Synthesis of and Pharmacological Studies on the Antidepressant and Anticonvulsant Activities of Some 1,3,5-Trisubstituted Pyrazolines

Abstract

Summary Eighteen 1-phenyl-, 1-thiocarbamoyl-and 1-N-substitutedthiocarbamoyl-3-phenyl-5-heteroaryl-2-pyrazoline derivatives were synthesized and tested for their antidepressant and anticonvulsant activities. Their chemical structures were proved by spectral and microanalysis. The antidepressant activities of the compounds were investigated by the ?forced swimming test?. Results showed that compounds II-a,b,c, III-1b,1c,4a showed activities equivalent to or higher than pargyline hydrochloride (CAS 306-07-0) and tranylcypromine sulfate (CAS 13492-01-8) that were used as reference antidepressant drugs. Anticonvulsant activities of the compounds were determined by maximal electroshock seizure (MES), subcutaneous metrazol (ScMet.) and rotarod toxicity tests in mice according to the phase I tests of the Antiepileptic Drug Development programme. Compounds I-a, II-a,b,c, III-1b,2a,2c were found protective against MES and III-1b,1c,2a,2c were found protective against ScMet.

Preheated Fly-Ash Catalyzed Cyclization of Chalcones: Synthesis of some Substituted Pyrazole-1-Carbothioamides and Spectral Correlations in 3-(3,4-Dichlorophenyl)-5-(Substituted Phenyl)-4,5-Dihydro-1H-Pyrazole-1-Carbothioamides

“…These solvent free reactions involving the formation of carbon-carbon bond and carbon-heteroatom bond are important and interesting in green synthesis. In the five membered bi-nitrogen heterocyclics, the 1-thiocarbomyl pyrazoline derivatives are important compounds and they possess -CS-NH 2 group in N 1 atom of pyrazoline ring [3,4]. These substituted 1-thiocarbomyl pyrazoline derivatives possess many important biological activities such as, anti-bacterial [5], anti-fungal [5], anti-depressants [7], anti-convulsant [8], anti-inflammatory [9], anti-tumour [10], anaesthetic [11], analgesic [12], anti-cancer [13] MAO-B inhibitors [14], steroidal, nitric oxide synthase inhibitor, anti-viral and cannabinoid CBI receptor antagonists [9].…”

“…These substituted 1-thiocarbomyl pyrazoline derivatives possess many important biological activities such as, anti-bacterial [5], anti-fungal [5], anti-depressants [7], anti-convulsant [8], anti-inflammatory [9], anti-tumour [10], anaesthetic [11], analgesic [12], anti-cancer [13] MAO-B inhibitors [14], steroidal, nitric oxide synthase inhibitor, anti-viral and cannabinoid CBI receptor antagonists [9]. Several solvent-free and thermal methods were reported in literature for synthesis of thiocarbomyl pyrazoline derivatives [3,13,[15][16][17][18]. In these methods, many substituted pyrazoline derivatives were synthesised by cyclization of chalcones with hydrazine hydrate [19] or phenylhydrazine [20] or phenyl hydrazine hydrochloride [21][22][23].…”

“…In these methods, many substituted pyrazoline derivatives were synthesised by cyclization of chalcones with hydrazine hydrate [19] or phenylhydrazine [20] or phenyl hydrazine hydrochloride [21][22][23]. Similarly substituted 1-thiocarbomyl pyrazoline derivatives were synthesised by cyclization of chalcones with thiosemicarbazide [3,13,14,24] or substituted thiosemicarbazide [3,9,14] or hydrazenidium dithiocyanate [25]. In recent years, synthetic organic chemists, scientists and researchers preferred greener synthesis due to easy working procedure, shorter reaction time, higher yields, less hazardousness and solvent usage [26][27][28][29][30][31].…”

“…Several liquid and solid phase catalysts were utilized for synthesis of substituted 1-thiocarbomyl pyrazoline derivatives such as Lewis acids, bases and their salts [13,32,33], CH 3 COOH/CH 3 COONa [3], NaOH/EtOH [24,32,35], KOH/EtOH [20,33], neat reaction in ethanol [3,14] and Basic alumina/ K 2 CO 3 [36,37].…”

Synthesis and Biologic Properties of Some 1-(Alchyl)Phenyl-3-(4-(3-(Pyridin-2-Il)Acryloyl)Phenylthiourea

“…For chalcones with thioureea groups was detected a pronounced antinociceptive activity [14]. The chalcones [15] (with OH, OCH 3 , OCH 2 =CH 2 groups) extracted from Chinese Licorice roots have a strong antileishmanial activity. Robinson et all.…”