RESUMO
5-Ethoxalyl 4-methyl-1H-2,3,4,5-tetrahydro 1,5-benzodiazepin-2 -one [I] and 5-ethoxymalonyl-4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepi n-2-one [IV] were subjected to transesterification using alcohols (propanol, butanol, pentanol) giving derivatives II-IV, VII, VIII. The derivatives I and VI were caused to undergo ammonolysis giving 4-methyl-5-oxamoyl-1H-2,3,4,5 tetrahydro 1,5-benzodiazepin-2-one [V] and 5-malonamoyl-4-methyl-1H-2,3,4,5-tetrahydro-1,5-benzodiazepin++ +-2-one [IX]. The compounds I-IX were tested towards their psychotropic activity. The preparates I, III and V had an anxiolytic action in the four-plate test. The anxiolytic properties of the compound V were confirmed in the test of the black-white box. The antagonism of all investigated compounds for toward reserpine, first of all of the preparations III, IV, V and IX, indicates an antidepressive activity dependent on a stimulation of the adrenergic system.
Assuntos
Ansiolíticos/síntese química , Benzodiazepinonas/síntese química , Animais , Benzodiazepinonas/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Feminino , Dose Letal Mediana , Masculino , Camundongos , Ratos , Ratos WistarRESUMO
Synthesis of new isoxazolo[4,5-d]pyrimidine derivatives is reported. Some of isoxazolo[4,5-d]pyrimidine derivatives were tested for anticonvulsant, anxiolytic and antiserotonine activity. Compounds 14 and 16 proved active against hypothermia induced by reserpine and hyperthermia induced by m-CPP.
Assuntos
Isoxazóis/síntese química , Psicotrópicos/síntese química , Pirimidinas/síntese química , Animais , Ansiolíticos/farmacologia , Anticonvulsivantes/farmacologia , Temperatura Corporal/efeitos dos fármacos , Eletrochoque , Feminino , Isoxazóis/farmacologia , Isoxazóis/toxicidade , Dose Letal Mediana , Masculino , Camundongos , Medição da Dor/efeitos dos fármacos , Pentilenotetrazol/antagonistas & inibidores , Piperazinas/antagonistas & inibidores , Psicotrópicos/farmacologia , Psicotrópicos/toxicidade , Pirimidinas/farmacologia , Pirimidinas/toxicidade , Ratos , Reserpina/antagonistas & inibidores , Reserpina/farmacologia , Agonistas do Receptor de Serotonina/farmacologiaRESUMO
2-Thioxo-1H-2,3,4,5-tetrahydropyrido[2,3-e]-1,3,4-triazep in -5-ones [I] and 2-thioxo-1H-2,3,4,-5-tetrahydro-1,3,4-benzotriazepin-5-ones [V] furnish with methyl, ethyl and phenyl chloroformates two series of the corresponding 3-methoxy-, ethoxy- and phenoxycarbonyl triazepines. In the pharmacological screening, compounds [I], [V] and [II] showed an antianxiety activity in the four plate test, compounds [II] and [III] inhibited the 5-HTP- induced head twitches, and compound [VI] showed an analgesic activity in the "writing" test. The replacement of the benzene ring by the pyridine one in triazepines is accompanied by the enhancement of anxiolytic activity as well as toxicity.
Assuntos
Analgésicos/síntese química , Ansiolíticos/síntese química , Analgésicos/farmacologia , Analgésicos/toxicidade , Animais , Ansiolíticos/farmacologia , Ansiolíticos/toxicidade , Feminino , Dose Letal Mediana , Masculino , Camundongos , Ratos , Ratos Wistar , Relação Estrutura-AtividadeRESUMO
Acylated derivatives of 4-methyl-1H-tetrahydro-1,5-benzodiazepin-2-one (1) and of 2-methyl-4-phenyl-1H-tetrahydro-1,5-benzodiazepino-2-carboxylic acid ethyl ester (10) were synthesized and preliminarily tested on their central activity. Acylation was carried out with alpha, beta-unsaturated acid chlorides, dicarboxylic acid monoester monochlorides, and dicarboxylic acid dichlorides. Compounds 2, 3, 11 and 12 had analgesic, compounds 4, 11 and 12--anticonvulsant, and compounds 3 and 11--antiaggressive properties.
Assuntos
Benzodiazepinas/química , Convulsões/tratamento farmacológico , Acilação , Animais , Benzodiazepinas/farmacologia , Benzodiazepinas/toxicidade , Feminino , Temperatura Alta , Masculino , Camundongos , Pentilenotetrazol/farmacologia , Ratos , Ratos Endogâmicos , Convulsões/induzido quimicamenteRESUMO
In reactions of 1-phenyl-7-methyl-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimido[ 4,5-d]pyrimidin e (1) with 1-(3-chloropropyl)-4-methyl(phenyl, 3-chlorophenyl, 2-pyrimidynyl, 2-thiazolyl)piperazines (5), mixtures of isomeric N- and S-substituted derivatives of compound 1 (3 and 4) were obtained. Isomers were separated by fractional crystallization. The structure of novel compounds 3 and 4 was confirmed by elemental and spectral analyses. In pharmacological screening compounds 3b and 4b displayed rather strong analgesic action, inhibited amphetamine hyperactivity and abolished apomorphine stereotypy. Compounds 3e,3d and 4e attenuated m-chlorophenylpiperazine-induced hypothermia.
