A C-nitroso compound having a molecular weight ranging from about 225 to about
1,000 (from about 225 to about 600 for oral administration) on a monomeric basis
wherein a nitroso group is attached to a tertiary carbon, which is obtained by
nitrosylation of a carbon acid having a pKa less than about 25, is useful as an
NO donor. When the compound is obtained from a carbon acid with a pKa less than
about 10, it provides vascular relaxing effect when used at micromolar concentrations
and this activity is potentiated by glutathione to be obtained at nanomolar concentrations.
When the compound is obtained from a carbon acid with a pKa ranging from about
15 to about 20, vascular relaxing effect is obtained at nanomolar concentrations
without glutathione. The compound is preferably water-soluble and preferably contains
a carbon alpha to the nitrosylated carbon which is part of a ketone group. In one
embodiment, the C-nitroso compound is obtained by nitrosylation of a conventional
drug or such drug modified to modify the carbon acid pKa thereof. When such drug
is a nonsteroidal anti-inflammatory drug, the resulting C-nitroso compound functions
as a COX-1 and COX-2 inhibitor without the deleterious effects associated with
COX-1 inhibition but with the advantageous effects associated with COX-1 and COX-2
inhibition. One such C-nitroso compound is a nitrosoketoibuprofen. A specific example
of this kind of compound is isolated as dimeric 2-[4-(-nitroso)isobutyrylphenyl]propionic
acid. In another case, the C-nitroso compound contains the moiety
##STR1##
where X is S, O or NR. One embodiment is directed to COX-2 inhibitors where
a tertiary carbon atom and/or an oxygen atom and/or a sulfur atom is nitrosylated.