The Hansch approach was used in the quantitative structure anticonvulsant activity studies of the previously synthesized 1-substituted-and 1.5-disubstituted-3-pyrazo- lidinones.Correlation analysis predicted that 1.5-...The Hansch approach was used in the quantitative structure anticonvulsant activity studies of the previously synthesized 1-substituted-and 1.5-disubstituted-3-pyrazo- lidinones.Correlation analysis predicted that 1.5-disubstituted-3-pyrazoljdinones in which 1- substituent is n-propyl but not benzyl.with the total hydrophobic constant of 1-and 5-sub- stituents(∑л)equals to 4.5(optimum value)will have the most potent activity.On the basis of this analysis eleven 5-substituted and I-n-butyl-5-substituted-3-pyrazolidinones were syn- thesized.Pharmacological tests indicated that the prediction of the Hansch analysis of the 3- pyrazolidinones is correct.The Hansch analysis,by including these 11 compounds,gives an almost identical correlation with that previously obtained.展开更多
In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evalu...In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.展开更多
On the basis of systematic modification of the structure of componds of antiepilepsirine type, more than 200 cinnamamides were synthesized and tested by animal assay (maximal electroshock seizure, MES). Pharmacologica...On the basis of systematic modification of the structure of componds of antiepilepsirine type, more than 200 cinnamamides were synthesized and tested by animal assay (maximal electroshock seizure, MES). Pharmacological evaluation showed that the configuration and the substituents on the phenyl ring and the nitrogen of amides, and substituents on the double bond displayed an important effect on the anticonvulsant activity.For studying the effect of the modification of structure to anticonvulsant activity, Hansch approach was employed to study the QSAR among 38 cinnamamides, and Hopfinger' s MSA was employed to study the MSA-QSAR among 26 cinnamamides.展开更多
Under physiological conditions, γ-aminobutyric acid poorly crosses the blood-brain barrier. It is likely that a non-toxic derivative of γ-aminobutyric acid which enters the brain easily will have useful anticonvulsa...Under physiological conditions, γ-aminobutyric acid poorly crosses the blood-brain barrier. It is likely that a non-toxic derivative of γ-aminobutyric acid which enters the brain easily will have useful anticonvulsant activity. 16 derivatives of γ-aminobutyric acid with an imine link to a lipophilic carrier were prepared and tested for anticonvulsant activity; six compounds show anticonvulsant activity.展开更多
In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a^5f were synthesized by condensation of various benzils 4a^4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and...In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a^5f were synthesized by condensation of various benzils 4a^4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies. Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectroscopic data.展开更多
Crassula arborescens （Mill.） Willd. subsp. Arborescens is widely used for the treatment of various ailments including diarrhoea, corns, epilepsy and as a purgative. However, no information exists in any literature t...Crassula arborescens （Mill.） Willd. subsp. Arborescens is widely used for the treatment of various ailments including diarrhoea, corns, epilepsy and as a purgative. However, no information exists in any literature to verify the acclaimed effectiveness of C. arborescens in the treatment of the various ailments. The study, therefore, intended to investigate the anticonvulsant activity of the leaf methanol extract of C. arborescens in mice. Acute toxicity study and phytochemical qualitative analysis of the plant extracts were also carried out. Chemically-induced convulsion methods were used to assess the anticonvulsant activity of C. arborescens. Standard methods were used for the acute toxicity study and phytochemical analysis of the chemical components of the plant extract. PTZ （pentylenetetrazole）, bicuculline, picrotoxin, NMDLA （N-methyl-DL-aspartic acid） or strychnine produced tonic convulsions in all the mice used. Leaf methanol extract of Crassula arborescens, muscimol, phenobarbitone or diazepam significantly antagonised PTZ, bicuculline or picrotoxin-induced convulsion. C. arborescens or LY233053 significantly antagonised NMDLA-induced tonic convulsion. C. arborescens or phenobarbitone significantly antagonised strychnine-elicited tonic convulsion. Phenytoin or DMSO （dimethylsulfoxide） did not significantly affect the tonic convulsion produced by PTZ, bicuculline, picrotoxin, NMDLA or strychnine. The LDso value obtained from intraperitoneal administration of C. arborescens was 781.6 mg/kg while that following oral administration of the plant extract was over 4,000 mg/kg. The phytochemical qualitative analysis done showed the presence of flavonoids, tannins, reducing sugar, saponins and triterpene steroids. The data obtained in the study show that the leaf methanol extract of Crassula arborescens has anticonvulsant activity which may be underpinned by GABAergic, glutaminergic and glycinergic mechanisms. The high LDso value obtained following the oral administration of the plant extract shows that the leaf methanol extract is non-toxic to animals.展开更多
