Brannigan L H, Hodge R B, Field L
J Med Chem. 1976 Jun;19(6):798-802. doi: 10.1021/jm00228a012.
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.
为扩展早期的研究工作，考察某些亚砜在受体部位相互作用中可能作为胺的对应物的可能性，并补充药物化学中关于亚砜的少量现有信息，制备了具有通式XArS(O)C6H4(CHR)nCO2H的亚砜，以及硫化物和一些砜。通过角叉菜胶水肿抑制和紫外线红斑抑制试验，对这些产物作为抗炎剂进行了评估。在这些试验中的一项或另一项中，四种化合物的活性大致与阿司匹林或保泰松相当（2a - c，3b）。作为一类化合物，亚砜似乎没有特别大的前景，并且通常比相应的硫化物活性更低。在这些试验中，两种最有趣的化合物，邻（苯硫基）苯乙酸（2b）及其亚砜3b，在佐剂性关节炎中没有显著活性。某些酸中存在氢键效应，而相应的酯中则不存在，这表明了氢键效应的存在。
