Differential effects of a series of hydroxamic acid derivatives on 5-lipoxygenase and cyclooxygenase from neutrophils and 12-lipoxygenase from platele...

ID: ALA1124558

Journal: J Med Chem

Title: Differential effects of a series of hydroxamic acid derivatives on 5-lipoxygenase and cyclooxygenase from neutrophils and 12-lipoxygenase from platelets and their in vivo effects on inflammation and anaphylaxis.

Authors: Huang FC, Shoupe TS, Lin CJ, Lee TD, Chan WK, Tan J, Schnapper M, Suh JT, Gordon RJ, Sonnino PA.

Abstract: The synthesis of a series of novel substituted hydroxamates has been described along with their profile of inhibitory activity against 5-lipoxygenase, 12-lipoxygenase, and cyclooxygenase enzymes. The structure--activity relationship suggests that future molecules could be designed to specifically inhibit one or more of these enzymes since there were definite differences in structure--activity relationships for these different enzymes. A representative number of these compounds have been tested in vivo and found to possess potent oral activity in a systemic anaphylaxis model mediated by leukotrienes and topical activity in an arachidonic acid induced inflammation model. One of these molecules, compound 20, demonstrated that a leukotriene antagonist pharmacophore can be modified such that it contains both antagonist activity and 5-lipoxygenase inhibitory activity.

CiteXplore: 2502629

DOI: 10.1021/jm00128a027

Patent ID: ┄