Open AccessAqueous Stability of SB 210661: Kinetics and Primary Degradation Mechanisms of an N ‐Hydroxyurea‐containing 5‐Lipoxygenase Inhibitor
Author(s) -
MCLOUGHLIN MARTIN,
KEARNEY ALBERT S.,
PALEPU NAGESH R.
Publication year - 1998
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/j.2042-7158.1998.tb06166.x
Subject(s) - zileuton , chemistry , aqueous solution , hydrolysis , kinetics , lipoxygenase , nucleophile , urea , medicinal chemistry , arachidonate 5 lipoxygenase , biochemistry , enzyme , organic chemistry , catalysis , physics , quantum mechanics , arachidonic acid
SB 210661, ( S )‐ N ‐hydroxy‐ N ‐[2,3‐dihydro‐6‐(2,6‐difluorophenylmethoxy)‐3‐benzofuranyl]urea, is a potent and selective inhibitor of 5‐lipoxygenase. Its aqueous stability was primarily evaluated to support development of analytical methods and formulations. The results also add to the growing database on the stability of N ‐hydroxyurea compounds. Comparison of the stability of SB 210661 with that of two other N ‐hydroxyurea‐containing compounds, zileuton and Abbott‐79175, supported a common primary degradative pathway at pH > 5 and different degradative pathways at pH < 5. The pathway at pH > 5 is consistent with the hydrolysis of the N ‐hydroxyurea group, whereas for SB 210661, the pathway at pH < 5 is consistent with specific acid‐catalysed nucleophilic displacement of the N ‐hydroxyurea group by water.