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P Seneci

Publications and source records attributed to P Seneci.

12 recordsLinked to original sources
PubMed2001

Stereoselective synthesis of conformationally constrained cyclohexanediols: a set of molecular scaffolds for the synthesis of glycomimetics.

The practical, stereoselective synthesis of the three diastereoisomeric 1,2-trans-dicarboxy-4,5-cyclohexanediols 1-3 (DCCHDs) is described, starting from a common precursor, easily available in both enantiomeric forms. The regioselective derivatization of all functional groups of 1 is also reported. The three DCCHDs are locked in a single chair conformation and thus can be used to mimic vicinally disubstituted monosaccharides of any relative configuration.

Cyclohexanols↗
PubMed2000

Studies on the novel anti-staphyloccal compound nematophin.

A number of analogues of the recently described compound nematophin were prepared and studied for antibacterial activity. The 2-phenyl derivative was found to exhibit exceptional activity against methicillin resistant Staphylococcus aureus (MRSA) whereas the isosteric benzimidazole analogue was much less active.

Anti-Bacterial Agents↗
PubMed2000

Solid-phase/solution-phase combinatorial synthesis of neuroimmunophilin ligands.

A novel solid-phase/solution-phase strategy for the synthesis of neuroimmunophilin ligands based on GPI 1046 was developed. The synthesis employs a solid-phase esterification strategy followed by a solution-phase pyruvic amide formation to produce multi-milligram quantities of discrete compounds for assay. The protocol was applied to a production library of 880 discrete compounds. A highlight of the strategy is an aqueous extractive purification of the final compounds using a novel liquid/ice extraction system developed for high throughput.

Combinatorial Chemistry Techniques↗
PubMed2000

Combinatorial chemistry and high-throughput screening in drug discovery: different strategies and formats.

Different strategies for the discovery of novel leads interacting with therapeutically relevant targets are thoroughly presented and discussed, using also three recent examples. Emphasis is given to approaches which do not require extensive resources and budgets, but rather prove how cleverness and creativity can provide active compounds in drug discovery.

Combinatorial Chemistry Techniques↗
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↗
PubMed1996

Transport of the antibacterial agent oxazolidin-2-one and derivatives across intestinal (Caco-2) and renal (MDCK) epithelial cell lines.

The transepithelial passage of the orally bioavailable antibacterial agent oxazolidin-2-one (OXa) and 10 derivatives has been studied with human intestinal (Caco-2) and canine renal (MDCK) cell lines grown on polycarbonate filters. The transepithelial passage was assayed in the apical-to-basolateral (AP-to-BL) direction and in the opposite direction (BL to AP) in both cell lines. The observed passage rates of OXa were similar in both directions in the two cell lines, suggesting passive diffusion. This was further confirmed by the fact that transport kinetics were linear as a function of initial concentration. The rates of AP-to-BL passage of OXa and seven of the derivatives in both cell lines were linearly related to lipophilicity, whether expressed as high-passage liquid chromatography retention time or as the logarithm of the n-octanol-water partition coefficient (log P). These data suggest that the lipophilicity of OXa is important for its observed bioavailability after oral administration. Interestingly, three of the derivatives exhibited a higher passage rate than predicted by lipophilicity. Further studies indicated that this transport was saturable, similar in the two directions, and not affected by energy depletion, suggesting the presence of an additional carrier-mediated facilitated-transport mechanism.

Animals↗
PubMed1992

Synthesis and biological activity of O56-substituted carboxyesters and carboxamides of teicoplanin aglycone.

A series of O56-substituted carboxyester or carboxyamide derivatives of deglucoteicoplanin (TD) was prepared by condensation of the 56-hydroxyl function with various alkylating agents of general formula RBr, where R represents functional groups with different physico-chemical properties. The modifications at position 56 influenced the antimicrobial activity of the new derivatives; activity depended on the structure of various R groups, their ionic properties, and their steric hindrance. The activity of the new compounds did not show any significant improvement when compared with TD. The physico-chemical and antibacterial properties of the synthesized compounds are reported.

Anti-Bacterial Agents↗
PubMedDate not supplied

A combinatorial approach to [1,5]benzothiazepine derivates as potential antibacterial agents.

[1,5]Benzothiazepines are widely used in a number of different therapeutic areas and therefore represent an interesting scaffold for de novo exploration. Recent literature reports suggest their value as antibacterial agents. The present paper reports the exploration of this scaffold for the generation of combinatorial libraries both in solution and on solid phase.

Anti-Bacterial Agents↗
PubMedDate not supplied

Solid-supported benzotriazoles. 2. Synthetic auxiliaries and traceless linkers for the combinatorial synthesis of unsymmetrical ureas.

Resin-bound benzotriazole chemistry applied to the solid-phase synthesis of arrays of unsymmetrical aryl ureas is described here. The chemistry assessment process, the monomer rehearsal, the preparation of a discrete library by automated parallel synthesis, the parallel purification protocol employing solid-phase scavenging, and the complete analytical characterization of the library components are also presented.

Journal Article↗
PubMedDate not supplied

Dansyl and dabsyl analytical constructs as tools for the accurate estimation of compounds in solid-phase synthesis.

The presence of dansyl or dabsyl chromogenic moieties in a solid-phase analytical construct, an assembly of linkers/spacers/sensitizers for improving analytical characterization, allows the accurate estimation of products from solid-phase synthesis by UV detection during liquid chromatography-mass spectrometry analysis in the cleavage solution. The spectroscopic properties of dansylated molecules have been evaluated to verify the "compound-independent UV absorption" necessary for using the chromophore in the accurate estimation. First, measurements on commercial dansylated compounds were made, then a series of construct-like molecules were prepared by solution-phase synthetic procedures and their UV properties were determined. Compound calibration curves were determined, and UV absorption was shown to be both proportional to the compound concentration and compound-independent. An example of a dansyl construct derivative was then prepared on a polymeric matrix, and an accurate estimation using the calibration curves was carried out in the cleavage solution. Good agreement was found between the calculated amount of released compound using the UV calibration curves and the calculated amount using both (1)H NMR and LC/chemiluminescent nitrogen detection quantitative techniques. Preliminary studies using the dabsyl moiety as an improved chromophore with higher wavelength and extinction coefficient are also reported.

Calibration↗