Preparation of 3,5-diaryl-1,2,4-oxadiazoles and analogs as activators of caspases and inducers of apoptosis.

Abstract

A method of treating a disorder responsive to the induction of apoptosis comprises administration of title compds. [I; Ar1 = (substituted) aryl, heteroaryl; Ar3 = (substituted) aralkyl, aryloxy, phenoxymethyl, anilino, benzylamino, benzylideneamino, benzoylamino, Ar2; Ar2 = (substituted) aryl, heteroaryl; A, B, D = CR10, CR10R11, N, NR12, O, S; R10, R11 = H, (substituted) alkyl, cycloalkyl, aryl; R12 = H, (substituted) alkyl, cycloalkyl, aryl]. Thus, 3-chlorothiophene-2-carbonyl chloride and 4-chlorobenzamidoxime were refluxed 1 h in dioxane; BF3.Et2O was added followed by further reflux for 5 h to give 72% 3-(4-chlorophenyl)-5-(3-chlorothiophen-2-yl)-1,2,4-oxadiazole. This induced apoptosis in T-47D tumor cells with EC50 = 3614 nM. [on SciFinder(R)]