Novel adenosine receptor ligands: 1,3-disubstituted[1]benzopyrano[2,3-c]pyrazol-4-ones. Synthesis and structure-activity relationships.

A series of 1,3-disubstituted[1]benzopyrano[2,3-c]pyrazol-4-ones were synthesized and tested in vitro as A1 and A2 adenosine receptor ligands. The binding results and a molecular modelling study indicated that the presence of a proton donor group in the N6-H region of adenosine and the 7-NH region of xanthine, respectively and occupancy of the A2 lipophilic area by a moiety endowed with an electrostatic effect are essential for receptor affinity and A2-selectivity.

[Thrombosis of the superior sagittal sinus and ulcerative colitis. A case report].

We describe a rare case of superior sagittal sinus thrombosis in a young man (26 years) with undiagnosed ulcerative colitis. The patient was hospitalized with headache and paresis of the right arm and leg. he had had rectal bleeding and diarrhea for the previous 4 weeks.

Tricyclic heteroaromatic systems. Synthesis and benzodiazepine binding activity of 1-substituted-3-methyl- and 3-phenylpyrazolo[4,5-c]quinolin-4-ones.

The synthesis and the benzodiazepine binding activity of some 3-methyl- and 3-phenylpyrazolo[4,5-c]quinolin-4-ones bearing a heterocyclic or a substituent which is different from an aryl moiety at position-1 are reported. Molecular modelling is used to correlate the binding affinity to the chemical features and to justify the reduced receptor affinities of the reported compounds with respect to that of CGS 8216 which is taken as the lead compound.

Tricyclic heteroaromatic systems. Synthesis of 1,3 and 1,2 disubstituted [1]benzopyrano[4,3-b]pyrrol-4-ones and structure-activity relationships as benzodiazepine receptor ligands.

The synthesis of some 1,3- and 1,2- disubstituted [1]benzopyrano-pyrrol-4-ones is reported as well as their benzodiazepine receptor affinity, as measured by the ability to displace [3H]flunitrazepam from its specific central binding. The structure-activity relationships on the whole series of disubstituted [1]benzopyrano-pyrrol-4-ones show the importance of the presence of the 1-aryl substituent and the size limitation of the 3-substituent. The size of the latter seems also to be important for the "in vitro" efficacy.

Tricyclic heteroaromatic systems: [1]benzopyrano-pyrazol-4-ones as benzodiazepine receptor ligands.

The synthesis of a series of 8-substituted 1,4-dihydro-1-aryl-3-methyl-[1]benzopyrano[3,4-d]pyrazol-4-ones (series 7) 2,4-dihydro-2-aryl-3-methyl[1]benzopyrano[4,3-c]pyrazol-4-ones (series 8) is reported. Compounds of series 7 and 8 were tested for their ability to displace [3H]flunitrazepam from bovine brain membranes and for their in vitro biological activity. The results allowed some conclusions to be drawn about the structural requirements of the benzodiazepine recognition site within this class of unusual ligands.

Lactic acid enantiomers: separation by thin-layer chromatography on silica gel plates impregnated with Cu2+.

A simple and fast method for the separation of D- and L-lactic acid enantiomers by thin-layer chromatographic silica gel precoated plates impregnated with Cu(II) is proposed. The two lactic acid enantiomers, dissolved in acetone, are deposed on these plates. D- and L-lactic acids form complexes with Cu(II), with different Rf values, suitable for radiochemical measurements.

Tricyclic heteroaromatic systems. [1]benzopyranopyrrol-4-ones and [1]benzopyrano-1,2,3-triazol-4-ones as benzodiazepine receptor ligands. Synthesis and structure-activity relationships.

The synthesis, ability to displace [3H]flunitrazepam binding from bovine brain membranes, and GABA ratio of some [1]benzopyranopyrroles 1a-i and [1]benzopyrano-1,2,3-triazoles 2a,b are reported. The GABA ratios of some previously synthesized pyrazoloquinolines A and [1]benzopyranopyrazoles C are also presented in order to draw some structure-activity relationships among our benzodiazepine receptor ligands. 1,3-Diarylpyrrole derivatives 1a-h show similar affinity and efficacy to that of diazepam, while the 1-aryltriazoles 2a,b have no receptor affinity.

Abnormalities of short-latency somatosensory evoked potentials in parkinsonian patients.

