Il Farmaco; edizione scientifica最新文献

The synthesis of [(1-phenyl-1H-indazol-4-yl)oxy]acetic acid (IV), (1-phenyl-1H-indazol-4-yl)acetic acid (IX) and (1,5,6,7)tetrahydro-1-phenyl-4H-indazol-4-iminooxy)acetic acid (XIII) starting from 1,5,6,7-tetrahydro-1-phenyl-4H-indazol-4-one (I) is described. These compounds showed a good antiinflammatory activity in rats, and an analgesic activity in mice similar or comparable to that of indomethacin.

By acid action on the mixture of homolupinal diethylacetal and arylhydrazines several 3-quinolizidin-1'-yl-5-R-indoles (III a - III e) were prepared. The homolupinal diethylacetal, whose hydrolysis gives rise to the unknown aldehyde, was obtained through the action of lupinylmagnesium chloride on diethylphenylorthoformate. Compounds (III) were subjected to wide pharmacological screening; all of them exhibited calcium blocking, negative cardioinotropic and diuretic activities, while single compounds showed antiinflammatory (III d), anticonvulsant and hypoglycemic (III e) activities.

The antitumor activity of a series of 2-alkyl-3-[2-(1,3,4-thiadiazolyl)]-4-thiazolidinones was tested against the leukemic P 388 tumor system in mice. Only compounds (V-VII) showed significant activity.

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.

The synthesis and antifungal activities of pyrrole analogues of bifonazole are reported. Reduction of 4-nitrobenzophenone to the corresponding alcohol, reaction with phosphorus tribromide of the latter compound and condensation of the bromonitroderivative with imidazole led to 1-[alpha-(4-nitrophenyl)-4'-benzyl]-1H-imidazole. Hydrogenation of the nitro group to amino and reaction with 2,5-dimethoxytetrahydrofuran according to the Clauson-Kaas procedure afforded the pyrrole analogue of bifonazole. This compound and the related chloroderivative were also prepared by a similar pathway starting from 4-(1H-pyrrol-1-yl)benzophenone and its 4'-chloroderivative. Microbiological screening against Candida albicans and Candida spp showed 1-(alpha-[4-(1H-pyrrol-1-yl)phenyl]benzyl)-1H-imidazole to be the most active compound among the tested derivatives.

Some new 2-carbamoylmethylthio- and 2-(omega-dimethylamino-alkyl)thio-3-aryl-7-chloro-4(3H)-quinazolinones have been prepared from 2-thio-3-aryl-7-chloro-4(3H)-quinazolinones as the key intermediate. Five of the synthetic compounds were screened for their CNS activities on mice and found to be either CNS depressants or stimulants.

The synthesis of 1-(2-hydroxyethyl)-3,5-diphenyl-1H-pyrazole (II) and its 4-bromo derivative (III) starting from chalcone epoxide, as well as of a series of esters and N-substituted carbamates derived from (II) and (III), is described. Some of these compounds showed remarkable depressant, antiarrhythmic and analgesic activities in mice and rats. Moreover, the above compounds usually exhibited moderate hypotensive, bradycardic and antiinflammatory activities in rats, infiltration anesthesia and hypoglycemic activity in mice, as well as a weak platelet antiaggregating activity in vitro.

The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported. The N-methylpiperazinyl substituent must be regarded as fundamental to activity. Furthermore the presence of substituents on the para position of the two phenyl rings and the presence of halogen atoms can be considered strengthening factors to microbiological activity. The results obtained are discussed on the basis of structure-activity relationship.