Biologically oriented organic sulfur chemistry. 14. Antiinflammatory properties of some aryl sulfides, sulfoxides, and sulfones.

To extend earlier work, to examine the possibility that certain sulfoxides might serve as counterparts of amines in receptor-site interactions, and to add to the little information available about sulfoxides in medicinal chemistry, sulfoxides were prepared of the general structure XArS(O)C6H4(CHR)nCO2H, together with the sulfides and some of the sulfones. The products were evaluated as antiinflammatory agents by carrageenan-edema inhibition and uv-erythema inhibition. Four of the compounds had activity roughly comparable to aspirin or phenylbutazone in one or the other of these assays (2a-c, 3b). Sulfoxides did not seem especially promising as a class and usually were less active than the corresponding sulfides. The two most interesting compounds in these assays, o-(phenylthio)phenylacetic acid (2b) and its sulfoxide 3b, had no significant activity in adjuvant arthritis. Hydrogen-bonding effects are indicated in certain of the acids by their absence in the corresponding esters.