Twenty-two patients (16 affected by parkinsonian syndromes, 6 by other neurological diseases) and 12 age-matched controls were examined. Short-latency somatosensory evoked potentials were recorded from 30 scalp electrodes in the 45-52 msec following separate left and right median nerve stimulation at the wrist. Bit-colour maps were generated on a 4096 pixel matrix via quadratic interpolation.

Dipyrazolo[5,4-b:3',4'-d]pyridines. Synthesis, inhibition of benzodiazepine receptor binding and structure-activity relationships.

Some 2,6,8-trisubstituted dipyrazolo[5,4-b:3',4'-d]pyridin-3-ones related to the CGS series were synthesized and tested for their ability to displace [3H]flunitrazepam binding from bovine brain membranes. However the affinity for the benzodiazepine receptor of the tested compounds was lower than that of the CGS series, although it was comparable to that of chlordiazepoxide. It follows that some structure-activity relationships on the tested compounds can be drawn.

Synthesis of 1,5-diaryl-3-methyl-1H-pyrazolo[4,5-c]isoquinolines and studies of binding to specific peripheral benzodiazepine binding sites.

Some 1,5-diaryl-3-methyl-1H-pyrazolo[4,5-c]isoquinolines were synthesized and tested for their ability to displace [3H]clonazepam or [3H]Ro 5-4864 from their specific binding on the central and peripheral benzodiazepine receptors. None of the tested compounds showed any activity as central binding inhibitors, while most of them were specific as peripheral binding inhibitors, although they were not very potent.

Short latency somatosensory evoked responses to median nerve stimulation in healthy humans: electric and magnetic recordings.

Somatosensory Evoked Potentials (SEPs) and Somatosensory Evoked magnetic Fields (SEFs) to median nerve stimulation at wrist were recorded in 5 healthy subjects and the components between 15 and 30 ms after the stimulus were evaluated on the hemiscalp contralateral to the stimulated wrist. SEPs were measured by means of a 32-channel recorder and compared with SEFs obtained via multiple measurements with a 4-channel sensor. Equivalent dipole localization was carried out for the magnetic components peaking at about 15, 20 and 24 ms.

Tricyclic heteroaromatic systems: synthesis, [3H]flunitrazepam brain membrane binding inhibition, and structure-activity relationships of 2,3-dihydro-2-aryl-4-R-[1]benzopyrano[4,3-c]pyrazole-3-ones.

We report the synthesis and binding activity to the central benzodiazepine receptors of some 2,3-dihydro-2-aryl-4-R-[1]benzopyrano[4,3-c]pyrazole-3-ones, which are isosteres of the CGS series. Although the compounds of the CGS series are potent ligands of the benzodiazepine receptors, none of the isosteres tested showed any significant inhibiting potency. This may be due to the change in electronic properties brought about by the replacement of the NH of the CGS series with an oxygen atom.

Incidence of stroke in young adults in Florence, Italy.

A population-based study specifically addressing stroke in young adults (aged 15-44 years) was conducted in Florence, Italy, from 1983 to 1985. We identified 47 cases of first stroke by means of a daily check of the medical facilities of the city and nearby towns and a review of death certificates. Patients were assessed by a neurologist shortly after the onset of the stroke, and computed tomography or autopsy was performed in 96%.

1,3-Diarylpyrazolo[4,5-c]- and -[5,4-c]quinolin-4-ones. 4. Synthesis and specific inhibition of benzodiazepine receptor binding.

A series of 1,3-diarylpyrazolo[4,5-c]- and -[5,4-c]quinolin-4-ones were prepared and tested for their ability to displace [3H]flunitrazepam from bovine brain membranes. While the 1,3-diarylpyrazolo[4,5-c]quinoline derivatives showed affinity for the receptor site, their [5,4-c] isomers were devoid of binding activity.

Synthesis and binding study on pyrazolo[4,5-c] [1,8]naphthyridines.

Following our previous reports on pyrazolo[4,5-c]quinoline derivatives some isosteric pyrazolo[4,5-c] [1,8]naphthyridines were synthesized and tested for their ability to displace [3H]flunitrazepam from rat brain membranes. The lack of activity of the synthesized compounds and structure-activity relationships for the whole series are discussed.

Pyrazolo[4,5-c]quinolines. 3. Synthesis, receptor binding, and 13C NMR study.

