Volume 9 Supplement 1
Synthesis and characterization of NS-2028 analogues
© Pyriochou et al; licensee BioMed Central Ltd. 2009
Published: 11 August 2009
Compounds C was as effective and potent as NS-2028, suggesting that substituting the Br atom in position 8 with a bulkier m-trifluoromethylphenyl group does not alter the activity of NS-2028. Compound B that carries a p-methoxyphenyl group in position 8 was as effective NS2028 and ODQ, but was less potent, as it only inhibited SNP-induced cGMP formation by 43% at 0.1 μÌ, compared to >80% observed with ODQ or NS-2028 when used at the same concentration. Compound A that has an expanded oxadiazolo ring was both less potent and less effective in blocking SNP-induced cGMP production. Expanding the oxazin ring to a benzodiazepinone ring resulted in a compound (compound D) with markedly reduced inhibitory activity. Finally, compound E in which the oxadiazolo ring has been converted to a triazolo ring was devoid of any sGC inhibitory activity.
We conclude that the oxadiazolo ring of NS-2028/ODQ is of major importance for the action of this class of inhibitors.
This article is published under license to BioMed Central Ltd.