N,N'-Propylenedinicotinamide (
Nicaraven) is presently being developed for the treatment of
cerebral stroke including
subarachnoid hemorrhage. This
drug is promising because some data suggest it to have an ability to scavenge the
hydroxyl radical under physiological conditions in vivo, while it also has a high permeability through the blood brain barrier. Using the kinetic constant of the reaction between the
hydroxyl radical and
dimethyl sulfoxide, the formula derived by Babbs and Griffin (Free Rad. Biol. Med., 6 1989) was applied to obtain the kinetic constant of
Nicaraven with the
hydroxyl radical using a
dimethyl sulfoxide-
xanthine oxidase-
hypoxanthine-Fe system, and this yielded the kinetic constant 3.4x10(9) M(-1) s(-1) (1 M=1 mol dm(-3)) for
Nicaraven. Structurally related compounds were also investigated. The
amide group of
Nicaraven was thus found to play an important part in the reaction with the
hydroxyl radical.
Methanesulfinic acid, which was obtained from the reaction between
dimethyl sulfoxide and the
hydroxyl radical, was found to be stable under this adopted experimental condition and therefore was used to quantify the kinetic constant of
Nicaraven. The structure of
Nicaraven has also been investigated in CDCl3 using IR spectra, computer calculations and 1H-NMR analysis, and
Nicaraven was thus shown to have an intramolecular hydrogen bond which forms a 7-membered ring that resembles a part of the 1H-1,4-benzodiazepines. This structure may play an important role in the penetration through the blood brain barrier.