Some 1-aryl-3-methylpyrazolo[4,5-c]quinolin-4-ones, were prepared and tested for their ability to displace specific [3H]flunitrazepam binding from bovine brain membranes. The 1-meta-aryl derivatives were the compounds that bound with the highest affinity within this class. Our 13C NMR study suggested a correlation between the binding affinity and the chemical shift value of a carbon atom of the tricyclic system.

Pyrrolnitrin analogues. XII. Synthesis and biological activity of some pyrazole carboxylic acids.

Some 1,5-diaryl-, 1-aryl-5-(2-nitrobenzyl)-3-methylpyraloze-4-carboxylic acids and some of their 4-morpholino- and 4-N-methylpiperazino amides are prepared and tested as antibacterial agents. None of the tested compounds shows any noteworthy antimicrobial activity. The results are discussed and compared with the previously published results for other similarly structured compounds.

Pyrazolo[4,5-c]quinolines. 2. Synthesis and specific inhibition of benzodiazepine receptor binding.

A series of 1-aryl-3,5-dimethyl-4,5-dihydro-1H-pyrazolo[4,5-c]quinolin-4-ones (2a-e) and 1-aryl-3-methyl-1H-pyrazolo[4,5-c]quinolines (3-7a-e) bearing different substituents at position 4 were prepared and tested for their ability to displace specific [3H]flunitrazepam binding from bovine brain membranes. The 5-N-methyl derivatives 2a-c,e were the compounds that bound with the highest affinity within this class. The replacement of the carbonyl group with other substituents and the resulting aromatization of the pyridine moiety greatly decreased the binding affinity.

Synthesis and binding studies of 1-arylpyrazolo[4,5-c]- and 2-arylpyrazolo[4,3-c]quinolin-4-ones. I.

The syntheses of some 2-aryl-3-methyl-4,5-dihydro-2H-pyrazolo [4,3-c] quinolin-4-ones and 1-aryl-3-methyl-4,5-dihydro-1H-pyrazolo-[4,5-c] quinolin-4-ones are reported. Some of the latter have shown a high activity in displacing specific [3H]-flunitrazepam binding from bovine brain membranes.

Pyrrolnitrin analogues. X. Synthesis and biological activity of 1-chlorophenyl-3- or 5-nitrophenyl-pyrazole-4-carboxylic acids.

The synthesis and the in vitro antimicrobial activity of all the possible 1-chlorophenyl-3-nitrophenyl-5-methylpyrazole-4-carboxylic acids and 1-chlorophenyl-3-methyl-5-nitrophenylpyrazole-4-carboxylic acids are reported. Some acids showed an interesting activity against some strains of gram-positive bacteria. The results are discussed and compared with those of other related compounds.

Synthesis and biological activity of some 3-(pyrazol-1'-yl)indazole derivatives.

The synthesis of some 3-(pyrazol-1'-yl)indazole derivatives is reported. The synthesized compounds were subjected to in vitro antimicrobial screenings. Only two of the tested compounds showed a mild activity at high concentrations.

Pyrrolnitrin analogues. IX. Synthesis and biological activity of 1-tolyl-3-nitrophenyl-5-methylpyrazole-4-carboxylic acids and 1-tolyl-3-methyl-5-nitrophenylpyrazole-4-carboxylic acids.

The syntheses of all the possible 1-tolyl-3-nitrophenyl-5-methylpyrazole-4-carboxylic acids, 1-tolyl-3-methyl-5-nitrophenylprazole-4-carboxylic acids and of the corresponding carboxylates are reported. Several 1,3- and 1,5-diarylpyrazole derivatives were subjected to in vitro antibacterial screenings. Some acids showed activity against some strains of gram-positive bacteria.

2-Phenylpyrazolo[1,5-a]pyrimidin-7-ones. A new class of nonsteroidal antiinflammatory drugs devoid of ulcerogenic activity.

Syntheses of some pyrazolo[1,5-a]pyrimidines were performed in order to study the relationship between structural modifications on the parent 4,7-dihydro-2-phenylpyrazolo[1,5-a]pyrimidin-7-one (1) and their antiinflammatory properties. The modifications carried out were introduction and functionalization of a longer side chain at the 4-position, substitution of the hydrogen atom at the 3-position, and replacement of the phenyl group with a 4-methylphenyl, methyl, or hydrogen substituent. 4-Ethyl-4,7-dihydro-2-phenylpyrazolo [1,5-a]pyrimidin-7-one (3) showed the highest activity and a better therapeutic index than phenylbutazone and indomethacin, used as reference drugs.