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ABSTRACT: A new series of thiazolo [3,2-a] pyrimidine derivatives was designed and synthesized using 4-fluoroaniline and ethylacetoacetate
as starting material. Anti-inflammatory activity was assessed by the rat paw edema method and antinociceptive activity was
evaluated by thermal stimulus technique. The compounds 5-(4-chlorophenyl)-2-(4-fluorobenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3l) and 2-(4-chlorobenzylidene)-5-(4-fluorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3q) were found to possess significant anti-inflammatory and antinociceptive activities. These compounds also showed lower ulcerogenic
activity and higher ALD50 values. Compounds with an aryl ring substituted with a smaller electron withdrawing group at the fourth position displayed
better activity than the other derivatives.
KeywordsThiazolopyrimidine-Anti-inflammatory-Antinociceptive-Acute toxicity
Medicinal Chemistry Research 04/2012; 19(9):1245-1258. · 1.27 Impact Factor
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ABSTRACT: 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 ED50 and better TD50 values than some standard drugs. These compounds were also found to exert lesser toxic effects on liver.
KeywordsThiazole–Thiadiazole–Anticonvulsant activity–Neurotoxicity–Hepatotoxicity
Medicinal Chemistry Research 04/2012; 20(2):261-268. · 1.27 Impact Factor
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ABSTRACT: A number of N-(4,6-substituted diphenylpyrimidin-2-yl) semicarbazones (4a–t) were synthesized and tested for their anticonvulsant activity against the two seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). All the synthesized compounds possessed the four essential pharmacophoric elements for good anticonvulsant activity. Most of the compounds displayed good anticonvulsant activity with lesser neurotoxicity. To assess the unwanted effects of the compounds on liver, estimation of enzymes and proteins was carried out.Graphical abstractVarious pyrimidine incorporated semicarbazones (4a–t) have been synthesized keeping in view the structural requirements of the proposed pharmacophore model. Some compounds showed promising anticonvulsant activity with less neurotoxicity and hepatotoxicity.
European Journal of Medicinal Chemistry. 04/2012; 45(6):2467-2472.
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ABSTRACT: Various 1-[6-(4-substituted phenyl)-3-cyano-4-(substituted phenyl)-pyridin-2-yl]-5-oxopyrrolidine-3-carboxylic acids (3a-t) were designed and synthesized by clubbing pyrrolidinones and pyridines, the two active anticonvulsant pharmacophores. All the synthesized compounds fulfilled the requirements of suggested pharmacophoric model for anticonvulsant activity. Their in vivo anticonvulsant evaluation was performed by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. The minimal motor impairment was assessed by rotorod test and the estimation of various liver enzymes was performed to check the magnitude of liver toxicity posed by the synthesized compounds. Compounds 3d and 3k displayed comparable anticonvulsant activity to the standard drugs with ED(50) values of 13.4 and 18.6 mg/kg in electroshock screen, repectively. The compounds 3d and 3k were also found to have encouraging anticonvulsant activity (ED(50) = 86.1 and 271.6 mg/kg, respectively) in scPTZ screen. Interestingly, they did not show any sign of motor impairment at the maximum dose administered and were not toxic to the liver.
Archiv der Pharmazie 03/2012; 345(3):185-94. · 1.71 Impact Factor
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ABSTRACT: The use of current antiepileptic drugs has been questioned due to the nonselectivity of the drugs and the undesirable side effects posed by them. This led to an intensive investigation in this area worldwide during the past 10 years. There have been some significant outcomes and the findings are promising as far as drug efficacy and safety is concerned. This review covers the new anticonvulsant agents that have shown encouraging activities and less neurotoxicity. A detailed pharmacology and pathophysiology of different types of epilepsy is described here with the structural classification of most active agents. The new structural classes of compounds may prove as lead molecules and good candidates for the future investigations.
Current topics in medicinal chemistry 02/2012; 12(9):1072-92. · 4.47 Impact Factor
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ABSTRACT: A number of 5-(4-substituted phenyl)-2-(substituted benzylsulfanyl)-4-(substituted phenyl)-6-methyl-1,4-dihydro-5-pyrimidine carboxamides (1-30) were designed and synthesized keeping in view the structural requirements as suggested in the pharmacophore model for antihypertensive activity. All the synthesized compounds were tested for antihypertensive activity by non-invasive blood pressure (NIBP) measurements (tail-cuff method) in rats. Almost all the tested compounds displayed considerable decrease in the blood pressure as compared to control. Thirteen compounds showed significant antihypertensive activity comparable to the standard drug nifedipine.
European journal of medicinal chemistry 11/2010; 45(11):5113-9. · 3.27 Impact Factor
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ABSTRACT: A series of (Z)-2-(substituted aryl)-N-(3-oxo-4-(substituted carbamothioyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl) hydrazine carboxamides (6a-r) was synthesized using 2-amino-5-nitrophenol as a starting material. All the synthesized compounds possessed two hydrogen-bonding domains and their effect on the activity was studied thereof. The anticonvulsant activity was assessed by the maximal electroshock test (MES), subcutaneous pentylenetetrazole test (scPTZ) and intraperitoneal thiosemicarbazide test (ipTSC). Compounds (6b, 6h, 6i, and 6p) were found to be the most potent of the series as they showed 83-100% protection in the MES test. They also displayed considerable activity in the chemically induced seizure tests. Most of the tested compounds were devoid of the neurotoxic and hepatotoxic effects.
