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Biomedical subjects

I Giorgi

Publications and source records attributed to I Giorgi.

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

New chiral inhibitors of induced platelet aggregation: the enantiomeric specificity of (R)- and (S)-methyl and ethyl esters of 1-(4-[(1-hydroxycarbonyl)-ethoxy]-benzyl)-1H-1,2,3-triazole as a tool for determining their biological target.

The synthesis of title enantiomers was accomplished and their biological behaviour as inhibitors of rabbit platelet aggregation process induced by ADP and arachidonic acid was determined. Structure-activity comparison with that of SM-12502 [(2R,5S)-(+) 3,5-dimethyl-2-(3-pyridyl)-thiazolidin-4-one hydrochloride] and Dazoxiben [4-[2-(1H-imidazol-1-yl)-ethoxy]-benzoic acid] allowed us to formulate the possible capability for the synthesized compounds to interact with the biological targets of the model molecules.

Adenosine Diphosphate↗
PubMed1995

Xanthine oxidase (XO). 4(5)-aminosubstituted-5(4)-carboxyamido-1H-1,2, 3-triazoles: a new class of monocyclic triazole inhibitors.

The 4(5)-aminosubstituted-5(4)-carboxyamido-1H-1,2,3-triazoles constitute a new class of monocyclic compounds as effective inhibitors of XO. In the past to these compounds the structure of 9-unsubstituted-8-azahypoxanthines was wrongly attributed. However some 8-azahypoxanthines obtained via a new annulation reaction have been described in this paper. The inhibitory activity of the title triazoles resulted greater than that shown by the corresponding 8-azahypoxanthines. The inhibitory competitive activity of 4(5)-n-pentyloxyoxalylamino-5(4)-carbamoyl-1H-1,2,3-triazole toward the oxidation of 8-n-pentylhypoxanthine disclosed that only one lipophilic pocket is present within the enzyme.

Molecular Structure↗
PubMed1995

Synthesis of new N(6)-substituted 2-phenyl-8-azaadenosines. Their affinity for adenosine A1 and A2 receptors. A comparison with the corresponding 2-phenyl-9-benzyl-8-azaadenines. VI.

Comparison of the affinity towards adenosine receptors of 2-phenyl-8-azaadenosines, bearing a lipophilic substituent on N(6), with the corresponding 2-phenyl-8-azaadenines was carried out. The compounds have good A1 affinity and high A1 selectivity. The obtained Ki(rib)/Ki(benz) ratios for A1 receptors, which showed variable values depending on the structure of the N(6) substituent, confirmed that 2-phenyl-8-azaadenines are characterized by greater freedom inside A1 receptors. This situation may be a favourable test of the hypothesized double disposition of these exogenous molecules within A1 receptors.

Adenine↗
PubMed1995

1,2,3-triazole[4,5-d]pyridazines--IV. Preparation and adenosine receptor binding of new 4 and/or 7 aminoderivatives.

This paper reports the continuation of the studies on the 4-aminosubstituted 1,2,3-triazole[4,5-d]pyridazine derivatives which had shown binding affinity towards adenosine receptors. Biological results confirmed the greater activity of a benzyl substituent in the 1 position and the receptorial stereoselectivity related to the higher and more selective A1 affinity of the 4-D(+)-alpha-methylbenzylamino enantiomer 1b. The 4-phenylhydrazino substituent has shown an interesting binding activity about equipotent towards A1 and A2 receptorial sites. A surprisingly elevated A1 affinity (Ki = 7 nM), 440 fold higher than A2 affinity, is presented by compound 1d, bearing a m-toluidino substituent.

Animals↗
PubMed1995

N(6) or N(9) substituted 2-phenyl-8-azaadenines: affinity for A1 adenosine receptors. VII.

The A1 activities shown respectively by N(6) or N(9) substituted 8-azaadenines were compared. At least in some cases, the biological results indicated the ability of the receptor to accept the exogenous molecule in various arrangements, and an attempt to rationalizing these arrangements was made by means of a model with two different molecular orientations.

Adenine↗
PubMed1994

2-Aryl-8-azaadenosines: structure-activity relationships in the binding with A1 and A2 receptors. A comparison with the corresponding 9-benzyl-8-azaadenines. III.

