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L Cecchi

Publications and source records attributed to L Cecchi.

At least 37 records · Page 2Linked to original sources
PubMed1996

Structure-activity relationship studies of novel pyrazolo[1,5-c][1,3]benzoxazines: synthesis and benzodiazepine receptor affinity.

Some 2-arylpyrazolo[1,5-c][1,3]benzoxazin-5-ones 1 and 5- oxopyrazolo[1,5-c][1,3]benzoxazin-2-carboxylates 2 were prepared and biologically evaluated for their binding at benzodiazepine receptor (BZR) in rat cortical membranes. Structure-activity relationship studies suggest that, although proton donor d and proton acceptor a1 are both optional pharmacophoric descriptors, at least one of them must be present for good BZR affinity. When the proton donor d is not present, the heteroatom acceptor a1 is necessary either in the tricyclic core or in the appended substituent at the C-2 to obtain sub-micromolar BZR affinity.

Animals↗
PubMed1995

Synthesis of some 2-aryl-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones as tools to define the essential pharmacophoric descriptors of a benzodiazepine receptor ligand.

The synthesis and benzodiazepine receptor (BZR) affinity of some 1,2,4-triazolo[1,5-c][1,3]benzoxazin-5-ones, 2-22, are reported. Compounds 2-22 are devoid of the proton donor group, which according to a BZR schematic model was one of the pharmacophoric descriptors for receptor-ligand interaction. The binding data show that 2-(2-fluorophenyl)-9-chloro-1,2,4-triazolo[1,5-c][1,3]benzoxazin-5 -one (12) and some other compounds display nanomolar BZR affinity, indicating that the hydrogen donor group is not essential for the anchoring of 6,6,5-tricyclic systems to the BZR but only affects the potency of a ligand.

Animals↗
PubMed1995

Tricyclic heteroaromatic systems. Synthesis and A1 and A2a adenosine binding activities of some 1-aryl-1,4-dihydro-3-methyl[1]benzopyrano[2,3-c] pyrazol-4-ones, 1-aryl-4,9-dihydro-3-methyl-1H-pyrazolo[3,4-b]quinolin-4- ones, and 1-aryl-1H-imidazo[4,5-b]quinoxalines.

The syntheses and A1 and A2a adenosine binding activities of some new 1-aryl-1,4-dihydro-3-methyl[1]benzopyrano[2,3-c]pyrazol-4-ones, 1-aryl-4,9-dihydro-3-methyl-1H-pyrazolo[3,4-b]-quinolin-4-ones, and 1-aryl-1H-imidazo[4,5-b]quinoxalines are reported. Some compounds show A1 adenosine receptor affinity and selectivity. Structure-activity relationships on these new classes of adenosine receptor ligands are defined.

Animals↗
PubMed1994

Structure-activity relationships of 1,2,4-triazolo[1,5-a] quinoxalines and their 1-deaza analogues imidazo[1,2-a]quinoxalines at the benzodiazepine receptor.

The synthesis, BZR binding activity, and GABA ratio of some 1,2,4-triazolo[1,5-a]quinoxalines and imidazo[1,2-a]quinoxalines are reported. Both series of compounds displayed similar affinities while their efficacies were different. The structure-activity relationships have provided the opportunity to localize on the BZR accessory areas which are able to enhance the affinity and evaluate the importance of the presence or absence of a proton acceptor atom to determine different trends of efficacy.

Animals↗
PubMed1994

Statistical analysis of topographic maps of short-latency somatosensory evoked potentials in normal and parkinsonian subjects.

