RESUMO
A number of 2-([(phenoxy or phenyl)acetyl]amino)benzoic acid derivatives were prepared in about 50% yield from (phenoxy or phenyl)acetyl chloride and anthranilic acid derivatives. All the compounds were tested as in vitro inhibitors of 3 alpha-hydroxysteroid dehydrogenase, since enzyme inhibition predicts potential antiinflammatory activity in vivo. The most active compounds 3 l, m, s are about 3.5 times more active than acetylsalicylic acid (ASA). Activity is influenced by electronic as well as steric effects.
Assuntos
3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Aminobenzoatos/síntese química , Anti-Inflamatórios não Esteroides/síntese química , Inibidores Enzimáticos/síntese química , Aminobenzoatos/farmacologia , Animais , Antibacterianos , Anti-Infecciosos/síntese química , Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Bactérias/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Técnicas In Vitro , Testes de Sensibilidade Microbiana , Ratos , Leveduras/efeitos dos fármacosRESUMO
A number of new 3-(isoxazol-5-yl)-quinazolin-4(3H)-ones was prepared and tested, together a few analogues previously obtained, for their analgesic, antipyretic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effects. In the carrageenan rat foot edema model one of the tested compounds showed activity and LD50 comparable to that of ASA, but the ulceration index approximated zero value.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Isoxazóis/síntese química , Quinazolinas/síntese química , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Comportamento Animal/efeitos dos fármacos , Isoxazóis/farmacologia , Isoxazóis/toxicidade , Masculino , Camundongos , Quinazolinas/farmacologia , Quinazolinas/toxicidade , Ratos , Ratos Sprague-Dawley , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/patologiaRESUMO
Following our research on analgesic and antiinflammatory active compounds containing the pyrazole nucleus, a number of new 1-methyl- or 1-phenyl-6-(2-substitutedphenyl)-pyrazolo[3,4-d]-1,3-oxazin- 4(1H)-ones was synthesized and tested, together with a few analogues previously obtained, for their analgesic and antiinflammatory activities, as well as for their acute toxicity and ulcerogenic effects. One of the tested compounds showed activity comparable to that of phenylbutazone and, at the same time, higher LD50 and a very low ulceration index.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Oxazinas/síntese química , Pirazóis/síntese química , Analgésicos/farmacologia , Analgésicos/toxicidade , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/toxicidade , Comportamento Animal/efeitos dos fármacos , Dose Letal Mediana , Masculino , Camundongos , Oxazinas/farmacologia , Pirazóis/farmacologia , Úlcera Gástrica/induzido quimicamenteRESUMO
Following our research on analgesic and antiinflammatory active compounds containing the pyrazole nucleus, a number of 3-(pyrazol-5-yl)-1,2,3-benzotriazin-4(3H)-ones and quinazolin-4(3H)-ones was synthetized and tested. The results of tests for analgesic, antiexudative and antioedema activities, as well as for induction of lesion in the gastric mucosa, are reported and discussed.
Assuntos
Anti-Inflamatórios não Esteroides/síntese química , Pirazóis/síntese química , Quinazolinas/síntese química , Triazinas/síntese química , Animais , Anti-Inflamatórios não Esteroides/toxicidade , Comportamento Animal/efeitos dos fármacos , Fenômenos Químicos , Química , Exsudatos e Transudatos/efeitos dos fármacos , Dose Letal Mediana , Masculino , Camundongos , Pirazóis/farmacologia , Pirazóis/toxicidade , Quinazolinas/farmacologia , Quinazolinas/toxicidade , Ratos , Ratos Endogâmicos , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/fisiopatologia , Relação Estrutura-Atividade , Triazinas/farmacologia , Triazinas/toxicidadeRESUMO
The attachment of various drugs bearing -NH2 groups to poly-alpha,beta-aspartic acid as a biodegradable carrier afforded in good yields macromolecular prodrugs which were characterized with respect to composition and drug load by spectroscopic and analytical methods. N-Ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) in an aqueous medium proved to be useful in the attachment reaction. Isoniazid, procaine and histamine were covalently coupled as pendant groups onto poly-alpha,beta-aspartic acid via an amide bond. In principle, controlled release of the aforementioned drugs can be achieved by biodegradation of the polymer or by cleavage of covalently bound polymer-drug conjugates.
Assuntos
Histamina/análogos & derivados , Isoniazida/análogos & derivados , Procaína/análogos & derivados , Pró-Fármacos/síntese química , Fenômenos Químicos , Química , Histamina/administração & dosagem , Isoniazida/administração & dosagem , Peso Molecular , Procaína/administração & dosagemRESUMO
Novel N-(3-methyl-4-R-isoxazol-5-yl)-2-R1-4-R2-phenoxyacetamides and N-(3-methyl-4-R-isoxazol-5-yl)-2-(2-R1-4-R2-phenoxyacetamido) benzamides were prepared and tested against Candida albicans and Cryptococcus neoformans. The results of the antimicrobial assay showed that the presence of two amidic groups usually enhances antimycotic activity.
Assuntos
Acetamidas/síntese química , Antifúngicos/síntese química , Acetamidas/farmacologia , Candida albicans/efeitos dos fármacos , Cryptococcus neoformans/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Relação Estrutura-AtividadeRESUMO
A number of new N-pyrazolylsalicylamides were prepared by fusion of phenyl salicylate and aminopyrazoles. The condensation reaction is influenced by the substitution at the C-4 position of the aminopyrazole. All the substances obtained were tested for antifungal activity against Cryptococcus neoformans and Candida albicans. It was found that their fungitoxicity is dependent on the structural feature.
