RESUMO
New analogues (compounds 6, 7 and 9) of the mono- (8) and diphosphate (10) bioactive forms of the antiherpes drug acyclovir are described. In compound 6, the monophosphate moiety of 8 was replaced by an aminosulfonyloxy group, while in compounds 7 and 9, a phosphonoacetamidoxy and an O-ethyl phosphonoacetamidoxy moiety are, respectively present instead of the diphosphate one of 10. None of the compounds synthesized proved to possess an appreciable activity on herpes simplex virus (HSV) or human immunodeficiency virus (HIV).
Assuntos
Aciclovir/análogos & derivados , Antivirais/farmacologia , Fosfatos , Animais , Antivirais/química , Chlorocebus aethiops , HIV-1/efeitos dos fármacos , Herpesvirus Humano 1/efeitos dos fármacos , Humanos , Estrutura Molecular , Fosfatos/química , Células Tumorais Cultivadas , Células VeroRESUMO
The 4(5)-aminosubstituted-5(4)-carboxyamido-1H-1,2,3-triazoles constitute a new class of monocyclic compounds as effective inhibitors of XO. In the past to these compounds the structure of 9-unsubstituted-8-azahypoxanthines was wrongly attributed. However some 8-azahypoxanthines obtained via a new annulation reaction have been described in this paper. The inhibitory activity of the title triazoles resulted greater than that shown by the corresponding 8-azahypoxanthines. The inhibitory competitive activity of 4(5)-n-pentyloxyoxalylamino-5(4)-carbamoyl-1H-1,2,3-triazole toward the oxidation of 8-n-pentylhypoxanthine disclosed that only one lipophilic pocket is present within the enzyme.
Assuntos
Triazóis/farmacologia , Xantina Oxidase/antagonistas & inibidores , Estrutura Molecular , Triazóis/químicaRESUMO
Several 2- or 8-n-alkyl-hypoxanthines and a 2,8-di-n-pentyl-hypoxanthine were synthesized and tested as substrates or inhibitors of Xanthine Oxidase (XO). 8-Alkyl derivatives showed a substrate behaviour, whereas 2-alkyl substituted compounds were non-substrates and inhibitors. 2,8-di-n-pentyl-hypoxanthine was ineffective as inhibitor. The comparison between their activity allowed us to conclude that the complexes formed by the enzyme and the cited n-alkylhypoxanthines or 2-n-alkyl-8-azahypoxanthines involve their N(3) and N(9) positions in all the cases. The position of the n-alkyl chain determines the disposition of the molecule inside the complex: 2-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines gave complexes with the same orientation of heterocyclic moieties, opposite that given by 8-n-alkyl-hypoxanthines.
Assuntos
Hipoxantinas/síntese química , Xantina Oxidase/antagonistas & inibidores , Animais , Cromatografia Líquida de Alta Pressão , Hipoxantinas/farmacologia , Cinética , Leite/enzimologia , Conformação Molecular , Plantas/enzimologia , Espectrofotometria Ultravioleta , Relação Estrutura-Atividade , Xantina Oxidase/química , Xantina Oxidase/metabolismoRESUMO
Some N-beta-diethylaminoethylnaphthalimides substituted in the 3 or 3 and 4 positions with alkoxy or butylamino groups or with alkoxy and amino groups (III) have been synthesized by reaction of the appropriate naphthalic anhydride with N,N-diethylethylenediamine. Some compounds (III) were tested to evaluate their anesthetic activity: compounds (III e) and (III f) have been shown to have a greater activity than lidocaine.
Assuntos
Anestésicos Locais/síntese química , Naftalenos/síntese química , Anestésicos Locais/toxicidade , Animais , Fenômenos Químicos , Química , Córnea/efeitos dos fármacos , Etilaminas/síntese química , Etilaminas/farmacologia , Feminino , Masculino , Camundongos , Naftalenos/farmacologia , Coelhos , Tempo de Reação/efeitos dos fármacos , Reflexo/efeitos dos fármacosRESUMO
Synthesis of a pyrido[1,2-a][1,8]naphthyridine (VII) was achieved starting from 7-amino-2,4-dimethyl-1,8-naphthyridine and diethyl ethoxymethylenemalonate. Some derivatives were subjected to pharmacological screening.
