Synthesis and in vitro selective anti-Helicobacter pylori activity of pyrazoline derivatives.

In order to develop new anti-Helicobacter pylori agents, a series of N1-substituted 3,5-diphenyl pyrazolines P1-P13 was prepared and evaluated for their antibacterial activity. All synthesized compounds showed little or no activity against different species of Gram-positive and Gram-negative bacteria of clinical relevance and against various strains of pathogenic fungi. The same derivatives exhibited a significant degree of activity against a range of H. pylori strains, including those resistant to the reference compound metronidazole. Among the prepared compounds those with an N1-acetyl group and a 4-methoxy substituent in the 5-phenyl ring showed the best activity against H. pylori metronidazole resistant strains in the 1-4 microg/mL MIC range.

Synthesis and preliminary biological evaluation of 4,6-disubstituted 3-cyanopyridin-2(1H)-ones, a new class of calcium entry blockers.

The preparation of 3-cyano-4,6-diaryl-pyridin-2(1H)-ones 4a-h, calcium entry blockers related to diltiazem, is described starting from 1,3-diaryl-2-propen-1-ones 5. On preliminary pharmacological tests all compounds are active and some of them show calcium antagonistic activity superior or comparable to diltiazem.

Inhibitory effect of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives on activity of amine oxidases.

A new series of 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives was synthesized to ascertain the contribution of substituted phenyl rings present on the 4,5-dihydro-(1H)-pyrazole nucleus to the monoamine oxidases inhibition and bovine serum amine oxidase inhibition. All compounds were tested on bovine brain mitochondria preparation containing flavin-monoamine oxidases and on purified bovine serum amine oxidases, taken as a model of trihydroxyphenylalanine quinone-copper-containing amine oxidases. The 1,3,5-triphenyl-4,5-dihydro-(1H)-pyrazole derivatives showed a good inhibitory activity and belonged to the third generation of monoamine oxidase inhibitors and bovine serum amine oxidase inhibitors which have the advantage of acting through a reversible mode. Furthermore, their activity showed a good degree of selectivity towards the bovine serum amine oxidase inhibition dependent on the substituents present on the phenyl ring at position 5 of the 4,5-dihydro-(1H)-pyrazole.

Beta-adrenoreceptor blocking heterocyclic oximes and ethers.

This paper reports synthesis and pharmacological properties of thienyl, pyrrol, indolyl and benzofuryl-O-(3-alkylamine-2-hydroxypropyl)oximes and some 3-(3-alkylamine-2-hydroxypropyl)alkyloxy indoles aiming to study the influence of five membered and condensed heterocyclic substituents on the beta-adrenoreceptor inhibiting potency. All heterocyclic derivatives synthesized (1-17) were less active than the reference propranolol on the rat heart, while showed a comparable potency on the guinea pig trachea, exhibiting a significant beta 2-selectivity. The low beta-blocking potency of the five membered derivatives seemed to confirm the negative influence of the polarization of the oximic carbon in the binding with non polar region of the beta-adrenoreceptor. Another important interaction could take place with the enzyme adenyl-cyclase which is responsible of the signal of transduction. It could be hypothesized that the heteroatom of the heterocyclic nucleus acted as an electron-donor group and engaged a coordinative bond with magnesium atom present on the adenylcyclase system, responsible of the agonist activity. The pharmacological in vivo experiments and the binding results were in accordance with the in vitro data.

Synthesis and beta-adrenoreceptor blocking activity of [[3-(alkylamine)-2-hydroxypropyl]oximino]pyridines and O[3-(alkylamine)-2-hydroxypropyl]methylpyridine ketone oximes derivatives.

[[3-(alkylamine)-2-hydroxypropyl]-2-oximino]pyridines and O-[3-(alkylamine)-2-hydroxypropyl]methylpyridine ketone oximes 5a-o were synthesized by a solid-liquid phase-transfer reaction, and their beta-adrenoreceptor blocking activity was evaluated in vitro and in vivo. The replacement of the aryl linked to the oximic carbon of the (methylenaminoxy)methyl moiety with the bioisoster pyridine ring produced a decrease of the beta-adrenergic blocking activity. The polarization of the oximic group, derived from the electron-withdrawing action of the nitrogen atom, is more evident for the 2-oxyminopyridine derivative 5d. But also conformational parameters may play an important role in the variation of activity of the compounds 5d, 5l and 5n. The replacement of the hydrogen linked to the oximic carbon with a methyl group increased the activity of the compounds 5a, 5i, 5m and 5o. The methyl could allow a delocalization of the partial positive charge present on the oximic carbon, but also its lipophilicity contributed to the increment of binding to the receptor site. None of the compounds showed high beta 1 or beta 2 selectivity in vitro. The (R) and (S) isomers of the compound 5a were synthesized and obtained with enantiomeric ratio 7:3 and 6:4, respectively. The binding tests and the pharmacological in vivo results confirmed the in vitro data.

Study on selective quantitative determination of barium by sulphonazo III in complex matrices.

Selective quantitative determination of barium by commercially available Sulphonazo III was studied in complex matrices. The application of two more promising methods was tried, but interferences derived from cations and anions present in natural waters and waste waters made them unuseful.

[A substance with antibacterial and antifungal activity. IV. Synthesis and microbiological activity of new 1,5-diarylpyrrole derivatives]. / Ricerche su sostanze ad attività antibatterica ed antifungina. Nota IV--Sintesi ed attività microbiologica di nuovi derivati 1,5-diarilpirrolici.

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.

