Discovery of Narrow Spectrum Kinase Inhibitors: New Therapeutic Agents for the Treatment of COPD and Steroid-Resistant Asthma.

The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery.

The effect of central and planar chirality on the electrochemical and chiral sensing properties of ferrocenyl urea H-bonding receptors.

A new series of chiral ureas containing one or two redox-active ferrocene units was synthesised and studied in order to investigate the effect of planar chirality and central chirality on electrochemical chiral sensing. Binding of chiral carboxylate anions in organic solvents through H-bond formation caused a negative shift in the potentials of the ferrocene/ferrocenium (Fc/Fc(+)) couples of the receptors, demonstrating their use as electrochemical sensors in solution. While the presence of two ferrocene units gave no marked improvement in the chiral sensing capabilities of these systems, the introduction of planar chirality, in addition to central chirality, switched the enantiomeric binding preference of the system and also caused an interesting change in the appearance of some voltammograms, with unusual two-wave behaviour observed upon binding a protected prolinate guest.

Reaction of 1,1'-divinyl ferrocene with one-electron oxidants: entry into functionalised [4]ferrocenophanes and observation of an isotope-dependent chemoselectivity effect.

1,1'-Divinyl ferrocene (2) reacts with K(3)[Fe(CN)(6)] under basic biphasic conditions to give a [4]ferrocenophane (4) in good yield. Incorporating deuterium labels into the internal positions of the vinyl groups of 2 affects the chemoselectivity of the reaction; thus under identical reaction conditions, [D(2)]-2 reacts to provide a diol-functionalised [4]ferrocenophane, [D(2)]-D/L-6 in addition to the expected keto-alcohol, [D(1)]-4. Variants on this one-electron oxidative cyclisation methodology can be used to give other [4]ferrocenophanes; thus, the reaction of 2 with CuCl(2) in MeOH or iPrOH leads to dialkoxy [4]ferrocenophanes 19 and 20, respectively, whereas the reaction of 2 with benzyl carbamate in the presence of tBuOCl gives a bis(carbamate)[4]ferrocenophane, 21. Mechanisms to account for the formation of the products, the stereoselectivity, and the unusual isotope-dependent chemoselectivity in the reaction of 2 and [D(2)]-2 with K(3)[Fe(CN)(6)] are proposed.

Synthesis of an achiral isomer of lipoic acid as an anchor group for SAM formation on gold surfaces.

Isolipoic acid, a symmetrical and achiral isomer of the commonly used alpha-lipoic acid, has previously been overlooked as a tether group for the formation of self-assembled monolayers (SAMs). Here its ready synthesis through a new route and its functionalization with ferrocenyl groups for redox-active SAM formation on gold electrodes are described.

Competition between planar and central chiral control elements in nucleophilic addition to ferrocenyl imine derivatives.

Planar chirality associated with the ferrocene in ferrocenyl oximes and hydrazones bearing chiral auxiliaries effectively competes with or overrides the normally excellent stereocontrol afforded by the auxiliary in determining the diastereoselectivity of addition to the C=N bond.

An exploration of ferrocenyl ureas as enantioselective electrochemical sensors for chiral carboxylate anions.

The syntheses of a series of chiral ureas containing the redox-active ferrocene group are described. Each of these bind chiral carboxylates in organic solvents through hydrogen-bonding interactions, as evidenced by spectroscopic and cyclic voltammetry measurements, the latter allowing these guests to be electrochemically sensed in solution. The enantioselectivity in the complexation of the protected amino acid N-benzenesulfonylproline by a ferrocenylbenzyl host is high enough to allow opposite enantiomers to be distinguished by electrochemical means.