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The synthesis and antifungal activities of new 1,5-diarylpyrrole derivatives are reported. Antimicrobial data in comparison with pyrrolnitrin show that only carboxamide derivatives exhibit satisfactory antifungal activity. By contrast all tested compounds show very poor antibacterial activity. The displacement of NO2 group from para to meta or ortho position of the aryl at C5 of the pyrrole ring affects the antimicrobial activity.

The N,N-disubstituted 4-amino-2H-pyrido[1,2-a]pyrimidin-2-ones (III) and isomer 2-amino-4H-pyrido[1,2-a]pyrimidin-4-ones (IV) were obtained from the reaction of 2-aminopyridine with the N,N-disubstituted ethyl malonamate/phosphorus oxychloride reagent (II), in refluxing 1,2-dichloroethane. 2-[(N-Benzyl, N-ethyl)amino]derivative (IV b) was also prepared in excellent yield by treating 2-chloro-4H-pyrido[1,2-a]pyrimidin-4-one (V) with N-ethylbenzylamine. Finally, hydrogenation (Raney Nickel) of 4-[(N-ethyl,N-phenyl)amino]-2H-pyrido[1,2-a]pyrimidin-2-one (III e) afforded 6,7,8,9-tetrahydroderivative (VI) which in turn was treated with potassium borohydride to give 1,6,7,8,9,9a-hexahydroderivative (VII). Several compounds described in the present paper, along with some other compounds (III) and (IV) previously synthesized by us (1,2), were tested for various pharmacological activities. The antiallergic activity (PCA in the rat), even though found in several compounds examined, turned out to be submaximal in any case, in spite of the high dose administered (500 mg/kg p.o. as a rule). The most active compound (the activity being estimated at 0.42 times that of thiaramide hydrochloride) was the 4-aminoderivative (III e). The 2-aminoderivatives (IV) series, was found to have marked antiinflammatory properties (carrageenin oedema in the rat); nevertheless, this activity was related to toxic symptoms with the exception of compound (IV b), almost asymptomatic at the administered dose (200 mg/kg p.o.). Moreover the 2-aminoderivatives (IV) generally showed weak adrenolitic activity in vitro (rat seminal vesicles), which was estimated to be from 100 to 1000 times less than that of phenoxybenzamine.

As the ultimate result of a long-term search for new bicyclic molecules potentially endowed with antiulcer and/or antisecretory activity, simple urea derivatives of 2-guanidino-4,5,6,7-tetrahydrothiazolo[5,4-c]pyridine [(VIII), Fig. 1; X = 0, R = alkyl], displaying a strong inhibition of stress- and ASA-induced gastric ulcers and of basal gastric secretion, were found. Their potency does compare very favourably with that of cimetidine and ranitidine and approaches that of famotidine. On spontaneously beating guinea pig atria they behaved as inhibitors of the histamine H2-receptor. In contrast with cimetidine and ranitidine but like other recently described inhibitors (famotidine included), the most active compounds (VIII) caused a surmountable antagonism only at low concentrations and an unsurmountable antagonism at higher concentrations. The onset of action was slow, while the inhibitory effect was hardly reversed by washing. The rational development of the research and the synthetic approach, as well as a quantitative assessment of both in vitro and in vivo potencies in comparison with the best known, clinically used drugs, are shown in detail.

This paper reports the synthesis of a new series of acetylenic and allenic derivatives of 2-(1-methylindolyl) methylamine as well as the preliminary results of their study as selective inhibitors of the A and B forms of the mitochondrial monoamine oxidase from bovine brain. The compounds were obtained from 2-(1-methylindole)carboxylic acid which, as its acyl halide, reacts with amines to give the respective amides. The latter compounds were reduced with lithium aluminium hydride to the respective amines (II a-c) and then N-alkylated by reaction with 2-propynyl-, 2-butynyl- or 2,3-butadienyl bromides to the corresponding amines (III a-j).

This paper describes the synthesis and the biological evaluation of some 1,2,3-triazoles which represent structural modifications of two compounds which are effective inhibitors of the prostaglandin synthesis in vitro. These modifications, concerning the elimination of the methylene bridge and/or the ether oxygen from the active molecules, show that every introduced structural changes caused a strong decrease of activity.

A series of tert-aminoalkyl-derivatives of quinoxalin-2-one, aza- and diazaquinoxalin-2-one bearing in position 3 a benzyl group was prepared in order to compare with analogous 3-methyl derivatives as regards analgesic activity. The substitution causes various effects. In compounds (I) and (VI-IX) is found the expected increase in analgesic activity but with contemporaneous rise in toxicity. The compounds (IV) and (V) are of interest due to the presence of a strong separation of DL50 from DE50.

The trypanocidal activity of a new class of arsenical compounds, the spiroarsorans, was investigated against Trypanosoma brucei brucei. The most active compound was found to be effective at a dose of 30 mg.kg-1 and had low toxicity.

The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate dehydrogenase and aspartate aminotransferase), the electron transfer chain (cytochrome oxidase) and NAD+/NADH exchanges (total NADH cytochrome c reductase) was evaluated. Some glycolytic metabolites and Krebs' cycle intermediates were modified by acute hypoxia, while free amino acids and energy mediators remained practically unchanged. The pharmacological treatment maintained the glucose and succinate muscular concentrations within the normal range, during hypoxia. The behaviour of muscular metabolites during hypoxia and/or post-hypoxic recovery is an age-related event. In fact, only in young-adult animals did the altered values return to normal in post-hypoxic recovery. In the present experimental conditions, only minor changes were observed as far as muscular enzyme activities are concerned. In any case, some enzyme activities tested showed different Vmax in young-adult dogs in comparison with mature ones.

The new 3-azinomethyl-rifamycin, SPA-S-565, was shown to exert an effective antibacterial activity in vitro comparable to that of rifampicin. In fact, the antibacterial activity of SPA-S-565 against numerous Gram-positive cocci belonging to Staphylococcus and Streptococcus species as well as against 20 strains of Mycobacterium tuberculosis, was similar to that of rifampicin. In Swiss albino mice intraperitoneally infected with Staphylococcus aureus Oxford strain or Streptococcus pyogenes, the protective activity of SPA-S-565 and rifampicin was quite remarkable, and no significant difference was noted between the two antibiotics. In M. tuberculosis-infected mice treated with the antibacterial agents every seven days, the protection exerted by SPA-S-565 was significantly greater than that exerted by rifampicin.

Some N-acyl- and N-carbamoylderivatives of 3-aroylanilines were prepared and tested for phytoiatric antimycotic activity. The substances, all unknown, were subjected to in vitro and in vivo tests (in preventive phase). The compounds studied proved to have interesting activity.