Assuntos
Naftiridinas/síntese química , Animais , Hipóxia/prevenção & controle , Camundongos , Naftiridinas/farmacologia , Anafilaxia Cutânea Passiva/efeitos dos fármacos , RatosRESUMO
A series of several 1,2,3-triazole derivatives, by reaction of p-azidophenylacetic and 2-(p-azidophenyl)propionic acids with active methylene compounds, was synthesized. Some of the derivatives obtained were subjected to pharmacological study and among these compounds (II m) showed an analgesic activity 2.5 times greater than phenylbutazone.
Assuntos
Analgésicos/síntese química , Ácidos Carboxílicos/síntese química , Triazóis/síntese química , Animais , Camundongos , RatosRESUMO
The preparation of three series of 1,2,3-triazol derivatives, with a naphthalene, quinoline or pyridine ring in 1 position, is described. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.
Assuntos
Naftalenos/síntese química , Piridinas/síntese química , Quinolinas/síntese química , Triazóis/síntese química , Animais , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Entamoeba histolytica/efeitos dos fármacos , Camundongos , Testes de Sensibilidade Microbiana , Naftalenos/farmacologia , Piridinas/farmacologia , Quinolinas/farmacologia , Ratos , Triazóis/farmacologia , Trichomonas vaginalis/efeitos dos fármacosRESUMO
The reaction of 2-methyl-5-azido-1,8-naphthyridine with active methylene compounds was investigated. Several naphthyridines which possess the 1,2,3-triazole ring as a substituent were obtained. Among these compounds (IV o) showed an analgesic activity twice that of phenylbutazone.
Assuntos
Analgésicos/síntese química , Naftiridinas/síntese química , Triazóis/síntese química , Analgésicos/farmacologia , Animais , Bactérias/efeitos dos fármacos , Fungos/efeitos dos fármacos , Masculino , Camundongos , Naftiridinas/farmacologia , Ratos , Reserpina/antagonistas & inibidores , Triazóis/farmacologiaRESUMO
By treating pyrido (2,3-e)-1,4-diazepinones with alkyl halides, N4-alkylpyrido (2,3-e)-1,4-diazepines were obtained. In addition a number of N1-alkylpyrido (2,3-e)-1,4-diazepines were prepared from alkyltetrahydronaphthyridinones by the Schmidt reaction. Preliminary pharmacological screening of some of these compounds showed no appreciable activity.
Assuntos
Azepinas/síntese química , Piridinas/síntese química , Animais , Azepinas/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Indicadores e Reagentes , Espectroscopia de Ressonância Magnética , Piridinas/farmacologia , Espectrofotometria InfravermelhoRESUMO
The synthesis of a number of 1-alkyl-7-(2-hydroxy-3-alkylaminopropoxy)-1,8-naphthyridin-2-ones is described. The compounds studied were prepared by reaction of 1-alkyl-7-hydroxy-1,8-naphthyridin-2-ones with epichlorohydrin. The substituted epoxy intermediates obtained were allowed to react with amines and gave the desired products. All the compunds prepared were devoid of beta-blocking activity.
Assuntos
Antagonistas Adrenérgicos beta/síntese química , Naftiridinas/síntese química , Antagonistas Adrenérgicos beta/farmacologia , Animais , Anti-Inflamatórios/síntese química , Anticoagulantes/síntese química , Cobaias , Átrios do Coração/efeitos dos fármacos , Indicadores e Reagentes , Naftiridinas/farmacologiaRESUMO
The reaction of 1,8-naphthyridine azides with ethyl acrylate leads to the formation of 2-pyrazolines instead of 1,2,3-triazolines. Some of the compounds obtained have undergone pharmacological and microbiological (antibacterial) testing.
Assuntos
Acrilatos , Azidas , Naftiridinas , Avaliação Pré-Clínica de Medicamentos , Indicadores e Reagentes , Testes de Sensibilidade Microbiana , Pirazóis/síntese químicaRESUMO
The Schmidt reaction on tetrahydro-1,8-naphthyridin-4-ones gave pyrido [2,3-e]-1,4-diazepines and pyrido[2,3-b][1,4]diazepines. The preliminary pharmacological screening of some of these compounds showed no appreciable activity.
Assuntos
Azepinas/síntese química , Antifúngicos , Azepinas/farmacologia , Sistema Cardiovascular/efeitos dos fármacos , Sistema Nervoso Central/efeitos dos fármacos , Fenômenos Químicos , Química , Avaliação Pré-Clínica de Medicamentos , Piridinas/síntese química , Piridinas/farmacologiaRESUMO
The synthesis of N-substituted amino-1,8-naphthyridines is described. Some products were subyected to pharmacological screening and the resulting data are reported.