Synthesis and Structure-Activity Relationships of Antiallergic N-[4-[4-(1H-Indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamides Possessing Both Antihistaminic and Anti Slow-Reacting Substance (SRS) Activites

Abstract

A series of N-[4-[4-(1H-indol-3-yl)piperidinoalkyl]-2-thiazolyl]alkanamide derivatives were synthesized and tested for in vivo antianaphylactic activity and in vitro anti slow-reacting substance (SRS) activity. Among the compounds synthesized, N-[4-[4-(1H-indol-3-yl)piperidinomethyl]-2-thiazolyl]propanamide (7) was the best balanced compound (antianaphylactic activity, ED₅₀=0.92mg/kg p.o.; anti-SRS activity, IC₅₀=0.89μg/ml). Regarding the biological activities of 7, we ascribe the antianaphylactic activity to its potent antihistaminic activity and the anti SRS activity to the inhibition of 5-lipoxygenase.