Coronary vasospasm during an acute allergic reaction.
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Anaphylaxis↗
Biomedical subjects
L Cecchi
Publications and source records attributed to L Cecchi.
Synthesis of a set of ethyl 1-carbamoyl-3-oxoquinoxaline-2-carboxylates and of their constrained analogue imidazo.
The synthesis and glycine/NMDA and AMPA receptor affinities of a set of ethyl (+/-) 1-N-carbamoyl-1,2,3,4-tetrahydro-3-oxoquinoxaline-2-carboxylates 1-11 and those of their constrained analogue (+/-) 1,2,3,3a,4,5-hexahydroimidazo[1,5-a]quinoxaline-1,3,4-triones 12-24 are reported. Compounds 1-11 bear a side-chain at position 1 which has been spatially constrained in compounds 12-24. Most of the reported tricyclic derivatives 12-24 showed glycine/NMDA binding activity comparable to that of their corresponding bicyclic analogues 1-11 providing further evidence that the spatial orientation of the side-chain is an important structural requirement for glycine/NMDA receptor antagonists.
Animals↗
Age-related changes in the urinary excretion of aldehydes in ad libitum fed and food-restricted rats.
Age-related changes in the urinary excretion of aldehydes arising from lipid peroxidation have been investigated in male Sprague-Dawley rats aged 2, 4, 6, 12, 18, 24 and 27 months, fed ad libitum or subjected to two different regimens of calorie restriction (namely every-other-day ad libitum feeding--EOD--and 40% calorie restriction--40%DR). For only some age groups, results were compared with those obtained in ad libitum fed male Fisher 344 and Lewis rats. Results show that the urinary excretion of malondialdehyde (MDA) and formaldehyde (FA) significantly decreases, whereas that of propionaldehyde (PROP) progressively increases with age, and that urinary excretion of acetaldehyde (ACT) does not show any significant age-related variations. Dietary restriction significantly increases the urinary levels of MDA, FA and PROP without affecting their age-related modifications, and does not affect ACT urinary excretion. In conclusion, results indicate that the quantitative pattern of aldehyde production and urinary excretion may be altered by the process of aging.
Aging↗
7-Chloro-4,5-dihydro-8-(1,2,4-triazol-4-yl)-4-oxo-1,2,4-triazolo[1, 5-a]quinoxaline-2- carboxylates as novel highly selective AMPA receptor antagonists.
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Animals↗
Synthesis and structure-activity relationships of a new set of 2-arylpyrazolo[3,4-c]quinoline derivatives as adenosine receptor antagonists.
In a recent paper (Colotta et al. J. Med. Chem. 2000, 43, 1158-1164) we reported the synthesis and adenosine receptor binding activity of two sets of 2-aryl-1,2,4-triazolo[4,3-a]quinoxalines (A and B) some of which were potent and selective A(1) or A(3) antagonists. In this paper the synthesis of a set of 2-arylpyrazolo[3,4-c]quinolin-4-ones 1-10, 4-amines 11-18, and 4-amino-substituted derivatives 19-35 are reported. The binding activity at bovine A(1) and A(2A) and human cloned A(3) adenosine receptors showed that (i) the substituent on the appended 2-phenyl ring could be used to modulate A(1) and A(3) affinity, (ii) the 4-amino group was necessary for A(1) and A(2A) binding activity, and (iii) a nuclear or extranuclear C=O proton acceptor at position 4 yielded potent and selective A(3) antagonists. These results are in agreement with those of the previously reported series A and B suggesting a similar adenosine receptor binding mode. In particular, the A(3) nanomolar affinity of 1-8, 31-33, and 35 confirms the hypothesis of the presence in the N-6 region of the adenosine A(3) subtype of a proton donor able to bind to a C=O proton acceptor at position 4.
Animals↗
1,2,4-Triazolo[4,3-a]quinoxalin-1-one: a versatile tool for the synthesis of potent and selective adenosine receptor antagonists.