[A substance with antibacterial and antifungal activity. V. Synthesis and microbiological activity of new derivatives of 1,5-diarylpyrrole]. / Ricerche su sostanze ad attività antibatterica ed antifungina. Nota V--Sintesi ed attività microbiologica di nuovi derivati 1,5-diarilpirrolici.

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.

Research on antibacterial and antifungal agents. III. Synthesis and antimicrobial activity of 2-methyl-5-aryl-3-furoic acids and 2-methyl-3-imidazolylmethyl-5-aryl furans.

The synthesis and microbiological activities of 2-methyl-5-aryl-3-furoic acids and 2-methyl-3-imidazolyl-methyl-5-aryl-3-furans are reported. Antimicrobial data in comparison with pyrrolnitrin showed an interesting antifungal activity but a very poor antibacterial activity. The presence of an imidazole nucleus does not increase antifungal activity. The introduction of a substituent in the para position of the aryl at a C5 of the furan ring affects antifungal activity.

[Substances inhibiting amine oxidases. III. Synthesis and amine oxidase inhibition of imidazoquinoline derivatives]. / Ricerche su sostanze inibitrici delle aminossidasi. Nota III. Sintesi ed attività inibitrice sulle aminossidasi di derivati delle imidazochinoline.

The activity of copper and FAD dependent amine oxidases was tested with some derivatives of 3H-imidazo[4,5-h]quinoline and its isomers 3H-imidazo[4,5-f]quinoline, the chemistry of which is described in the literature (1), and Ki calculated. The methyl derivative of 3H-imidazo[4,5-f]quinoline was found to activate the copper bovine serum enzyme, but inhibits the FAD mitochondrial enzyme.

Pyrrolnitrin analogues. XI--Synthesis and microbiological activity of new 1,4- and 1,5-diarylpyrroles.

The synthesis and microbiological activities of new 1,4- and 1,5-diarylpyrroles is reported. Antimicrobial data in comparison with fungal antibiotic pyrrolnitrin confirm an interesting antimicotic activity of 1,4-diarylpyrroles. On the contrary 1,5-diarylpyrroles show antibacterial activity and an unexpected antimicotic activity. The position of the 4-nitrophenyl group at C4 or C5 of the pyrrole ring influences antibacterial activity.

[Substances inhibiting monoamine oxidase. II. Inhibition of bovine plasma amine oxidase by N-cyclopropyltryptamines]. / Ricerche su sostanze inibitrici delle monoaminossidasi. Nota II. Inibizione delle aminossidasi da plasma bovino da parte di N-ciclopropiltriptamine.

In this paper, we report the inhibition constants obtained with N-cyclopropyl-5,6-dimethoxytryptamine and with N-cyclopropyl-6,7-dimethoxytryptamine on the activity of beef plasma amineoxidase. The inhibition constants are respectively: 0.3 x 10(-3) M and 0.65 x 10(-3) M. A dixon graph of the enzymic oxidation of benzylamine indicates a non-competitive inhibition of the enzyme by these dimethoxytryptamines.

[Monoamine oxidase inhibitors. I. Synthesis of N-cyclopropyltryptamines]. / Richerche su sostanze inibitrici delle monoaminossidasi. Nota I. Sintesi di N-ciclopropiltriptamine.

The synthesis of two new N-cyclopropyltryptamines is described. By treating 5,6-dimethoxyindole with oxalyl chloride and N-benzylcyclopropylamine, N-benzyl-N-cyclopropyl-5,6-dimethoxyindole-3-glyoxalamide is obtained. The reduction of this compound by LiAlH4, gives N-benzyl-N-cyclopropyl-5,6-dimethoxytryptamine, which is hydrogenated to N-cyclopropyl-5,6-dimethoxytryptamine. Similarly N-cyclopropyl-6,7-dimethoxytryptamine is prepared. Preliminary results indicate a different specificity of the inhibitors used on mitochondrial and bovine plasma enzyme (monoamine oxidase) attributable to the position of the methoxy groups.

[Studies on substances with antiblastic activity. IX. Anthramycin and analogs. IX. Synthesis of 7-methoxy-8-hydroxy-10,11-dihydro-5H-pyrrolo[2,1-c] [1,4] benzodiazepine and other compounds related to oxotomaymycin]. / Richerche su sotanze ad attivtià antiblastica. Nota LX - Antramicina e composti analoghi. Parte IX: Sintesi della 7-metossi-8-idrossi-10,11-diidro-5H-pirrolo[2,4-c] [1,4]benzodiazepina e di altri composti correlati con la oxotomaimicina.

The synthesis of some pyrrolobenzodiazepine derivatives related to oxotomaymycin, an antibiotic recovered together with tomaymycin from fermentation broths of Streptomyces achromogenes var. tomaymycetics, is described. Reaction between 2-nitro-4-benzyloxy-5-methoxybenzylbromide and pyrrole-2-carboxyaldehyde afforded 1-(2-nitro-4-benzyloxy-5-methoxybenzyl)pyrrole-2-carboxyaldehyde. Catalytic reduction of this compound with hydrogen in the presence of Pd/C gave 10,11-dihydro-8-hydroxy-7-methoxy-5H-pyrrolo[2.1-c] [1,4]benzodiazepine. Amides obtained from condensation between 2-nitro-4-benzyloxy-5-methoxybenzoic acid chloride and proline or hydroxyproline were reduced catalytically to 2,3-dihydro-8-hydroxy-7-methoxy-1H-pyrrolo [2,1-c] [1,4]benzodiazepine-5,11 (10H, 11aH)-dione and its 2-hydroxyderivative respectively. The synthesis of 10,11-dihydro-8-hydroxy-9-methoxy-5-pyrrolo [2,1-c] [1,4]benzodiazepine is also reported.