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C Marchioro

Publications and source records attributed to C Marchioro.

9 recordsLinked to original sources
PubMed2002

Analytical methods for the monitoring of solid phase organic synthesis.

Solid phase synthesis (SPS) is a powerful technique to assemble compound libraries in high-throughput parallel and combinatorial synthesis. The widespread applications of these techniques required the development of analytical methods for both structural elucidation and reaction monitoring. This review covers some recently developed techniques for on-bead analyses together with solution-state ones. Particular emphasis is devoted to software and hardware improvements for automated high-throughput analysis.

Chemistry Techniques, Analytical↗
PubMed2000

Polymer-supported silyl cyanide and silyl azide: useful reagents for solid-phase applications.

The support of a delicate reagent on a solid matrix allows for better and safer handling of the reagent itself. Because we had an interest in silicon-based supported reagents(1) we turned our attention to a polymer-supported trialkylsilyl cyanide and trialkylsilyl azide starting from a commercially available trialkylsilane resin. The supported cyanide was obtained with excellent yield and proved to be shelf-stable. This supported reagent was reacted with a series of aldehydes and ketones yielding the corresponding polymer-supported cyanohydrins in good-to-excellent yields. A stability study on a model cyanohydrin demonstrated that these supported intermediates also can be stored for a prolonged time. For the last step, a cleavage strategy that could release either cyanohydrins or alpha-hydroxy esters was adopted. Finally, we prepared a polymer-supported trialkylsilyl azide, which also proved to be shelf-stable.

Aldehydes↗
PubMed1999

Cycloalkyl indole-2-carboxylates as useful tools for mapping the "north-eastern" region of the glycine binding site associated with the NMDA receptor.

A novel series of indole-2-carboxylate analogues of GV 150526 (1) in which the terminal phenyl ring belonging to the side chain present in the position C-3 has been replaced with a bridged cycloalkyl group was synthesized and evaluated for its pharmacological profile. Modelling studies on this class of novel glycine antagonist allowed us to identify an asymmetric lipophilic pocket present in the "North-Eastern" region of the pharmacophoric model of the glycine binding site associated to the NMDA receptor. Among the derivatives prepared, 3-[2-(1-adamantylaminocarbonyl)ethenyl]-4,6-dichloroindole-2 -carboxylic acid 6b and 3-[2-(norbornylaminocarbonyl)ethenyl]-4,6-dichloroindole-2-c arboxylic acid 6l were found to be antagonists acting at the strychnine-insensitive glycine binding site, showing nanomolar affinity for the glycine binding site (Ki = 63 and 19 nM, respectively), coupled with high glutamate receptor selectivity (IC50 > 10(-5) M at the NMDA, AMPA, KA binding sites) and high in vivo potency after systemic administration by inhibition of convulsion induced by NMDA in mice.

Amantadine↗
PubMed1999

Substituted indole-2-carboxylates as potent antagonists of the glycine binding site associated with the NMDA receptor.

A novel series of indole-2-carboxylate analogues of GV150526 (1) in which the propenoic double bond was substituted with different "probes" or replaced by a isosteric cyclopropyl moiety were synthesized and evaluated for their affinity profile in order to obtain further information on the pharmacophoric model of the glycine binding site associated to the NMDA receptor.

Animals↗
PubMed1998

In vivo metabolism of a novel cholecystokinin B (CCK-B) antagonist in rat and dog plasma and rat faeces.

1. The in vivo metabolism of a novel CCK-B antagonist ((+)-N-[1-(adamantane-1-methyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H -1,5-benzodiazepin-3-yl]-N'-phenylurea, GV150013X) was investigated using rat and dog plasma (male and female) and rat faeces samples after administration of GV150013X. 2. Four monohydroxy and four dihydroxy metabolites of GV150013X were identified by comparison with authentic standards using hplc and results from previous in vitro studies. 3. In both rat and dog plasma, GV150013X was converted to one major and other minor metabolites. 4. Qualitatively there is no species or sex differences in the formation of metabolites except that minor metabolite M1 was not detected in dog plasma. 5. Traces of GV150013X and the major metabolite were seen in rat plasma sample 24 h after administration. 6. Hplc with UV and radiochemical detection was used to identify metabolites. Major, non-labelled GV150013X metabolites from rat faeces were collected for characterization by nmr.

Adamantane↗
PubMed1994

Magnetic resonance spectroscopy investigations of brown adipose tissue and isolated brown adipocytes.

Brown adipose tissue and collagenase-isolated brown adipocytes were investigated in rats by means of 1H and 13C nuclear magnetic resonance spectroscopy. After chloroform-methanol extraction of brown adipose tissue, proton and natural abundance 13C spectra of the chloroform fraction showed resonances attributable to triglycerides, and were qualitatively similar to those of the corresponding fraction of white adipose tissue. By means of quantitative analysis of 1H spectra, fatty acid unsaturation and polyunsaturation in triglycerides were found to be lower in brown than white adipose tissue; moreover, unsaturation parameters decreased in triglyceride fatty acids of brown adipose tissue upon norepinephrine administration or cold acclimatization of rats, and were affected by the age of donors. The molar percentage of mono- and polyunsaturated C18 fatty acids in triglycerides was determined from 13C spectra and found to change in the early post-natal period. Isolated, agarose-embedded brown adipocytes from 4-day-old rats showed a number of peaks in the carbohydrate region of 1H spectra that were not present in spectra of white adipocytes and almost disappeared in brown fat cells of older animals. These peaks could be restored by insulin exposure. Natural abundance 13C spectra of isolated brown adipocytes were resolved enough to allow unambiguous assignment of resonances to carbons of fatty acids, glycerol, glucose, ethanolamine, and choline. Calculation of the mono- to polyunsaturated fatty acids ratio in the cells was also performed. Nuclear magnetic resonance spectroscopy is a useful tool for the investigation of brown adipose tissue and adipocytes therefrom.

Acclimatization↗
PubMed1993

Synthesis and antimicrobial activity of DNA-gyrase inhibiting derivatives of 4-oxo-1,4-dihydro-3-pyridinecarboxylic acid.

A series of 6-substituted-1-aryl-4-oxo-1,4-dihydronicotinic acids were synthesised as monocyclic analogues of the quinolones. The 6-(2-aryl-1-methylethenyl)- and of the 6-(2-arylethenyl)-substituted compounds were shown to possess antibacterial properties that correlate with DNA gyrase inhibitory activity. Differently from the quinolones the antimicrobial activity of the compounds of this study is predominantly against Gram positive strains. The structure-activity relationships ascertained for these monocyclic compounds differ from those established for the quinolones.

Anti-Bacterial Agents↗