4-Amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo[4, 3-a]quinoxalin-1-one (1) has been found to be an A(2A) versus A(1) selective antagonist (Colotta et al. Arch. Pharm. Pharm. Med. Chem. 1999, 332, 39-41). In this paper some novel triazoloquinoxalin-1-ones 4-25 bearing different substituents on the 2-phenyl and/or 4-amino moiety of the parent 4-amino-1, 2-dihydro-2-phenyl-1,2,4-triazolo[4,3-a]quinoxalin-1-one (3) have been synthesized and tested in radioligand binding assays at bovine A(1) and A(2A) and cloned human A(3) adenosine receptors (AR). Moreover, the binding activities at the above-mentioned AR subtypes of the 1,4-dione parent compounds 26-31 and their 5-N-alkyl derivatives 33-37 were also evaluated. The substituent on the 2-phenyl ring exerted a different effect on AR subtypes, while replacement of a hydrogen atom of the 4-amino group with suitable substituents yielded selective A(1) or A(3) antagonists. Replacement of a hydrogen atom of the 4-NH(2) with an acyl group, or replacement of the whole 4-NH(2) with a 4-oxo moiety, shifted the binding activity toward the A(3) AR. The binding results allowed elucidation of the structural requirements for the binding of these novel tricyclic derivatives at each receptor subtype. In particular, A(1) and A(2A) binding required the presence of a proton donor group at position-4, while for A(3) affinity the presence of a proton acceptor in this same region was of paramount importance.
Animals↗
4,5-Dihydro-1,2,4-triazolo[1,5-a]quinoxalin-4-ones: excitatory amino acid antagonists with combined glycine/NMDA and AMPA receptor affinity.
A series of 4,5-dihydro-1,2,4-triazolo[1,5-a]quinoxalin-4-ones bearing different substituents on the benzo-fused ring and at position 2 were synthesized and biologically evaluated for their binding at glycine/NMDA and AMPA receptors. Most of the reported compounds show combined glycine/NMDA and AMPA receptor binding activity providing further evidences of the structural similarities of the binding pockets of both receptor recognition sites. Moreover, this study has pointed out some differences for the binding at each receptor type. In particular, for the glycine/NMDA receptor-ligand interaction, the presence of a free acidic function at position 2 and an electron-withdrawing substituent(s) nonbulkier than chlorine atom(s) on the benzo-fused moiety is required. Functional antagonism at the NMDA receptor-ion channel complex was also performed on some selected compounds.
Animals↗
4-Amino-6-benzylamino-1,2-dihydro-2-phenyl-1,2,4-triazolo [4,3-alpha]-quinoxalin-1-one: a new A2A adenosine receptor antagonist with high selectivity versus A1 receptors.
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Animals↗
Synthesis, glycine/NMDA and AMPA binding activity of some new 2,5,6-trioxopyrazino[1,2,3-de]quinoxalines and of their restricted analogs 2,5-dioxo- and 4,5-dioxoimidazo[1,5,4-de]quinoxalines.
The synthesis of some new 1,2,3,5,6, 7-hexahydro-2,5,6-trioxopyrazino[1,2,3-de]quinoxalines 1c-g and of their restricted analogs 2,4,5,6-tetrahydro-2,5-dioxo-1H- 2a-g and 5,6-dihydro-4,5-dioxo-4H-imidazo[1,5,4-de]quinoxalines 3a-d is reported. Compounds 1c-g, 2a-g, and 3a-d were tested for their binding activity at the glycine/NMDA and AMPA receptors. The results show that only the 6,6,6-tricyclic derivatives 1c-g are able to bind to the glycine/NMDA and AMPA receptors, although with lower affinity than the previously reported lead compounds 1a-b. In contrast, the 5,6,6-tricyclic derivatives 2a-g are inactive at both receptors and only one 4,5-dioxoimidazoquinoxaline (3b) displays a weak glycine/NMDA receptor affinity.
Animals↗
[Extranodal lymphomas. A rare clinical entity or a protean disease? A case report].
Aim of the present study is to describe a case of extranodal lymphoma localized in paravertebral site, near to thoracic spine. The clinical onset of the affection was as a radicular sciatalgic pain, resistant to long-term current therapy by NSAIDs, and determined by neuroradicular involvement by the neoplastic bulk. The interest of the present case is determined by: 1) the presence of a pain which, for a long while, mimicked one of the most trivial painful syndromes; 2) the fact that extranodal lymphomas are not so rare ones. An extensive research of such entities is therefore mandatory; 3) the diagnosis was made by means of non-invasive examination, and needle biopsy was performed only to confirm a picture which was already patent.
Biopsy, Needle↗
Synthesis of 2-substituted-6,8-dichloro-3,4-dihydro-3-oxo-2H-1,4-benzothiazine-1,1-d ioxides and -1-oxides as glycine-NMDA receptor antagonists.
A number of 2-substituted-3,4-dihydro-3-oxo-6,8-dichloro-2H-1, 4-benzothiazine-1,1-dioxides (1-2a-b) and -1-oxides (3-4a-b) bioisosters of RPR 104632 in which the 3-carboxylic group was replaced by a carbonyl group were synthesized. Comparative in vitro pharmacological studies on this series of RPR 104632 analogs were performed using receptor binding assays. None of these compounds showed detectable binding affinity for the glycine-NMDA receptor.
