Synthetic cannabinoid use in an adult male prison in the UK.

Introduction: Synthetic cannabinoids (i.e. Spice) are a major public health problem in UK prisons, however, research in this area is limited.

Exploration of the nicotinamide-binding site of the tankyrases, identifying 3-arylisoquinolin-1-ones as potent and selective inhibitors in vitro.

Tankyrases-1 and -2 (TNKS-1 and TNKS-2) have three cellular roles which make them important targets in cancer. Using NAD(+) as a substrate, they poly(ADP-ribosyl)ate TRF1 (regulating lengths of telomeres), NuMA (facilitating mitosis) and axin (in wnt/β-catenin signalling). Using molecular modelling and the structure of the weak inhibitor 5-aminoiso quinolin-1-one, 3-aryl-5-substituted-isoquinolin-1-ones were designed as inhibitors to explore the structure-activity relationships (SARs) for binding and to define the shape of a hydrophobic cavity in the active site.

Digital camera measurements of soot temperature and soot volume fraction in axisymmetric flames.

New diagnostics are presented that use a digital camera to measure full-field soot temperatures and soot volume fractions in axisymmetric flames. The camera is a Nikon D700 with 12 megapixels and 14 bit depth in each color plane, which was modified by removing the infrared and anti-aliasing filters. The diagnostics were calibrated with a blackbody furnace.

One-pot tandem Hurtley-retro-Claisen-cyclisation reactions in the synthesis of 3-substituted analogues of 5-aminoisoquinolin-1-one (5-AIQ), a water-soluble inhibitor of PARPs.

Poly(ADP-ribose)polymerase-1 (PARP-1) is an important target for drug design for several therapeutic applications. 5-Aminoisoquinolin-1-one (5-AIQ) is a highly water-soluble lead compound; synthetic routes to 3-substituted analogues were explored. Tandem Hurtley coupling of β-diketones with 2-bromo-3-nitrobenzoic acid, retro-Claisen acyl cleavage and cyclisation gave the corresponding 3-substituted 5-nitroisocoumarins.

5-Benzamidoisoquinolin-1-ones and 5-(ω-carboxyalkyl)isoquinolin-1-ones as isoform-selective inhibitors of poly(ADP-ribose) polymerase 2 (PARP-2).

PARP-2 is a member of the poly(ADP-ribose) polymerase family, with some activities similar to those of PARP-1 but with other distinct roles. Two series of isoquinolin-1-ones were designed, synthesized, and evaluated as selective inhibitors of PARP-2, using the structures of the catalytic sites of the isoforms. A new efficient synthesis of 5-aminoisoquinolin-1-one was developed, and acylation with acyl chlorides gave 5-acylaminoisoquinolin-1-ones.

Synthesis of 4-alkyl-, 4-aryl- and 4-arylamino-5-aminoisoquinolin-1-ones and identification of a new PARP-2 selective inhibitor.

The considerable interest in substituted isoquinolin-1-ones related to 5-aminoisoquinolin-1-one (5-AIQ) as drugs points to a need for an efficient and straightforward synthesis of the 4,5-disubstituted bicycles. Bromination of 5-nitroisoquinolin-1-one gave 4-bromo-5-nitroisoquinolin-1-one but neither this nor 5-amino-4-bromoisoquinolin-1-one would participate in Pd-catalysed couplings. Protection of the lactam as 1-methoxy- and 1-benzyloxy-4-bromo-5-nitroisoquinolines, however, permitted Stille, Suzuki and Buchwald-Hartwig couplings to take place in high yields, insensitive to electronic demands and severe steric bulk in the arylboronic acids.

Formation of 3-aryl-5-nitroisocoumarins from 5-nitroisocoumarins and aromatic acyl chlorides under Friedel-Crafts conditions.

Treatment of 5-nitroisocoumarin with aromatic acyl chlorides under Friedel-Crafts conditions gives 3-aryl-5-nitroisocoumarins, rather than the expected 4-acyl-5-nitroisocoumarins. This procedure was optimized for reaction temperature (150 degrees C), solvent (nitrobenzene), and Lewis acid (SnCl4). Reaction of 5-nitroisocoumarin with [13C]-carbonyl benzoyl chloride under the optimum conditions gave 5-nitro-3-phenylisocoumarin in which the 13C is located at the 3-C of the heterocycle, indicating that the benzoyl carbon framework is incorporated intact.

Thin-filament pyrometry with a digital still camera.

A novel thin-filament pyrometer is presented. It involves a consumer-grade color digital still camera with 6 megapixels and 12 bits per color plane. SiC fibers were used and scanning-electron microscopy found them to be uniform with diameters of 13.