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José I Borrell

Publications and source records attributed to José I Borrell.

14 recordsLinked to original sources
PubMed2006

Effect of aza substitution on the photophysical and electrochemical properties of porphycenes: Characterization of the near-IR-absorbing photosensitizers 2,7,12,17-tetrakis(p-substituted phenyl)-3,6,13,16-tetraazaporphycenes.

The need for new photodynamic-therapy photosensitizers has stimulated the search of new families of compounds absorbing strongly in the 700-900 nm range, the region where tissue is most transparent to radiation capable to induce the photodynamic effect. Using computational chemistry techniques, 3,6,13,16-tetraazaporphycenes were previously identified as interesting target candidates. This work reports on the photophysical and electrochemical properties of selected members of this new family of macrocycles. Compared to porphycenes, the tetra-aza counterparts show stronger absorption in the near-infrared, lower-lying singlet and triplet excited states, and substantially larger internal conversion quantum yield (Phi(IC) = 0.93). Energy transfer to oxygen is observed, which results in the formation of the cytotoxic species singlet oxygen. The process is found to be reversible, consistent with a triplet-energy value close to that of singlet oxygen.

Aza Compounds↗
PubMed2006

Diethyl 2,7-dibromo-4H,5H- thieno[3,2-b:4,5-b']dipyrrole-3,6- dicarboxylate: a key intermediate for a diversity oriented synthesis of 2,7,12,17-tetraarylporphycenes.

A new Suzuki-based strategy for the synthesis of 4,4'-diaryl (or heteroaryl)-substituted 2,2'-bipyrroles (10), precursors of 2,7,12,17-tetraaryl (or heteroaryl)-substituted porphycenes, is described. Bromination of the previously described diethyl 4H,5H-thieno[3,2-b:4,5-b']dipyrrole-3,6-dicarboxylate afforded dibromo compound 19, which is the key intermediate of such strategy.

Journal Article↗
PubMed2006

Photochemical production and characterisation of the radical ions of tetraphenylporphycenes.

Both the radical anion and radical cation of 2,7,12,17-tetraphenylporphycene and of its palladium(II) complex have been produced by photochemical methods. Their electronic absorption spectrum and decay kinetics have been characterised by global analysis of the time-absorbance-wavelength matrix. The results provide deeper insight on the role of these radical ion species in the photodynamic activity of tetraphenylporphycenes.

Cations↗
PubMed2005

Design, synthesis and biological activity of acyl substituted 3-amino-5-methyl-1,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones as potential hypnotic drugs.

Among the known non-benzodiazepinic hypnotic drugs acting on the alpha1 subunit of the GABA-A receptor, Zolpidem, Zaleplon and Indiplon have showed high affinity and selectivity. Following a design methodology including pharmacophoric requirements and ADME-predicted properties, we have synthesized a library of 3-amino-4,5-dihydro-1H-pyrazolo[3,4-b]pyridin-6(7H)-ones and their N1-alkyl derivatives as new scaffolds for designing non-benzodiazepine BZ receptor ligands.

Animals↗
PubMed2004

Design and synthesis of two pyrazole libraries based on o-hydroxyacetophenones.

Two new solid-phase syntheses of substituted pyrazoles are described. The first includes supporting an o-hydroxyacetophenone on Merrifield resin, Vilsmeier-Haack formylation on the methyl group and cyclization with a substituted hydrazine to afford a pyrazole ring with two diversity centers. The second starts from o-hydroxyacetophenone supported on Wang resin, which undergoes a Claisen condensation with a carboxylic acid ester to yield a 1,3-dicarbonyl compound that cyclizes to a pyrazole using a hydrazine. Both methods have been used to synthesize two small pyrazole libraries.

Acetophenones↗
PubMed2003

Solid-phase synthesis of 2-substituted 4-amino-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidines: an example of cyclization-assisted cleavage.

An efficient solid-phase synthesis of 2-substituted 4-aminopyrido[2,3-d]pyrimidines 12 by cyclization-assisted cleavage from resin is reported. The procedure starts by solid supporting an alpha,beta-unsaturated acid 8 to the Wang resin 13 by using DCC and 4-DMAP in THF. The resulting alpha,beta-unsaturated ester 14 is converted to the Michael adduct by treatment with malononitrile in NaOMe/THF. Such Michael addition constitutes the first example of a Michael reaction with malononitrile in solid-phase. Finally, the Michael adducts 15 are treated with an amidine system in MeOH to yield the corresponding pyridopyrimidines 12. Compounds 12 present three diversity centers R1, R2 and G. Having validated the chemistry on solid support, a 40-membered combinatorial library was obtained using this protocol.

Combinatorial Chemistry Techniques↗
PubMed2003

A one-pot microwave-assisted synthesis of pyrido[2,3-d]pyrimidines.

