3,3'-Di(1,3-triazolidine-4-one) system. V. Synthesis and pharmacological properties of 3,3' (1,2-ethanediyl)bis-(2-heteroaryl-1,3-thiazolidine-4-one) derivatives

Article abstract of DOI:10.1016/0223-5234(90)90181-2

A class of anti-inflammatory, analgesic and histamine H₁- and H₂-receptor antagonists the 2,2'-dihetero-arylbisthiazolidinones and their 1,1'-disulfones, obtained as [RR, SS] and [RS, SR] isomers, is described. The heteroaryl substitution at 2 and 2' carbons generally improves the pharmacological activities with respect to those of the previously studied 2,2'-diaryl analogues. In particular the 2,2'-dithienyl derivatives exhibit analgesic properties and, as [RS, SR] isomers 6b, 11b, 12b H₂-histamine receptor antagonism as well. The most effective acute anti-inflammatory agents appear to be the 2,2'-di(3-pyridyl) compounds 8a, 8b, 14a, 14b which also display analgesic activity. Moreover, an H₁-histamine receptor antagonism is almost selectively exerted by the 2,2'-di(2-pyridyl) derivatives 7a, 7b, 13a, 13b. The relationships between the assessed activities and the chirality and/or the sulfur oxidation state of the molecules are discussed. The anti-cancer potential was also evaluated against P 388 murine lymphocytic leukemia; however, the results were not significant.