Assuntos
Piperazinas/síntese química , Psicotrópicos/síntese química , Pirimidinonas/síntese química , Analgésicos/farmacologia , Animais , Anticonvulsivantes/farmacologia , Antidepressivos/farmacologia , Antiparkinsonianos/síntese química , Antiparkinsonianos/farmacologia , Antipsicóticos/síntese química , Antipsicóticos/farmacologia , Apomorfina/farmacologia , Temperatura Corporal/efeitos dos fármacos , Dextroanfetamina/antagonistas & inibidores , Eletrochoque , Feminino , Isomerismo , Dose Letal Mediana , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Piperazinas/farmacologia , Piperazinas/toxicidade , Psicotrópicos/farmacologia , Psicotrópicos/toxicidade , Pirimidinonas/farmacologia , Pirimidinonas/toxicidade , Ratos , Ratos Endogâmicos , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Several new alpha-aminoderivatives of gamma-(p-chlorophenyl)-tetrahydrofuran-2-one were synthesized. alpha-Aminoderivatives of beta-(p-chlorobenzoyl)-propionic acid 2-13 were used as the substrates. After the reduction with NaBH4 at 10-12 degrees C and cyclization the compounds were converted into the appropriate derivatives of tetrahydrofuran-2-one 16-26. In pharmacological tests compounds 9 and 26 abolished the aggressiveness in isolated mice while compound 8 showed antiinflammatory activity.
Assuntos
Agressão/efeitos dos fármacos , Anti-Inflamatórios não Esteroides/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Furanos/farmacologia , Analgésicos/farmacologia , Animais , Anti-Inflamatórios , Anticonvulsivantes/farmacologia , Pressão Sanguínea/fisiologia , Antagonistas de Dopamina , Feminino , Furanos/síntese química , Furanos/toxicidade , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Ratos , Ratos Endogâmicos , Reserpina/antagonistas & inibidores , Antagonistas da Serotonina/farmacologia , Espectrofotometria InfravermelhoRESUMO
In reaction of alpha-phenyl, alpha-p-chlorophenyl and alpha-m-chlorophenylsuccinic acid with various aminopyridines, N-pyridyl-substituted succinimides (compounds 1-14) were obtained. These compounds were investigated for their CNS activity. Compounds 1, 2, 5, 6 and 7 displayed anticonvulsant properties in the maximum electroshock test. Compounds 5 and 6 were also active in the pentetrazole test.
Assuntos
Anticonvulsivantes/síntese química , Pirimidinas/síntese química , Succinatos/síntese química , 5-Hidroxitriptofano/antagonistas & inibidores , Animais , Antidepressivos/síntese química , Cromatografia em Camada Fina , Sinergismo Farmacológico , Eletrochoque , Feminino , Hexobarbital/farmacologia , Dose Letal Mediana , Levodopa/farmacologia , Masculino , Camundongos , Pentilenotetrazol/antagonistas & inibidores , Pirimidinas/química , Pirimidinas/farmacologia , Antagonistas da Serotonina/síntese química , Sono/efeitos dos fármacos , Succinatos/química , Succinatos/farmacologiaRESUMO
Using 3-cyano-5-(p-chlorophenyl)-tetrahydrofuran-2-one 4, 3-aminomethyl derivatives of 5-(p-chlorophenyl)-tetrahydrofuran-2-one were synthesized. The starting material under alkaline hydrolysis yielded 5-(p-chlorophenyl)-tetrahydrofuran-2-one-3-carboxylic acid 5, which was transformed, via an acid chloride, into amide 6. From acid 5 by aminomethylation compounds 7-12 were obtained. Some of them (7, 8, 12) in reactions of ammono-, amino-, and hydrazinolysis yielded corresponding derivatives of 2-aminomethyl-4-(p-chlorophenyl)-4-hydroxybutyric acid 13-20. In pharmacological tests compounds 10 displayed analgesic activity while compounds 2 and 3 revealed anxiolytic properties.
Assuntos
Depressores do Sistema Nervoso Central/síntese química , Furanos/síntese química , Fenilbutiratos/síntese química , Analgésicos , Animais , Anticonvulsivantes , Apomorfina/antagonistas & inibidores , Pressão Sanguínea/efeitos dos fármacos , Fenômenos Químicos , Química , Feminino , Furanos/farmacologia , Espectroscopia de Ressonância Magnética , Masculino , Camundongos , Fenilbutiratos/farmacologia , Ratos , Ratos Endogâmicos , Reserpina/antagonistas & inibidores , Convulsões/prevenção & controle , Antagonistas da Serotonina , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Sixteen new heterocyclic 1,5-benzodiazepine derivatives (compounds AN8-AN24) were screened for their central action. Compounds AN8-AN10 and AN17 strongly antagonized the action of pentetrazol, compounds AN10, AN14-AN17 and AN22 had potent antiserotonin properties, and compounds AN10, AN19, AN20 and AN23 markedly potentiated the action of DOPA.