2-Hydroxyphenyl-substituted isoxazoles, the use thereof as pharmaceutical agents and pharmaceutical compositions containing them

• Main Authors: NUHN, PETER, HABIL, O-7027 LEIPZIG, DE, RUNGE, HANS-JOACHIM.NAT., O-3033 MAGDEBURG, DE, KUPFER, CORNELIA, O-7027 LEIPZIG, DE, LUECKE, PETER.NAT., O-3090 MAGDEBURG, DE, MARSCHNER, FRANK, O-3035 MAGDEBURG, DE, KAESTNER, GERD, O-3033 MAGDEBURG, DE
• Format: Patent
• Language: English; German
• Published: 10.11.1994
• Edition: 5
• Subjects: HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

Pharmaceutical developments to date directed at lipoxygenase-mediated arachidonic acid metabolism have concentrated almost exclusively on 5-lipoxygenase, and the described inhibitor substances entail complicated synthetic routes. Recent research results indicate that leukotriene B4, which is formed by the action of LTA4 hydrolase, plays a crucial role in certain pathophysiological processes and accordingly inhibition thereof promises therapeutic applicability. 2-Hydroxyphenyl-substituted isoxazoles of the general formulae I and II have the property of inhibiting 5-lipoxygenase and/or other enzymes of the arachidonic acid cascade, such as LTA4 hydrolase. These compounds can be prepared simply by reacting 1,3-diketones (dibenzoylmethanes) or 1,2-dibromopropanones (chalcone dibromides) with hydroxylamine. The compounds according to the invention are used as active ingredients of pharmaceutical products with broad therapeutic applicability, for example for the therapy and prophylaxis of bronchial asthma, psoriasis, inflammatory and allergic disorders. where R and X have the meaning stated in Claim 1.i