Animals↗
Synthesis and A1 and A2A adenosine binding activity of some pyrano[2,3-c]pyrazol-4-ones.
A series of pyrano[2,3-c]pyrazol-4-ones was synthesized and evaluated for bovine brain adenosine A1 and A2A receptor binding affinity. Substituents at positions 5 and/or 6 were varied in order to define the structure-activity relationships in these new kinds of adenosine receptor ligands. The most selective and potent ligand among the reported compounds was the 1,4-dihydro-1-phenyl-3-methyl-6-(3-aminophenyl)-pyrano[2,3-c]pyraz ol-4-one 11 which showed a 27-fold selectivity for A1 receptor and a Ki value of 84 nM.
Animals↗
A proposed mechanism of the antiaging action of diet restriction.
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Aging↗
Synthesis and biological evaluation of a series of quinazoline-2-carboxylic acids and quinazoline-2,4-diones as glycine-NMDA antagonists: a pharmacophore model based approach.
The synthesis and glycine-NMDA binding activity of a series of quinazoline-2-carboxylic acids 1 and quinazoline-2,4-diones 2, containing all the essential and optional pharmacophoric descriptors required by a putative glycine antagonist model, are reported. The binding results show that only three of the title compounds displayed micromolar receptor affinity, demonstrating how disappointing the synthesis of receptor ligands based only on interaction models can be.
Animals↗
Tricyclic heteroaromatic systems. Pyrazolo[3,4-c]quinolin-4-ones and pyrazolo[3,4-c]quinoline-1,4-diones: synthesis and benzodiazepine receptor activity.
Some pyrazolo[3,4-c]quinoline-4-ones 1-14 and pyrazolo[3,4-c]-quinoline-1,4-diones 15-17 were prepared and biologically evaluated for their binding at the benzodiazepine receptor (BZR) in rat cortical membranes. The moderate binding activity of 1-5, 7, 9-10, 13 is attributable to the lack of the optional proton acceptor at position-1, while the inactivity of the 1,4-dione derivatives 15-17 is due to the lack of the essential proton acceptor at position-3. These conclusions confirm the validity of our proposed pharmacophoric model.
Animals↗
Tricyclic heteroaromatic systems. 1,2,4-triazolo[4,3-a]quinoxalines and 1,2,4-Triazino[4,3-a]quinoxalines: synthesis and central benzodiazepine receptor activity.
Some 1,2,4-triazolo[4,3-a]quinoxalines 1-10, and 1,2,4-triazino[4,3-a]quinoxalines 11-12 were prepared and biologically evaluated for their binding at the benzodiazepine receptor (BZR) in rat cortical membranes. The BZR affinity of 1-10 demonstrates that the presence of a proton acceptor at position-1 is important for the potency of a BZR ligand. On the other hand, the BZR inactivity of the 1,2,5-trione derivatives 11-12 shows that the right collocation of the essential L2 lipophilic substituent is of paramount importance for receptor-ligand interaction.
Animals↗
Tricyclic heteroaromatic systems. 3-substituted 1,2,3,5,6,7-hexahydro-2,5,6-trioxopyrazino[1,2,3-de]-quinoxalines as novel antagonists at the glycine-NMDA site.
Two novel antagonists of the glycine-NMDA receptor have been synthesized and tested for their ability to displace [3H]glycine from its specific binding site in rat brain cortical membranes. The 3-substituted pyrazino[1,2,3-de]quinoxalin-2,5,6-triones 1a-b contain all the essential pharmacophoric descriptors of a glycine receptor antagonist. A model is proposed for the binding of these compounds that includes some of the interactions postulated for the potent glycine-NMDA receptor antagonist L-689,560.
Aminoquinolines↗
Synthesis and binding activity of some pyrazolo[1,5-c]quinazolines as tools to verify an optional binding site of a benzodiazepine receptor ligand.
The synthesis and binding activity at the benzodiazepine receptor of some 2-substituted pyrazolo[1,5-c]quinazolines are reported. The structure-activity relationships and in vitro efficacy of the title compounds, which are devoid of the proton acceptor atom at position 1, are similar to those of some previously reported tricyclic heteroaromatic compounds. This suggests that a proton acceptor at position 1 is an optional binding site of a benzodiazepine receptor ligand which only affects potency.
Animals↗