A high yield multicomponent reaction providing multifunctionalized pyrido[2,3-d]pyrimidines with up to four diversity centers in a one-pot microwave-assisted cyclocondensation of alpha,beta-unsaturated esters, amidine systems and malononitrile (or ethyl cyanoacetate) is described.

Algorithms↗
PubMed2003

Solid-phase synthesis of 2-substituted 4-amino-7-oxo-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidines.

An efficient solid-phase synthesis of 2-substituted 4-aminopyrido[2,3-d]pyrimidines 15 is reported. The procedure started by solid supporting a p-hydroxybenzaldehyde 8 to the Wang resin by using the Mitsunobu protocol. The resulting aldehyde 17 was treated with a substituted acid methyl malonate 10 to afford the corresponding alpha, beta-unsaturated ester 18, which was converted to the Michael adduct 21 by reaction with malononitrile. Cyclization of 21 with an amidine system 13 yielded the solid supported pyridopyrimidine 22, which afforded the corresponding 2-substituted 4-aminopyrido[2,3-d]pyrimidine 15 upon treatment with TFA:DCM. Compounds 15 present three diversity centers R1, R2 and R3. Having validated the chemistry on solid support, a 32-membered combinatorial library was obtained using this protocol.

Combinatorial Chemistry Techniques↗
PubMed2003

Analysis of selection methodologies for combinatorial library design.

We have implemented and adapted in Pralins (Program for Rational Analysis of Libraries in silico), the most popular sparse (cherry picking) and full array (sublibrary) selection algorithms: hierarchical clustering, k-means clustering, Optimum Binning, Jarvis Patrick, Pral-SE (partitioning techniques) and MaxSum, MaxMin, MaxMin averaged, DN2, CTD (distance-based methods). We have validated the program with an already synthesized three-component combinatorial library of FXR partial agonists characterized by standard computational chemistry descriptors as case study. This has let us analyze the goodness of both the partitioning techniques for space division and all the selection methodologies with respect to representativity in terms of population and space coverage for different selection sizes. Within the chemical space analyzed, both hierarchical clustering and Optimum Binning division strategies are found to be the most advantageous reference space divisions to be used in the subsequent population and space coverage studies. Complete hierarchical clustering appears also to be the preferred selection methodology for both sparse and full array problems. The full array restriction fulfillment can easily be overcome by convenient optimization algorithms that allow optimal reagent selection preserving > 90% of the population coverage.

Combinatorial Chemistry Techniques↗
PubMed2003

Use of combinatorial chemistry to develop photocurable thermoplastic polyurethane elastomers (TPUs).

Combinatorial chemistry was used to develop photocurable thermoplastic polyurethane elastomers through the incorporation of photoreactive diacetylene diols as chain extenders. The methodology applied allowed, in 36 experiments, the choice of the best compromise between mechanical properties and lack of colour. The combinations chosen were scaled up and their properties were evaluated in terms of mechanical properties. The combinatorial approach reduced the estimated time tenfold in developing such type of materials.

Combinatorial Chemistry Techniques↗
PubMed2002

Preparative-scale synthesis of two metabolites isolated from soil treated with zoxium fungicide and kerb herbicide.

The preparation in multigram scale of two metabolites 3-(3,5-dichloro-4-methyl-benzoylamino)-2-hydroxy-3-methyl-pentanoic acid and 3-(3,5-dichloro-benzoylamino)-3-methyl-2-oxo-butyric acid isolated from soil treated with either Zoxium fungicide or Kerb herbicide was efficiently accomplished using a common 5-step synthetic process starting from easily available raw materials.

Amides↗
PubMedDate not supplied

2-Methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles: versatile starting materials for the synthesis of libraries with diverse heterocyclic scaffolds.

Heterocyclic demonstration libraries for agrochemical screening were prepared from the common intermediates 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles (1), using standard solution-phase techniques. A total of 18 screening libraries were prepared in good to excellent yields. Several members of these libraries were active in the first level of agrochemical screening, especially in the fungicide screen.

Chemistry, Pharmaceutical↗
PubMedDate not supplied

Design and analysis of a combinatorial library of HEPT analogues: comparison of selection methodologies and inspection of the actually covered chemical space.

A large virtual library of 125 396 HEPT analogues, built by combining all fragments present in the published 180-compound HEPT family, has been studied in terms of diversity criteria and the goodness of the 11 available standard diversity selection methods analyzed. All the algorithms under study, except Cell-based Density, have rank above a random selection of compounds, with Optimum and Standard Deviation based Binning and Cell-based Fraction algorithms being the best choices. Furthermore, analysis of the actually tested compounds has been performed to compare the traditional drug discovery methodology versus a rational selection of combinatorial libraries approach.

Journal Article↗