This work had the following objectives: i) to integrate temporal analysis (N30 peak) with power-spectrum topographic mapping of short-latency somatosensory evoked potentials (SEP's) recorded in parkinsonian and normal control subjects; and ii) to analyze with a new statistical approach the between-group topographical differences in both the time and frequency domains. The principal aim was to better determine the topography of the scalp frontal areas where the amplitude of the N30 wave was previously found to be significantly reduced in parkinsonians. The statistical procedure was based on the combined use of descriptive data analysis (DDA) and multivariate analysis. In the context of DDA, an improved version of significance probability mapping (SPM) was used by which it is possible to evaluate homo- and nonhomoscedastic data with parametric tests. The statistical evaluation of between-group differences was performed with the multivariate Hotelling's T2 test and the associated post hoc test. With this statistical procedure, it was possible to determine that the between-group statistical differences in both the temporal and power spectrum distributions were localized only in midline and contiguous contralateral frontal areas of the scalp.

Brain Mapping↗
PubMed1994

Fosinopril in the treatment of hypertension: effects on 24h ambulatory blood pressure and on blood pressure response to exercise.

This study evaluated the effects of medium-term once daily administration of fosinopril (20 mg) on BP profile and on BP response to exercise in patients with mild to moderate hypertension. Twenty patients (14 males and 6 females; 25-57 years of age), after a six week drug wash-out phase, underwent 24h ambulatory BP monitoring (ABPM) (Spacelabs 90207) and, the day after, maximal bicycle exercise testing. Patients then received a once daily treatment with fosinopril and ABPM and exercise testing were repeated 45-60 days later. Fosinopril decreased average 24h SBP and DBP (-13.5 mmHg and -9.7 mmHg, respectively, P < 0.002); a significant BP reduction was observed both in day and in nighttime, without alteration in diurnal BP profile. The antihypertensive effect was still evident 24h after dosing. Trough to peak ratio was 0.58 +/- 0.16. Fosinopril induced a reduction of SBP and DBP during exercise testing (-20 and -11 mmHg at baseline; -17 and -8 mmHg at peak exercise; -24 and -14 mmHg at the sixth minute of recovery; P < 0.002), with a slight prolongation of exercise time (+46 seconds, P = 0.041). These results indicate that fosinopril at a once daily dose of 20 mg provides a sustained 24h BP reduction associated with BP reduction during physical exercise. These effects have been obtained without altering diurnal BP profile, without excessive hypotension at the time of maximal antihypertensive effect and with a slight improvement of exercise tolerance.

Adult↗
PubMed1993

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.

Animals↗
PubMed1993

Tricyclic heteroaromatic systems 1,2,4-triazolo[1,5-a]quinoxalines: synthesis and benzodiazepine receptor activity.

The synthesis, the benzodiazepine binding activity and the "in vitro" biological effect of some 1,2,4-triazolo[1,5-a]quinoxalines, 3-aza-analogues of some previously reported pyrazolo[1,5-a]quinoxalines, are described. Molecular modelling is used to define the structural requirements of the benzodiazepine recognition site which influence the affinity and different efficacy of these rigid ligands.

Animals↗
PubMed1993

Reaction of 1-aminophthalazines with alpha-halocarbonyl compounds: imidazo[2,1-a]phthalazines and their benzodiazepine receptor activities.

The one-pot synthesis and the benzodiazepine receptor binding activity of some imidazo[2,1-a]phthalazines bearing different substituents at position-2 and/or 3 and/or 6 is reported. The dissimilar binding results of the reported compounds are discussed in relation to the nature and/or position of the substituents on the tricyclic ring system.

Animals↗
PubMed1992

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.

Animals↗
PubMed1991

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.

Animals↗
PubMed1991

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. The real separation was confirmed by enzymatic tests carried out on spots of D and L forms scraped from the chromatographic plates. Total radioactivity of 14C-labeled D- and L-lactic acids was recovered. A Cu/lactic acid complex is evidenced.

Acetone↗
PubMed1991

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.

Animals↗
PubMed1990

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. Comparison of the latter results with those on previously reported compounds suggests that there are several hydrophobic regions on the benzodiazepine recognition site whose occupation gives rise to different affinity and efficacy.

Animals↗
PubMed1989

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.

Animals↗