Discovery of imidazole vinyl pyrimidines as a novel class of kinase inhibitors which inhibit Tie-2 and are orally bioavailable.

Tie-2 is a receptor tyrosine kinase which is involved in angiogenesis and thereby growth of human tumours. The discovery and SAR of a novel class of imidazole-vinyl-pyrimidine kinase inhibitors, which inhibit Tie-2 in vitro is reported. Their synthesis was carried out by condensation of imidazole aldehydes with methyl pyrimidines.

The mode of antibacterial action of the novel agent ZM240304 (D-arabino-2,3,4-tris(4-chlorobenzyl) pentane-1,5-diamine).

ZM240304 is an example of a new class of antibacterial agents that is active against experimental infections in animals. The compound was demonstrated to be a membrane-active compound that disrupted the outer membrane of Gram-negative organisms and allowed the leakage of periplasmic enzymes. Respiration was inhibited and cellular ATP levels were reduced, leading to cell death.

A comparison of the accumulation of novobiocin into bacteria with its antibacterial properties.

The accumulation of novobiocin in bacteria has been compared with the MIC, inhibition of DNA biosynthesis and inhibition of the activity of isolated DNA gyrase for a range of species. There was a good correlation between MIC and the inhibition of DNA biosynthesis and DNA gyrase. Novobiocin accumulation did not correlate with any other parameter.