Archiv der Pharmazie 11/2010; 343(11-12):657-63. · 1.71 Impact Factor
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ABSTRACT: Various 3-[4-(substituted phenyl)-1,3-thiazol-2-ylamino]-4-(substituted phenyl)-4,5-dihydro-1H-1,2,4-triazole-5-thiones (7a-t) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Thiazole and triazole 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). Two compounds 7d and 7f showed significant anticonvulsant activity in both the screens with ED(50) values 23.9 mg/kg and 13.4 mg/kg respectively in MES screen and 178.6 mg/kg and 81.6 mg/kg respectively in scPTZ test. They displayed a wide margin of safety with Protective index (PI), median hypnotic dose (HD(50)) and median lethal dose (LD(50)) much higher than the standard drugs.
European journal of medicinal chemistry 04/2010; 45(4):1536-43. · 3.27 Impact Factor
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ABSTRACT: A series of 4-thiazolidinones bearing a sulfonamide group (4a-w) were prepared by cyclizing various 5-bromo-2-methoxy-N'-[(1E)-arylmethylene/arylethylidene]benzenesulfonohydrazides. All the compounds were characterized by IR, (1)H NMR, and elemental analysis. The compounds were tested for their anticonvulsant activity utilizing MES and scPTZ animal models. The majority of the compounds exhibited significant activity against both animal models; however, compounds 4c, 4m, and 4o displayed promising activity and could be considered as leads for further investigations.
Journal of Enzyme Inhibition and Medicinal Chemistry 03/2010; 25(4):485-91. · 1.62 Impact Factor
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ABSTRACT: A number of N-(4,6-substituted diphenylpyrimidin-2-yl) semicarbazones (4a-t) were synthesized and tested for their anticonvulsant activity against the two seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). All the synthesized compounds possessed the four essential pharmacophoric elements for good anticonvulsant activity. Most of the compounds displayed good anticonvulsant activity with lesser neurotoxicity. To assess the unwanted effects of the compounds on liver, estimation of enzymes and proteins was carried out.
European journal of medicinal chemistry 02/2010; 45(6):2467-72. · 3.27 Impact Factor
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ABSTRACT: A number of new 8-substituted-4-(2/4-substituted phenyl)-2H-[1,3,5]triazino[2,1-b][1,3]benzothiazole-2-thiones (4a-t) were synthesized and evaluated for their anticonvulsant, anti-nociceptive, hepatotoxic, and neurotoxic properties. The titled compounds (4a-t) were obtained by cyclization of N-{[6-substituted-1,3-benzothiazol-2-yl)amino]carbonothioyl}-2/4-substituted benzamides (3a-t) by refluxing in n-butanol. All the newly synthesized compounds were screened for their anticonvulsant activity in a mouse seizure model and were compared with the standard drug phenytoin. Compounds 4a, 4c, 4f, and 4l showed complete protection after time periods of 0.5 h and 4 h. Some of the selected compounds were evaluated for their neurotoxic and hepatotoxic effects, and none of these showed any sign of neurotoxicity or hepatotoxicity. Compounds 4a-t were also evaluated for their anti-nociceptive activity by a thermal stimulus technique using diclofenac as standard. Compounds 4o, 4q, and 4t displayed highly potent analgesic activity with p < 0.01.
Journal of Enzyme Inhibition and Medicinal Chemistry 12/2009; 24(6):1344-50. · 1.62 Impact Factor
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ABSTRACT: Various N-(5-chloro-6-substituted-benzothiazol-2-yl)-N'-(substituted phenyl)-[1,3,4]thiadiazole-2,5-diamines (5a-t) were designed and synthesized starting from substituted acetophenones. Structures of all the compounds were confirmed on the basis of spectral and elemental analyses. All the newly synthesized compounds were screened for their anticonvulsant activity and were compared with the standard drug phenytoin sodium. Interestingly, all the compounds showed protections against seizures in the range 50-100% indicative of the promising nature of the compounds against seizure spread. Compounds 5b and 5c showed complete protection against MES induced seizures.
Acta Pharmaceutica 12/2009; 59(4):441-51. · 0.91 Impact Factor
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ABSTRACT: A series of 1-(6-substituted-1,3-benzothiazol-2-yl)-3-(substituted phenyl)hexahydro-2,4,6-pyrimidinetriones 4a-t were synthesized starting from substituted anilines. These compounds contained two active anticonvulsant pharmacophores, benzothiazole and barbituric acid. Structures of the compounds were confirmed on the basis of different spectroscopic techniques. All the compounds were evaluated for their anticonvulsant activity. Three compounds 4c, 4d, and 4s showed promising anticonvulsant activities in Maximal Electroshock Seizure test (MES) and subcutaneous pentylenetetrazole test (scPTZ). They also displayed a wide safety profile when tested for the minimal motor impairment test.
