John H. Dodd

Imidazopyrimidines, potent inhibitors of p38 MAP kinase.

The MAP kinase p38 is implicated in the release of the pro-inflammatory cytokines TNF-alpha and IL-1 beta. Inhibition of cytokine release may be a useful treatment for inflammatory conditions such as rheumatoid arthritis and Crohns disease. A novel series of imidazopyrimidines have been discovered that potently inhibit p38 and suppress the production of TNF-alpha in vivo.

Potent inhibitors of the MAP kinase p38.

The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.

Synthesis of RWJ 68354: A potent inhibitor of the MAP kinase p38

Abstract The regiospecific synthesis of RWJ 68354, a potent inhibitor of the p38 MAP kinase, via a variation of the Bischler-Mo¨hlau indole synthesis is reported.

The development of novel and selective p56lck tyrosine kinase inhibitors

Early T-cell receptor mediated signal transduction involves the activation of several tyrosine protein kinases. One of these tyrosine kinases, p56lck, is expressed primarily in T-cells and Natural Killer (NK) cells and has been shown to be critical for their proliferative and effector functions. Indandiones have been identified as a potent and selective chemical class that inhibits p56lck.

Stereoselectivity in the rhodium(II) acetate catalysed cyclopropanations of 2-diazo-1-indanone with styrenes

Abstract The rhodium(II) acetate catalysed cyclopropanation reactions of 2-diazo-1-indanone 4 with various substituted styrenes 5 have been investigated. The cyclopropane diastereomer 6a bearing a trans relationship between the carbonyl and the aryl ring was in all cases the predominant isomer and the ratio of stereosiomers almost constant over a range of styrene substituents. Styrenes bearing electron-donating substituents gave slightly better stereoselectivity in favour of the trans isomer. These results are substantiated by a mechanistic proposal.