Several title compounds were assayed to determine their relative affinity towards the adenosine receptors. Selectivity ratios (SR) showed a prevalent A1 affinity. The comparison with the selectivity ratios of the corresponding 9-benzyl-8-azaadenines and the comparison between the affinity constant values (K1) for each receptor of the two series, were performed. The results led us to conclude that A1 receptors are characterized by more different arrangements which regard especially to 9-benzyl-8-azaadenines.

Adenine↗
PubMed1994

1,2,3-Triazole[4,5-d]pyridazines--II. New derivatives tested on adenosine receptors.

This paper reports the synthesis and biological evaluation towards A1 and A2 adenosine receptors of new 1,2,3-triazole[4,5-d]pyridazines bearing lipophilic substituents in the 1 position. Some 1-benzyl-4-substituted amino derivatives were prepared and the cyclohexylamino-, anilino- and p-toluidino- derivatives showed an interesting moderately selective activity on the A1 receptor.

Animals↗
PubMed1994

N(6)-substituted 2-phenyl-9-benzyl-8-azaadenines. Affinity for adenosine A1 and A2 receptors. A comparison with 2-N-butyl analogous derivatives. V.

The title compounds were prepared to evaluate their affinity towards adenosine A1 and A2 receptors. Some 2-phenyl-N(6)-substituted-8-azadenines showed good binding properties and good A1 selectivity. The biological results allow us to confirm the presence in A1 receptors of a third lipophilic pocket, able to receive the substituent on N(9), and to evince increased affinity when a phenyl group on C(2) substitutes an n-butyl group. These affinity differences between analogous 2-n-butyl and 2-phenyl derivatives indicate that they arrange themselves within A1 receptors in a similar manner and suggest that this receptor is able to arrange 8-azaadenines, bearing three lipophilic substituents, in two different ways.

Adenine↗
PubMed1994

1,2,3-triazole[4,5-d]pyridazines. III--Synthesis of new 4-amino derivatives and their affinity toward adenosine receptors.

This paper describes the preparation and adenosine receptor binding of new 1-benzyl-4-aminosubstituted-1,2,3-triazole[4,5-d]pyridazines and of other 4-aminoderivatives bearing in the 1 position other neutral substituents. The synthetic procedures consist of nucleophilic displacement reactions from the 4-chloro derivative (procedure 1), of displacement of O-sililated intermediates (procedure 2) and of the use of phosphorus pentoxide-triethylamine hydrochloride reagent (procedure 3). The A1 adenosine receptor affinity is confirmed for the 1-benzyl substituted compounds bearing in the 4 position an arylamino or cycloalkylamino group. In addition, the compound obtained by reaction with racemic alpha-methylbenzylamine shows an interesting A1 activity, unlike the 4-benzylamino derivative.

Amines↗
PubMed1993

Studies on specific inhibition of benzodiazepine receptor binding by some C-benzoyl-1,2,3-triazole derivatives.

Certain new (1-15) or previously described (16-25) 1,2,3-triazole derivatives, characterized by a C-benzoyl substituent, were synthesized and tested for their ability to displace [3H]flunitrazepam from bovine brain membrane. Compounds 11a and 9a, bearing neutral and lipophilic substituents (phenethyl and cyclohexyl, respectively) showed the higher activity. The 5-benzoyl isomer 11b presented a lower activity, equivalent to that of the triazole acetic derivative 23, which is 4-benzyl substituted. Generally, the carboxymethyl radical in the 1-position of the triazole ring decreased the activity, probably because of intramolecular hydrogen bonding with the carbonyl function of the benzoyl substituent. The N-1 unsubstituted triazole derivatives 24 and 25 were ineffective; this result is in disagreement with our previous observations. Probably these molecules interact with the receptor site by a hydrogen bonding acceptor group and by a bulky and lipophilic portion or a hydrogen bonding donor function that is appropriately arranged.

Animals↗
PubMed1993

1,2,3-Triazole[4,5-d]pyridazines--I. Analogues of prostaglandin synthesis inhibitors.

This paper reports the preparation of new triazolepyridazine derivatives bearing in the 1 position an acidic substituent, on the basis of a working hypothesis relating these compounds to 1,2,3-triazole derivatives, effective in vitro inhibitors of the prostaglandin synthesis. The tested compounds were lacking of biological activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1993

Xanthine oxidase (XO): relative configuration of complexes formed by the enzyme, 2- or 8-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines. XII.

