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Bischler-Napieralski intramolecular cyclization of N-(2-aroylaminophenyl)-N-methyl-1H-pyrrol-1-amines and reaction of arylaldehydes on N-(2-aminophenyl)-N-methyl-1H-pyrrol-1-amine furnished 11-aryl-5-methyl-5H-pyrrolo[1,2-b][1,2,5]benzotriazepines and 11-aryl-10,11-dihydro-5-methyl-5H-pyrrolo[1,2-b][1,2,5]benzotriazepin es respectively. The latter reaction required in some cases the use of p-toluenesulphonic acid as a catalyst. The new tricyclic derivatives described were tested for pharmacological evaluation of their psychotropic activity.

The synthesis of derivatives of 4H,6H-pyrrolo[1,2-a][4,1]-benzoxazepine is described. These compounds were tested for activity on type (I) and (II) benzodiazepine receptors by several screening tests on mice.

Some p-methylbenzolpyrrole acrylic acids and related compounds were synthesized. The new pyrrole derivatives have structural features in common with trichostatin A, an antifungal antibiotic. The above acids and derivatives were tested against Candida albicans and Candida sp in comparison with miconazole, pyrrolnitrin and amphotericin B and showed very weak antifungal activities. Occasionally some activity was found against a few strains of Candida albicans and against Candida pseudotropicalis.

A new analog of nalidixic acid, 1-ethyl-1,4-dihydro-4-oxo--7-(1-pyrryl)quinoline-3-carboxylic acid, is described. When tested against gram-positive and gram-negative bacteria this compound showed many significant activities and was more active than nalidixic, piromidic and pipemidic acids. On the contrary its 6-chloro- and 6-methylderivatives lack antimicrobial activities. All new compounds here described were synthesized by standard procedures via Gould-Jacobs reaction.

The synthesis and antimicrobial activities against Gram-positive and Gram-negative bacteria of some 1-substituted quinolones related to pirfloxacin are reported. Compounds with a benzyl moiety at 1-position were generally found to be less active than the analogues bearing an unsaturated alkyl chain at the same position. Introduction of fluorine or chlorine in the benzyl moiety did not increase the antibacterial activity. All derivatives here reported were inferior to pirfloxacin as regards antibacterial power, but always superior in comparison with nalidixic acid and pipemidic acid against Gram-positive microorganisms.

The synthesis of 5H-imidazo [2,1-c] [1,4] benzodiazepine derivatives is described. Hydroxymethylation of 1-(2-nitrobenzyl)imidazoles by reaction with formaldehyde in a sealed tube and subsequent oxidation of hydroxymethylimidazoles with activated manganese dioxide afforded 1-(2-nitrobenzyl)imidazole-2-carboxaldehydes. The latter compounds were treated with iron(II) sulphate to yield directly the expected tricyclic imidazobenzodiazepines by intramolecular cyclization of the intermediates aminoaldehydes. The tricyclic derivatives were subjected to pharmacological screening to evaluate the effects on the behavior of the animals and the interaction with some biogenic amines. Some of the tested compounds were comparable to chlordiazepoxide in sedative and muscle-relaxant activities. None of them showed antiserotonin, anticholinergic or adrenolytic activities.

Some hydrazides of pyrrol-1-ylbenzoic and pyrrol-1-ylphenylacetic acids were prepared, and their effect on copper-dependent amine oxidases (Cu-AOs) and FAD monoamine oxidases (MAOs) activities was tested. The compounds were not substrates for Cu-AO enzymes but acted as noncompetitive inhibitors. Hydrazides of pyrrol-1-ylphenylacetic acids were highly specific for plasma amine oxidase (Ki = 0.5-1 microM). In contrast, all the hydrazides were weak inhibitors of MAO activity. Incubation with the hydrazide derivatives led to irreversible inactivation of Cu-AOs. Therefore, the inhibition implied two distinct steps. The first one consisted of the rapid formation of the enzyme-inhibitor complex and was reversed by dialysis. In the second step, the complex was irreversibly transformed, probably by the formation of a Schiff base between the hydrazide and the prosthetic carbonyl group of the enzyme.

Diethyl 3-carbazolylaminomethylenemalonate undergoes Lappin cyclization giving 2-carbethoxy-1-oxo-1,4-dihydro-7H-pyrido[2,3-c]carbazole. Formation of an angular pyridocarbazole derivative is consistent with the Markwald rule. The synthesis of 4-ethyl derivatives of the above pyridocarbazole and its 8,9,10,11-tetrahydro derivative is also reported as a goal to potential indoloquinolone antitumoral agents.

The synthesis of 1-aryl-5-(1-pyrryl)pyrazoles bearing at position 4 an acetic or alpha-propionic chain is described. The new compounds can be structurally related to lonazolac and its analogues with analgesic-antiinflammatory activities. When tested pharmacologically in comparison with tolmetin and indomethacin none of the above derivatives showed any appreciable activity.

The synthesis of pyrrole analogues of the analgesic drug lefetamine is reported. These derivatives bear the 1-phenyl-2-(1H-pyrrol-1-yl)ethylamino moiety. Compounds were evaluated for analgesic activities in mice by the hot plate and Randall-Selitto tests. Antiinflammatory activity was tested by the carrageenan-induced rat paw edema method. General neuropsychopharmacological effects were also screened. The most interesting compound, N,N-dimethyl-1-phenyl-2-(1H-pyrrol-1-yl)ethylamine, showed an analgesic effect comparable to that of lefetamine, but devoid of the neurotoxicity of this drug.

A new route to pirfloxacin, a fluorinated pyrrylquinolone with high broad-spectrum antibacterial activities, is described starting from 7-amino-1-ethyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid and 2,5-dimethoxytetrahydrofuran. When the reaction with the latter compound was carried out using the ethyl ester of the above acid the related pyrryl ester formed, which on alkaline hydrolysis gave pirfloxacin. The synthesis and antibacterial activities of the 1-allyl analogue of pirfloxacin and of 7-[2-(1-pyrrolidinomethyl)-1-pyrryl]-1-ethyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid and its 6-fluoroderivative are also reported.