N-Hydroxyurea and hydroxamic acid inhibitors of cyclooxygenase and 5-lipoxygenase

• Published in: Bioorganic & medicinal chemistry letters 1999-04, Vol.9 (7), p.979-984
• Main Authors: Connolly, Peter J., Wetter, Steven K., Beers, Kimberly N., Hamel, Stephanie C., Chen, Robert H.K., Wachter, Michael P., Ansell, Justin, Singer, Monica M., Steber, Michele, Ritchie, David M., Argentieri, Dennis C.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Bones, joints and connective tissue. Antiinflammatory agents; Cyclooxygenase Inhibitors - chemistry; Cyclooxygenase Inhibitors - pharmacology; Dogs; Hydroxamic Acids - chemistry; Hydroxamic Acids - pharmacology; Hydroxyurea - analogs & derivatives; Hydroxyurea - chemistry; Hydroxyurea - pharmacology; In Vitro Techniques; Lipoxygenase Inhibitors - chemistry; Lipoxygenase Inhibitors - pharmacology; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00117-1

Two series of compounds ( 1 and 2) having structural features of the dual COX/5-LO inhibitor tepoxalin and the 5-LO inhibitor ABT-761 were prepared. Many of these hybrid compounds are potent COX and 5-LO inhibitors; two compounds ( 1a and 2t) inhibit eicosanoid biosynthesis in an ex vivo assay. Two series of compounds ( 1 and 2) having structural features of the dual cyclooxygenase (COX)/5-lipoxygenase (5-LO) inhibitor tepoxalin and the 5-LO inhibitor ABT-761 were prepared and tested. Many of these hybrid compounds are potent COX and 5-LO inhibitors; two compounds ( 1a and 2t) inhibit eicosanoid biosynthesis in an ex vivo assay.