ChemInform Abstract: Synthesis of Novel Pyrazole Derivatives and Evaluation of Their Antidepressant and Anticonvulsant Activities

Department of Medicinal Chemistry, Faculty of Pharmacy, Minia University, Minia, Egypt.
European Journal of Medicinal Chemistry (Impact Factor: 3.45). 03/2009; 44(9):3480-7. DOI: 10.1016/j.ejmech.2009.01.032
Source: PubMed


Substituted carboxylic acid hydrazides 1a-d reacted with ethenetetracarbonitril 2 in dimethyl formamide with the formation of diacylhydrazines 4a-d and 5-amino-1-substituted pyrazole-3,3,4-tricarbonitriles 5a-d. On the other hand, 1a-d reacted with diethyl (E)-2,3-dicyanobutenedioate 3 to give oxadiazole derivatives 10a-d and pyrazolone derivatives 11a-d, respectively. The prepared compounds 4a-d, 5a-d and 11a-d were evaluated each for antidepressant activity using tail suspension behavioral despair test and anticonvulsant activity against PTZ induced seizures in mice. Compounds 4a and 4b induced markedly antidepressant activity compared to imipramine, and their activities as antidepressant nearly equal twice the activity of imipramine at 10 mg kg(-1) dose level. On the other hand, compounds 11b, 11a and 11d exhibited remarkable protective effect against clonic seizures induced by i.p. injection of PTZ at a dose level of 20 mg kg(-1). The results of anticonvulsant activity are nearly close to phenobarbital sodium at a dose level of 30 mg kg(-1) and more potent than phenytoin sodium at a dose level of 30 mg kg(-1).

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Available from: Gamal El-Din Abuo-Rahma, Apr 22, 2014
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    • "In particular, five and six membered heterocyclic systems are scaffolds of many efficacious drugs. Among these, pyrazole is a versatile aromatic five-membered ring endowed with diverse biological activity on humans such as antimicrobial [1], anti-inflammatory [2], anticancer [3], antiviral [4], anticonvulsant and antidepressant [5]. "
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    ABSTRACT: In this review we report the recent advances in bioactive system containing pyrazole fused with a five membered heterocycle, covering the time span of the last decade. All of them are represented around the common structure of the pyrazole ring fused with another five membered heterocycle containing the nitrogen, sulfur and oxygen atoms in all their possible combinations. The classification we have used is based in terms of the therapeutic area providing, when possible, some general conclusions on the targets and mechanisms of action as well as the structure-activity relationships of the molecules. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
    European Journal of Medicinal Chemistry 12/2014; 97(32). DOI:10.1016/j.ejmech.2014.12.023 · 3.45 Impact Factor
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    • "The pyrazole derivatives play important roles in the development of pesticides and medicines and are found to exhibit a wide range of interesting bioactivities such as anti-inflammatory [5], anti-viral [6], anti-tumor [7], anti-depressant, anti-convulsant [8], antimicrobial [9] and anti-cancer activity [10]. In addition, some pyrazole derivatives are widely used as fungicides, antiviral agents, analgesic agents, insecticides and herbicides [11]. "
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    ABSTRACT: A new series of 1H-pyrazole derivatives 5a–j bearing an aryl sulfonate moiety have been synthesized by a one-pot cyclo-condensation reaction of 2-(3-(dimethylamino)acryloyl)phenyl-4-methyl benzene sulfonates 4a–e and hydrazine hydrate or phenyl hydrazine in ethanol under reflux conditions. Some of the newly synthesized compounds were screened for their anti-inflammatory activity. All synthesized compounds were screened against Gram positive and Gram negative bacterial and fungal strains. The compound 5b was found to be a potent anti-inflammatory agent while the majority of the compounds were found to be active against microbial strains.
    Chinese Chemical Letters 04/2013; 24(4):325–328. DOI:10.1016/j.cclet.2013.02.016 · 1.59 Impact Factor
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    • "Product development involves application of existing products to meet the therapeutic need in addition to the discovery of new drugs. Literature review revealed that many compounds bearing a five membered heterocyclic ring containing nitrogen and oxygen like oxadiazole have been synthesized and showed a variety of biological activities like anticancer (Sengupta et al., 2008; Jin et al., 2006; Holla et al., 2005), anticonvulsant (Almasirad et al., 2004; Aziz et al., 2009), antimicrobial (Shetgiri and Nayak, 2005; Manjunatha et al., 2010; Shailaja et al., 2010; Mulwad and Chaskar, 2006; Ansari and Lal, 2009), anti-inflammatory analgesic (Bhandari et al., 2008; Dewangan et al., 2010; Amir et al., 2007; Kumar et al., 2008; Jayashankar et al., 2009), dyes and pigments (ShuiLv et al., 2010), ulcerogenic (Gilani et al., 2010), antitubercular (Ali and Shaharyar, 2007) etc. "
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    ABSTRACT: In the present study o-phenylenediamine and naphtene-1-acetic acid/2-naphthoxyacetic acid were used as a starting material through a series of steps and 2-(naphthalen-1-ylmethyl/Naphthalen-2-yloxymethyl)-1H-benzimidazol-1-yl]acetohydrazide 5a, 5b were obtained. In the first series 1,3,4-oxadiazole derivatives have been synthesized from Schiff base of the corresponding hydrazide i.e. 2-[2-(naphthalen-1-ylmethyl)-1H-benzimidazol-1-yl]acetohydrazide 5a by using Chloramin-T. In the second series 1,3,4-oxadiazole has been synthesized from 2-{2-[(naphthalen-2-yloxy)-methyl]-1Hbenzimidazol-1-yl}acetohydrazide 5b by using phosphorous oxychloride and aromatic acid. These compounds were evaluated by IR, NMR, Mass spectrometry, elemental analysis and finally in vitro anticancer evaluation was carried out by NCI 60 Cell screen at a single high dose (10–5 M) on various panel/cell lines. One compound 7c was found to be the most active on breast cancer cell line and compounds 4b and 7d were moderately active.
    Arabian Journal of Chemistry 02/2013; 7(4). DOI:10.1016/j.arabjc.2013.02.001 · 3.73 Impact Factor
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