(Acylaryloxy)acetic acid diuretics. 1. (2-Alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids

Abstract

Discovery of (acryloylaryloxy)acetic acids as a new class of potent diuretics prompted investigation of related bicyclic compounds. Annelated analogues of the parent series, the (2-alkyl- and 2,2-dialkyl-1-oxo-5-indanyloxy)acetic acids, were studied. Those compounds, unlike the monocyclic parent compound, lacked the double bond adjacent to the carbonyl group. More importantly, they possessed saluretic and uricosuric properties [in rats, dogs and chimpanzees]. The optimal single 2-substituents for maximal saluretic and uricosuric activity were determined. In general, better activity was observed when a second 2-alkyl substituent (especially methyl) was present in the molecule. Replacement of the carboxy substituent by 5-tetrazolyl generally resulted in a reduction in activity.