Inhibitors of leukotriene B4. Synthesis and SAR of new β-enaminoester open-chain analogues of Zeneca ZD2138

Article abstract of DOI:10.1016/0960-894X(96)00058-3

A series of methoxy tetrahydropyranyl β-enaminoester has been discovered as inhibitors of LTB₄ production. These are unusual open chain analogues of Zeneca ZD2138, the highly potent orally active 5-LO inhibitor under development for the treatment of asthma and rheumatoid arthritis. In vitro, compound 1a inhibited LTB₄ formation in human whole blood with an IC₅₀ of 0.04 μM. In inflamed exudate in the rat 1a inhibited formation of LTB₄ with an oral ED₅₀ 3h after dosing of 3.0 mg/kg.