Linked Aryl Aryloxypropanolamines as a new class of lipid catabolis agents

The synthesis of a series of stilbene, biaryl, tolane, diaryl ether, sulfide, sulfoxide, and sulfone oxypropanolamines as potential antiobesity agents is described. These compounds were evaluated in a mouse lipid catabolism screen, and the more active members of the series, 4, 57, and 58, were further investigated in rats and dogs. 1-(2,6-Ditert-butyl-4-trans-styrylphenoxy)-3-isopropylamino-2-propanol (4) possessed considerable lipid catabolic activity in mice and caused a significant reduction in the body weight of rats after 5 weeks and of dogs after 6 weeks. Only hematological irregularities in a chronic toxicity study precluded further development of this compound as an alternative antiobesity treatment.