[Chemistry of 1,2,5-oxadiazole. 3. Synthesis and properties of 3-methyl-4-(dialkylaminoacetyl)aminofurazan and of 3-phenyl-4-(dialkylaminoacetyl)aminofurazan].
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Amides↗
Biomedical subjects
A Gasco
Publications and source records attributed to A Gasco.
[Chemistry of 1,2,5-oxadiazole. (IV)(1). Synthesis and properties of alkyl N-(3-methylfurazan-4-yl) carbamates].
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Carbamates↗
No-mimetic furoxans: arylsulphonylfuroxans and related compounds.
A new class of methylfuroxans and methylfurazans arylthio, arylsulphinyl and arylsulphonyl substituted, characterized by vasodilating and antiaggregatory properties, is described. Vasodilating activity, tested on rabbit aortic rings percontracted with 1 microM noradrenaline, is enhanced by N-oxidation of the furazan ring and is maximized by increase of the sulphur atom oxidation level. Compounds 4-methyl-3-(p-methoxyphenylsulphonyl) furoxan 6c, 3-phenyl-4-phenylsulphonylfuroxan 10, 4-phenyl-3-phenylsulphonylfuroxan 11 and 3,4-bis(phenyl-sulphonyl)furoxan 12 (EC50 values ranging between 0.055-1.07 microM), seem to be promising since they show the highest potency as well as maximal efficacy, causing complete reversal of noradrenaline induced contraction. The structure-activity relationship, observed in the platelet aggregation test, is substantially similar to that reported for the vasodilating activity, in line with the general profile of these drugs as putative NO-mimetic derivatives.
Animals↗
SAR studies on H2 antagonists containing alkylamino substituted 1,2, 5-thiadiazole 1-oxide moieties.
A number of ranitidine analogues in which the diamino-1,2,5-thiadiazole 1-oxide substructure bearing alkyl chains of different length is present as the urea equivalent group, were synthesised and studied for their lipophilic and H2 antagonist properties. Derivatives which displayed a logP < or = 3 behaved as competitive antagonists of histamine at H2 receptors present on guinea pig right atrium. The remaining more lipophilic members of the series showed an insurmountable antagonism not completely reversible after prolonged washing. A binding study suggested that an increase in the length of alkyl chain gave rise to hydrophobic interactions with the receptor which were responsible for the apparent irreversible H2 antagonism shown by the higher homologues of the series.
Animals↗
Antisecretory and gastroprotective activities of compounds endowed with H2 antagonistic and nitric oxide (NO) donor properties.
In spite of the well recognized gastric antisecretory activity, the gastroprotective potential of histamine H2 receptor antagonists is controversial. Most clinical studies in fact indicate that these drugs do not substantially protect the gastric mucosa from aggressive factors. Nitric oxide (NO) has been recently recognized as a fundamental mediator in gastric defence mechanisms, due to its ability to increase gastric mucosal blood flow and mucus production and to inhibit neutrophils adherence to endothelial cells. The aim of this study was to investigate the gastroprotective and H2 receptor antagonistic activity of a series of lamtidine analogues which contain different NO-releasing moieties (furoxan, nitroxy and nitrosothiol). These compounds were tested, in comparison with related H2 antagonists devoid of NO-donor structures, in different H2 receptor assays and in the conscious rat against 0.6 N HCl-induced gastric lesions. All the compounds tested were able to antagonize histamine-mediated responses at cardiac and gastric H2 receptors; however, furoxan and nitroxy derivatives were 10-fold less potent than the analogues devoid of NO-donor properties. By contrast, NO-donor compounds were more active than reference H2 antagonists as gastroprotective agents against mucosal injury induced by 0.6 N HCl. Among the different NO-donor moieties, the furoxan group conferred to the H2 antagonist molecule the highest gastroprotective potential; this finding closely correlates with the characteristics of NO release. In conclusions, lamtidine-analogue H2 antagonists combined with NO-donor moieties are endowed with gastric antisecretory and protective activity and could be the prototypes of a new class of anti-ulcer drugs. Finally, the furoxan NO donor group seems to be the most favourable among the different moieties tested.
Animals↗
[Time in depression].
Subjective estimation of time varies according to age, to physical state and to the activity we are occupied with. The relationship between time and major depression can be considered from two different point of view. From a clinical-psychological point of view normal subjects with major depression estimate time intervals differently. Future, past and present change their meaning in major depression. These alterations cause important consequences in the cognitive structure of subjects with major depression and therefore influence depressive symptoms. On the other hand also the "biological time" is altered in major depression. Subjects with major depression suffer from many chronobiological alterations. The relationship between these two aspects are considered in the present report.
Circadian Rhythm↗