Antonio Garrido Montalban

The synthesis of aromatic diazatricycles from phenylenediamine-bis(methylene Meldrum's acid) derivatives

The thermocyclisation of phenylenediamine-bis(methylene Meldrums acid) derivatives has been investigated. Those of o-phenylenediamines give 1,10-phenanthroline derivatives, while those of m- and p-phenylenediamines lead to the preferential formation of angular diazatricycles. Thus, for example, the di-Meldrums acid derivative of 2,5-dichloro-1,4-phenylenediamine gives, via ipso-substitution, the unexpected angular product 19.

Synthesis and reactions of dipyrromethane-2,10-dicarboxylates

Abstract Dipyrromethane-2,10-dicarboxylates have been prepared. While oxidation and subsequent reaction of 5b with BF 3 ·OEt 2 yields the corresponding complex 10 , ring-closing metathesis of 5d using (NHC)(PCy 3 )(Cl) 2 RuCHPh 7 results in the novel hybrid macrocycle 8 . The structure of 10 has been unequivocally established by an X-ray crystallographic study.

Synthesis and photophysical properties of peripherally metallated bis(dimethylamino)porphyrazines

Abstract The photophysics of the two novel solitaire porphyrazines 3 and 4 (obtained via coordination of PdCl 2 and PtCl 2 to the peripheral bis(dimethylamino) entity of the Zn-porphyrazine 1 , respectively) have been examined using absorption, emission and transient absorption spectroscopy. While the free ligand 1 exhibits neither fluorescence nor triplet absorption, the peripherally metallated derivatives 3 and 4 display both fluorescence as well as intersystem crossing.

The design and synthesis of novel α-ketoamide-based p38 MAP kinase inhibitors

We have identified a novel series of potent p38 MAP kinase inhibitors through structure-based design which due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo PK studies show these compounds to have drug-like characteristics which could result in the development of an oral treatment for inflammatory conditions.

Phenanthroline-appended porphyrazines: synthesis and conversion into solitaire Ru(II) complexes

Abstract Unsymmetrical porphyrazines (tetraazaporphyrins) bearing a single bidentate phenanthroline chelating group M[pz(t-butylphenyl)6phen] have been prepared by the base-catalyzed cross condensation of 3,4-bis(4-tert-butylphenyl)pyrroline-2,5-diimine (in excess) with 6,7-dicyanodipyridoquinoxaline. Treatment of these centrally metalated (M=Mg, Zn) ligands with various Ru(II) salts has yielded several bimetallic complexes including the first coordinatively linked porphyrazine trimer. The optical properties of these complexes are shown to be a function of the additional ligands surrounding the asymmetric ruthenium center.

Synthesis, characterization and reactions of enantiomerically pure 'winged' spirane porphyrazines

Abstract A series of enantiomerically pure porphyrazineoctaol derivatives have been prepared from l -(+)-dimethyl tartrate via conversion into the corresponding dispoke protected dihydroxymaleonitrile, Linstead macrocyclization and transmetallation. The derived chloromanganese(III) complexes catalyzed the epoxidation of styrene with sodium hypochlorite as the oxygen atom source but with modest enantioselectivities (

Cerium(III) chloride mediated regioselective synthesis of cyclic α-chloro-α,β-enones and α-chloro-β-hydroxy ketones

Abstract Reaction of cyclic α,β-epoxy ketones with Ce(III) chloride under hydrous or anhydrous conditions yields the corresponding cyclic α-chloro-α,β-enones or cyclic α-chloro-β-hydroxy ketones, respectively.

Synthesis and ring opening metathetic polymerisation of porphyrazine benzonorbornadiene derivatives

Abstract Benzonorbornadiene substituted porphyrazines are homo- and copolymerised (ROMP) with norbornene using Cl 2 (Cy 3 P) 2 RuCHPh to provide dark-green and blue polymers. These novel materials have been characterised using GPC, UV-vis and EPR spectroscopy.

Optimization of α-ketoamide based p38 inhibitors through modifications to the region that binds to the allosteric site

We have optimized a novel series of potent p38 MAP kinase inhibitors based on an alpha-ketoamide scaffold through structure based design that due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME, in vivo PK and efficacy studies show these compounds to have drug-like characteristics and have resulted in the nomination of a development candidate which is currently in phase II clinical trials for the oral treatment of inflammatory conditions.

'Reverse' α-ketoamide-based p38 MAP kinase inhibitors

We have identified a second series of potent p38 inhibitors. As with our first generation series, these compounds are based on an alpha-ketoamide scaffold. The reversal of the ketoamide order, however, introduces more chemical flexibility and in addition results in improve potencies against p38.