The present study was designed to investigate the anticonvulsant effect of series phthalimides possessing an N-aromatic amines moiety substituted at position 2 （2-7）. The compounds synthesized using phthalic anhydri...The present study was designed to investigate the anticonvulsant effect of series phthalimides possessing an N-aromatic amines moiety substituted at position 2 （2-7）. The compounds synthesized using phthalic anhydride and various amines in reflux synthesizer. The chemical structures of the titled compound were confirmed by physical and spectra analysis. All the synthesized compounds were evaluated in vivo for antiepileptic activity by using standard experimental models. Compounds： 2-（3H-1, 2, 4-Triazole-3-y） isoindoline-1, 3-dione （2）, Ethyl-4（1, 3-dioxoisoindoline-2-yl） benzoate 3 and 2-（4-nitrophenyl） isoindoline-1,3dione （7） were found significantly （P 〈 0.01-0.00001） delayed the onset and antagonized picrotoxin-induced seizures.展开更多
In pursuit for better antiepileptic drug and the importance of semicarbazones and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore, a series of novel N-（{5-[（6-methyl-l-benzofuran-3-yl）methyl]-l...In pursuit for better antiepileptic drug and the importance of semicarbazones and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore, a series of novel N-（{5-[（6-methyl-l-benzofuran-3-yl）methyl]-l,3,4-thiadiazol-2-yl}carba- mothioyl）-2/3/4-substitutedbenzamide were designed, synthesized and evaluated for their anticonvulsant activity. The findings of the present studies confirmed that the pharmacophore model with four binding sites is crucial for anticonvulsant activity. Structure-activity relationships among synthesized compounds were also established.展开更多
Melting point (T_m), melting enthalpy (△H_m), melting entropy (△S_m) are important thermodynamic parameters of compounds. The thermodynamic parameters of a series of β-substituted para-chlorocinnamamides were first...Melting point (T_m), melting enthalpy (△H_m), melting entropy (△S_m) are important thermodynamic parameters of compounds. The thermodynamic parameters of a series of β-substituted para-chlorocinnamamides were first reported in this note. Cinnamamides display a variety of pharmacological actions. The relationship between their structure and anticonvulsant activity in particular has been studied extensively. Literature reported that the partition coefficient (log p, octanol/water), dipole moment and inductive effect index (Ⅰ) of the compounds,展开更多
In order to investigate the relationship between structure and the activity of cinnamyl-isobutylamuine,the ab initio calculation was undertaken and the information of their electronic sturctures was obtained.It is fou...In order to investigate the relationship between structure and the activity of cinnamyl-isobutylamuine,the ab initio calculation was undertaken and the information of their electronic sturctures was obtained.It is found that the anticonvulsant activities of these kinds of compounds have a linear relationship with energy and composition of LUMO and LUMO(+3).When the drug molecule interacts with the acceptor,there may be occurrence of electron transfer between the drug molecule and the acceptor to form the electron-transferred-complex.The active sites of the drug molecule are at the carbony and ethylene bond.展开更多
文摘The Hansch approach was used in the quantitative structure anticonvulsant activity studies of the previously synthesized 1-substituted-and 1.5-disubstituted-3-pyrazo- lidinones.Correlation analysis predicted that 1.5-disubstituted-3-pyrazoljdinones in which 1- substituent is n-propyl but not benzyl.with the total hydrophobic constant of 1-and 5-sub- stituents(∑л)equals to 4.5(optimum value)will have the most potent activity.On the basis of this analysis eleven 5-substituted and I-n-butyl-5-substituted-3-pyrazolidinones were syn- thesized.Pharmacological tests indicated that the prediction of the Hansch analysis of the 3- pyrazolidinones is correct.The Hansch analysis,by including these 11 compounds,gives an almost identical correlation with that previously obtained.
文摘In searching for effective anticonvulsant agents,fourteen 6-aryl-4.5-di- hydro-3(2H)pyridazinones.fifteen 6-aryl-3(2H)pyridazinones,and seventeen 3-GABA derivatives of 6-aryIpyridazines have been synthesized,and evaluated in mice for the ability to antagonize maximal electroshock seizure(MES).The ED_(50) values showed that 6-(2′,4′- dichlorophenyt)-3(2H)pyridazinone was the most potent anticonvulsant among these corn- pounds(ED_(50)=10.15 mg/kg).The structure-activity relationships of the aryl pyridazinones were studied.The result showed that:(1)the higher the value of the hydrophobic parameter л of the substituent on the phenyl ring.the more potent the anticonvulsant activity of the corn- pound.and(2)only the compounds with an electron withdrawing substituent on the phenyl ring exhibited appreciable anticonvulsant activity.
基金Projects Supported by the National Fund of Natural Sciences
文摘On the basis of systematic modification of the structure of componds of antiepilepsirine type, more than 200 cinnamamides were synthesized and tested by animal assay (maximal electroshock seizure, MES). Pharmacological evaluation showed that the configuration and the substituents on the phenyl ring and the nitrogen of amides, and substituents on the double bond displayed an important effect on the anticonvulsant activity.For studying the effect of the modification of structure to anticonvulsant activity, Hansch approach was employed to study the QSAR among 38 cinnamamides, and Hopfinger' s MSA was employed to study the MSA-QSAR among 26 cinnamamides.