Archiv der Pharmazie 07/2009; 342(8):462-8. · 1.71 Impact Factor
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ABSTRACT: Various 3,5-(substituted diphenyl)-4,5-dihydro-pyrazole-1-carbothioic acid phenylamides were synthesized starting from substituted acetophenones. Structures of the compounds were confirmed on the basis of spectral data. The compounds were evaluated for their anticonvulsant and antidepressant activity. Interestingly, out of 26 compounds, four (3f, 3g, 3t, and 3u) were found to protect 100% of the animals in the MES screen at a dose of 25 mg/kg. They were also found to have appreciable anticonvulsant activity in scPTZ screen. Two compounds, 3j and 3o, significantly reduced the duration of the immobility time at 25 mg/kg dose, when compared to control.
Archiv der Pharmazie 03/2009; 342(3):173-81. · 1.71 Impact Factor
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ABSTRACT: A series of new 5-(1H-indol-3-yl)methyl-4-(substituted aryl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (4a-g), 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-oxadiazol-2-amines (5a-g) and 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-thiadiazol-2-amines (6a-g) were prepared by treating 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl) hydrazine carbothioamides (3a-g) with suitable reagents. All the newly synthesized compounds were screened for their anticonvulsant activity in the MES model and were compared with the standard drugs phenytoin sodium and carbamazepine. Out of the twenty-one compounds studied, 4b, 4e, 4f, 5b, 5d, 5g, 6b, 6d and 6e showed comparable MES activity to phenytoin and carbamazepine after 0.5 h. Compound 5b showed to be more potent than carbamazepine after 4 h. Compounds 4a, 4c, 4d, 5a, 5c, 5e, 5f, 6f and 6g showed lower neurotoxicity than phenytoin.
Acta Pharmaceutica 01/2009; 58(4):445-54. · 0.91 Impact Factor
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ABSTRACT: A series of new 5-(1H-indol-3-yl)methyl-4-(substituted aryl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones (4a-g), 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-oxadiazol-2-amines (5a-g) and 5-(1H-indol-3-yl)methyl-N-(substituted aryl)-1,3,4-thiadiazol-2-amines (6a-g) were prepared by treating 2-(1H-indol-3-yl)acetyl-N-(substituted phenyl)hydrazine carbothioamides (3a-g) with suitable reagents. All the newly synthesized compounds were screened for their anticonvulsant activity in the MES model and were compared with the standard drugs phenytoin sodium and carbamazepine. Out of the twenty-one compounds studied, 4b, 4e, 4f, 5b, 5d, 5g, 6b, 6d and 6e showed comparable MES activity to phenytoin and carbamazepine after 0.5 h. Compound 5b showed to be more potent than carbamazepine after 4 h. Compounds 4a, 4c, 4d, 5a, 5c, 5e, 5f, 6f and 6g showed lower neurotoxicity than phenytoin.
Acta pharmaceutica (hfd-fg-ap@zg.htnet.hr); Vol.58 No.4.
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ABSTRACT: Various N,N'-diaryl-1,3-thiazole-2,4-diamines (3a-w) were synthesized by a three steps process. The structures of the synthesized compounds were confirmed by spectral data and elemental analyses. All the synthesized compounds were tested against two bacterial strains and two fungal strains. Bacterial strains included Gram positive Staphylococcus aureus and Gram negativeve Escherichia coli and fungal strains included Monascus purpurea and Penicillium citrinum. Most of the compounds showed moderate to good antibacterial as well as antifungal activity.
Acta poloniae pharmaceutica 67(3):239-46. · 0.66 Impact Factor
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ABSTRACT: A series of 5-carbomethoxybenzoxazole derivatives (6a-t) were prepared by using methyl-p-hydroxybenzoate. The identity of the compounds was confirmed on the basis of their elemental analysis and spectral data. In anti-MES test compounds 6b, 6d, 6h, 6j, 6m, 6p, 6q and 6s showed potent activity parallel to lipophilicity. Compounds 6b, 6d, 6k, 6n and 6s successfully passed the rotorod test without any sign of neurological deficit.
Acta poloniae pharmaceutica 65(4):449-55. · 0.66 Impact Factor
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ABSTRACT: A series of 5,6-dimethoxy-2-{1-[arylamino/alkylamino(thioxo)methyl]-4-piperidyl-methyl}-1-indanones (4a–l) were designed and synthesized by the reaction of 5,6-dimethoxy-2-(piperidin-4-yl-methyl)-indan-1-one with aryl/alkyl isothiocyanates.
The anticonvulsant activity was evaluated in animal models by maximal electroshock seizure and subcutaneous pentylenetetrazole
tests. The neurotoxic effects were assessed by rotorod and ethanol potentiation tests. Gamma amino butyric acid (GABA) estimation
of the selected compounds was performed in rat brain utilizing UV absorbance data. Compounds 4d, 4g, and 4j displayed encouraging anticonvulsant profile against both seizure models with remarkably lower neurotoxicity. These compounds
were found to increase the GABA level in rat brain significantly.
Medicinal Chemistry Research - MED CHEM RES.
