McLoughlin M, Kearney A S, Palepu N R
Pharmaceutical Development, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406, USA.
J Pharm Pharmacol. 1998 Feb;50(2):127-32. doi: 10.1111/j.2042-7158.1998.tb06166.x.
SB 210661, (S)-N-hydroxy-N-[2,3-dihydro-6-(2,6-difluorophenylmethoxy)-3-benzo furanyl]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.
SB 210661，即(S)-N-羟基-N-[2,3-二氢-6-(2,6-二氟苯甲氧基)-3-苯并呋喃基]脲，是一种强效且选择性的5-脂氧合酶抑制剂。主要评估了其在水中的稳定性，以支持分析方法和制剂的研发。这些结果也为不断增长的关于N-羟基脲化合物稳定性的数据库增添了内容。将SB 210661的稳定性与另外两种含N-羟基脲的化合物齐留通和雅培-79175的稳定性进行比较，结果表明在pH > 5时存在共同的主要降解途径，而在pH < 5时存在不同的降解途径。pH > 5时的途径与N-羟基脲基团的水解一致，而对于SB 210661，pH < 5时的途径与水对N-羟基脲基团的特定酸催化亲核取代一致。
