6 mg/kg, respectively, in scPTZ screen .…”

Design and synthesis of new series of 3‐cyanopyridine and pyrazolopyridine derivatives

“…Pyridine is one of the most popular moieties incorporated into the structure of wide range of biologically active compounds. Among these, cyanopyridines (nicotinonitriles) have various biological activities, as antimicrobial [8][9][10], anticancer [10][11], antihypertensive [12], analgesic, antipyretic, anti-inflammatory [13][14][15], antioxidant [16][17][18][19], anti-Alzheimer [20], and anticonvulsant [21]. On the other hand, some nicotinonitrile derivatives are used as electrical materials [22] and optical materials [23].…”