Several 2- or 8-n-alkyl-hypoxanthines and a 2,8-di-n-pentyl-hypoxanthine were synthesized and tested as substrates or inhibitors of Xanthine Oxidase (XO). 8-Alkyl derivatives showed a substrate behaviour, whereas 2-alkyl substituted compounds were non-substrates and inhibitors. 2,8-di-n-pentyl-hypoxanthine was ineffective as inhibitor. The comparison between their activity allowed us to conclude that the complexes formed by the enzyme and the cited n-alkylhypoxanthines or 2-n-alkyl-8-azahypoxanthines involve their N(3) and N(9) positions in all the cases. The position of the n-alkyl chain determines the disposition of the molecule inside the complex: 2-n-alkyl-hypoxanthines and 2-n-alkyl-8-azahypoxanthines gave complexes with the same orientation of heterocyclic moieties, opposite that given by 8-n-alkyl-hypoxanthines.

Animals↗
PubMed1992

Psychological Effects of Vertical Banded Gastroplasty on Pathologically Obese Patients.

For a period of 2 years the authors have examined on 16 pathologically obese patients the psychological effects of the weight loss resulting from vertical banded gastroplasty. At the time of surgery the patients' average age was 41 years. The patients' average weight of 125.9 kg (range 110-150 kg) decreased after surgery to 89 kg, showing a decrease of 36.9 kg (range 20-69 kg). The postoperative compliance has been good despite the fact that the remaining gastric capacity allows for the ingestion of only 50-70 ml of food. Psychological results, obtained through consultations, semi-structured interviews and a series of tests, brought to light remarkable changes directly proportional to the weight loss achieved. Psychic well-being, self-esteem, and improvements in the interpersonal relations within the family and work environments represent in summary the positive results of the weight loss achieved by patients with no other possibility (voluntary) to keep their food intake under control (which we termed 'food addiction'). The patients abandon their depressive traits and achieve a degree of confidence that preserves them from stress and anxiety. Patients improve their social mobility, and for many the sexual relations with the partner become more frequent and intense. The weight loss plays an indispensable role within itself but additionally is associated with a general normalization of all physical parameters. Also, it starts an avalanche of positive events which break the vicious cycle: aesthetic inadequacy-anxiety/depression-food-excess weight.

Journal Article↗
PubMed1992

Synthesis and ADA inhibitory activity of new 2-aryl-8-azaadenosines. VIII.

Title compounds were synthesized from the protected beta-D-ribofuranosyl-1-azide, the sodium salt of malononitrile and the suitable aroyl nitrile. The deblocked 8-azaadenosines had shown good activity as inhibitors of adenosine deaminase (ADA) and a non-substrate behaviour toward the hydrolytic deamination promoted by the enzyme.

Adenosine↗
PubMed1992

Structure-activity studies on a 1,2,3-triazole derivative, a potent in vitro inhibitor of prostaglandin synthesis: the role of the heterocyclic ring.

This paper reports further structural modifications concerning the 1,2,3-triazole ring of the compound A, an effective in vitro inhibitor of prostaglandin synthesis. The introduction of different heterocyclic rings provided further information about of the role of the heterocyclic ring in enzymatic inhibition, as regards the number and position of the nitrogen atoms, the electronic effects, basicity, steric hindrance and hydrophilicity. The benzimidazole derivative 4e proved to possess a high enzymatic inhibitory activity.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1992

An 1,2,3-triazole derivative bioisoster of a potent in vitro prostaglandin synthesis inhibitor: preparation and biological activity.

This paper reports the preparation of the triazole ester 10, a methylenic bioisoster of an oxygenated compound A, effective inhibitor of the prostaglandin synthesis in vitro. Biological evaluation of 10 and of the corresponding acid 9 shows that the compounds maintain a good enzymatic inhibitory activity compared with indomethacin and aspirin.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1990

In vitro inhibitors of prostaglandin synthesis: (p-thiosubstituted)-benzyl nitrogen heterocycles.

This paper reports the preparation of some (p-thiosubstituted)-benzyl (disulfides, thiols, and ethyl 2-mercaptopropionates) nitrogen heterocycles (1,2,3-triazole, imidazole, pyridine, tetrazole and 1,3,4-oxadiazole) and the evaluation of their inhibitory activity of in vitro prostaglandin synthesis. The mercaptopropionates, isosters of previously studied and very effective oxyderivatives, maintain high enzyme activity which is also present, although to a lower degree, in the corresponding disulfides.

Anti-Inflammatory Agents, Non-Steroidal↗