文摘Under physiological conditions, γ-aminobutyric acid poorly crosses the blood-brain barrier. It is likely that a non-toxic derivative of γ-aminobutyric acid which enters the brain easily will have useful anticonvulsant activity. 16 derivatives of γ-aminobutyric acid with an imine link to a lipophilic carrier were prepared and tested for anticonvulsant activity; six compounds show anticonvulsant activity.
文摘In the present research, a series of 5,6-bis aryl 1,2,4-triazines 5a^5f were synthesized by condensation of various benzils 4a^4f with aminoguanidine bicarbonate and were screened in vivo, for their anticonvulsant and neurotoxicity studies. Compounds 5a, 5b and 5d were found to be potent molecules of this series, when compared with the reference drugs phenytoin sodium, diazepam and lamotrigine. The structures of these compounds were established by IR, 1H NMR, 13C NMR and mass spectroscopic data.
文摘Crassula arborescens （Mill.） Willd. subsp. Arborescens is widely used for the treatment of various ailments including diarrhoea, corns, epilepsy and as a purgative. However, no information exists in any literature to verify the acclaimed effectiveness of C. arborescens in the treatment of the various ailments. The study, therefore, intended to investigate the anticonvulsant activity of the leaf methanol extract of C. arborescens in mice. Acute toxicity study and phytochemical qualitative analysis of the plant extracts were also carried out. Chemically-induced convulsion methods were used to assess the anticonvulsant activity of C. arborescens. Standard methods were used for the acute toxicity study and phytochemical analysis of the chemical components of the plant extract. PTZ （pentylenetetrazole）, bicuculline, picrotoxin, NMDLA （N-methyl-DL-aspartic acid） or strychnine produced tonic convulsions in all the mice used. Leaf methanol extract of Crassula arborescens, muscimol, phenobarbitone or diazepam significantly antagonised PTZ, bicuculline or picrotoxin-induced convulsion. C. arborescens or LY233053 significantly antagonised NMDLA-induced tonic convulsion. C. arborescens or phenobarbitone significantly antagonised strychnine-elicited tonic convulsion. Phenytoin or DMSO （dimethylsulfoxide） did not significantly affect the tonic convulsion produced by PTZ, bicuculline, picrotoxin, NMDLA or strychnine. The LDso value obtained from intraperitoneal administration of C. arborescens was 781.6 mg/kg while that following oral administration of the plant extract was over 4,000 mg/kg. The phytochemical qualitative analysis done showed the presence of flavonoids, tannins, reducing sugar, saponins and triterpene steroids. The data obtained in the study show that the leaf methanol extract of Crassula arborescens has anticonvulsant activity which may be underpinned by GABAergic, glutaminergic and glycinergic mechanisms. The high LDso value obtained following the oral administration of the plant extract shows that the leaf methanol extract is non-toxic to animals.
文摘The present study was designed to investigate the anticonvulsant effect of series phthalimides possessing an N-aromatic amines moiety substituted at position 2 （2-7）. The compounds synthesized using phthalic anhydride and various amines in reflux synthesizer. The chemical structures of the titled compound were confirmed by physical and spectra analysis. All the synthesized compounds were evaluated in vivo for antiepileptic activity by using standard experimental models. Compounds： 2-（3H-1, 2, 4-Triazole-3-y） isoindoline-1, 3-dione （2）, Ethyl-4（1, 3-dioxoisoindoline-2-yl） benzoate 3 and 2-（4-nitrophenyl） isoindoline-1,3dione （7） were found significantly （P 〈 0.01-0.00001） delayed the onset and antagonized picrotoxin-induced seizures.
文摘In pursuit for better antiepileptic drug and the importance of semicarbazones and 2,5-disubstituted 1,3,4-thiadiazoles as anticonvulsant pharmacophore, a series of novel N-（{5-[（6-methyl-l-benzofuran-3-yl）methyl]-l,3,4-thiadiazol-2-yl}carba- mothioyl）-2/3/4-substitutedbenzamide were designed, synthesized and evaluated for their anticonvulsant activity. The findings of the present studies confirmed that the pharmacophore model with four binding sites is crucial for anticonvulsant activity. Structure-activity relationships among synthesized compounds were also established.
文摘Melting point (T_m), melting enthalpy (△H_m), melting entropy (△S_m) are important thermodynamic parameters of compounds. The thermodynamic parameters of a series of β-substituted para-chlorocinnamamides were first reported in this note. Cinnamamides display a variety of pharmacological actions. The relationship between their structure and anticonvulsant activity in particular has been studied extensively. Literature reported that the partition coefficient (log p, octanol/water), dipole moment and inductive effect index (Ⅰ) of the compounds,
文摘In order to investigate the relationship between structure and the activity of cinnamyl-isobutylamuine,the ab initio calculation was undertaken and the information of their electronic sturctures was obtained.It is found that the anticonvulsant activities of these kinds of compounds have a linear relationship with energy and composition of LUMO and LUMO(+3).When the drug molecule interacts with the acceptor,there may be occurrence of electron transfer between the drug molecule and the acceptor to form the electron-transferred-complex.The active sites of the drug molecule are at the carbony and ethylene bond.
