New Benzo[d]thiazol-2-yl-aminoacetamides as Potential Anticonvulsants: Synthesis, Activity and Prediction of Molecular Properties (original) (raw)
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IP Innovative Publication Pvt. Ltd., 2018
Several new promising bioactive derivatives of N-(5-(Substituted)-1, 3, 4-thiadiazol-2-yl)-2-((5-(substitutes)-4H-1, 2, 4-triazol-3-yl) amino) acetamide were synthesized. The compounds were obtained in excellent yields. The synthesized compounds were confirmed on the basis of IR and NMR. Acute toxicity study was done to determine the LD50 of the newly synthesized compounds. Some of the synthesized compounds were evaluated for their anticonvulsant effect by PTZ induced convulsions method. Statistical testing was done by one way ANOVA followed by Dunnett’s test. The compounds D-III showed the highest percentage of protection as compared to PTZ, i.e. 80% at the dose of 20mg/kg among the evaluated compounds compared to control. Keywords: 1, 3, 4-thiadiazole, 1, 2, 4-triazole, Anticonvulsant.
TheScientificWorldJournal, 2014
Keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity, a new series of 3-(2-(substitutedbenzylidene)hydrazinyl)-N-(substituted benzo[d]thiazol-2-yl)-propanamides were synthesized with aromatic hydrophobic aryl ring (A), NH-C=O as hydrogen bonding domain (HBD), nitrogen atom as electron donor (D), and phenyl as distal aryl ring (C). Synthesized compounds were characterized by FTIR, (1)H NMR, (13)C NMR, mass spectroscopy, and elemental analysis. Preliminary in vivo anticonvulsant screening (phase I) was performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Based on anticonvulsant screening results, two compounds, 5h and 5p, were found to be most active; they exhibited activity comparable to standard drugs phenytoin (PHY) and carbamazepine (CBZ). These active compounds were subjected to phase II and phase III screening, where they displayed much higher protecti...
European Journal of Medicinal Chemistry, 2013
INTRODUCTION Epilepsy is the fourth most common neurological problem affecting human population after migrane, stroke and Alzheimer's disease (Epilepsy foundation). Epilepsy belongs to a group of neurological disorders showing neuronal hyperexcitability characterized by recurrent seizures in different parts of the brain [1]. According to WHO, it is estimated that the condition affects approximately 50 million people worldwide, 80 % of which resides in developing countries. Enormous AEDs belonging to different classes are used nowadays to treat epilepsy including phenytoin, carbamazepine, valproic acid, topiramate, gabapentin, felbamate, levetiracetam, etc. [2]. However, the current therapy using the presently available antiepileptic drugs shows limitations viz. insufficient, seizure control, unpredictability of effect and its loss, poor efficacy, inadequate information about the receptors involved, etc. Moreover AEDs do not prevent epilepsy in persons at risk of drug-resistance. Further, long term therapy with these drugs pose an array of side effects which includes but is not limited to drowsiness, ataxia, gastrointestinal disturbances, megaloblasticanaemia and hirsutism [3,4]. Hence there exists the continuous need for the discovery and development of new antiepileptic agents with higher activity, minimal or negligible toxicity and side effects. A number of heterocyclic derivatives possessing nitrogen has been reported to play an important role in pharmaceutical Design, Synthesis and Anticonvulsant Evaluation of N-[(Substituted 1H-pyrazol-3-yl)amino]-2-(4-methylphenyl)quinazolin-4(3H)-one Derivatives
Archiv der Pharmazie, 2009
A series of novel N 1-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N 4-(4-substituted benzaldehyde)semicarbazone 1-12, N 1-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N 4-[1-(4-substituted phenyl)ethanone]-semicarbazone 13-16, and N 1-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N 4-[1-(4-substituted phenyl) (phenyl) methanone]-semicarbazone 17-20 were synthesized for their anticonvulsant activity. The chemical structures of the compounds were proved by elemental and spectral (IR, 1 H-NMR, 13 C-NMR, and MS) analysis. The anticonvulsant potential of the compounds was investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. Compound 19 was found to possess significant anticonvulsant activity in both the models employed for anticonvulsant evaluation. Compounds 8, 13, 15, and 16 also demonstrated a marked anticonvulsant property. The results of the present study validated that the pharmacophore model with four binding sites is essential for anticonvulsant activity. The efforts were also made to establish structure-activity relationships among the synthesized compounds.
Design of Benzothiazole-1,3,4-thiadiazole Conjugates: Synthesis and Anticonvulsant Evaluation
Archiv der Pharmazie, 2013
Various 2-[(6-substituted-1,3-benzothiazol-2-yl)amino]-N-[5-substituted-phenyl-1,3,4-thiadiazol-2-yl]acetamides were synthesized with a prospective exploration of "lead hopping", using pharmacophoric elements for in vivo anticonvulsant activity. This yielded three potent candidates (5i, 5t, and 5u) in the preliminary screening employing the maximal electroshock seizure (MES) and the subcutaneous pentylenetetrazole (scPTZ) test, showing minimal neurotoxicity. Their quantitative study indicated an increase of nearly 2-10 times for the MES test and 7-to 67-fold for the scPTZ test in the protective index, the keystone in drug discovery for anticonvulsant activity.
Acta Pharmaceutica, 2000
The term epilepsy is a collective term that includes disorders of the brain function characterized by the periodic and unpredictable occurrence of seizures. Epilepsies are common and frequently devastating and affect around 1-2 % of the world population (1). Current drug therapy for epilepsy suffers from a number of disadvantages, including the fact that the convulsions of approximately 25 % of epileptics are inadequately controlled by medication (2). In recent years, the field of antiepileptic drug development has become quite dynamic, affording many promising research opportunities. In our previous study (3-5), we designed aryl-substituted semicarbazones with benzothiazole moiety, in which we made some modifications in the structure of semicarbazones. The lipophilic aryl ring was replaced with a versatile heterocyclic molecule ben-441
European Journal of Medicinal Chemistry, 2008
A series of 3-aryl amino/amino-4-aryl-5-imino-Δ2-1,2,4-thiadiazoline have been synthesized using an appropriate synthetic route and characterized by elemental analyses and spectral data. The anticonvulsant activity of all the synthesized compounds was evaluated against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (ScPTZ) induced seizure models in mice. The neurotoxicity was assessed using the rotorod method. All the test compounds were administered
2010
A novel series of N'-{5-[(1H-indol-3-ylmethyl)-1,3,4-thiadiazol-2-yl}-N4-(4-substituted benzaldehyde)-semicarbazones, N1-{5-[(1H-indol-3-ylmethyl)-1,3,4-thiadiazol-2-yl}-N4-[1-(4-substituted phenyl)ethanone]-semicarbazones and N1-{5-[(1H-indol-3-ylmethyl)-1,3,4-thiadiazol-2-yl}-N4-[1-(4-substituted phenyl) (phenyl) methanone]-semicarbazones were synthesized and evaluated for their anticonvulsant potential using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPFZ) models. The minimal motor impairment (neurotoxicity) was determined by rotorod test. The results of the present study confirmed the requirements of various structural features of four binding site pharmacophore model for anticonvulsant activity.
Synthesis, anticonvulsant and toxicity screening of thiazolyl–thiadiazole derivatives
Medicinal Chemistry Research, 2011
Various thiazole-substituted thiadiazole derivatives (7a-t) were designed and synthesized using substituted acetophenones and substituted anilines as starting materials. Thiazole and thiadiazole moieties being anticonvulsants were clubbed together to get the titled compounds and their in vivo anticonvulsant screening were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Three compounds 7i, 7l and 7n were found to be potent in both the screens with comparable ED 50 and better TD 50 values than some standard drugs. These compounds were also found to exert lesser toxic effects on liver.