Synthesis and biological evaluation of cyanoguanidine derivatives of loratadine

Cyanoguanidine derivatives of loratadine (3a-i) were synthesized and screened for antitumor and anti-inflammatory activity. The most promising compound 3c (R = n-C8H17) possessed at least twofold higher in vitro cytotoxicity than 5-fluorouracil against mammary (MCF-7 and MDA-MB 231) as well as colon (HT-29) carcinoma cells. The mode of action, however, is so far unclear. The participation of the COX-1/2 enzymes on the cytotoxicity, however, is very unlikely. Nevertheless all compounds showed stronger in vivo anti-inflammatory activity than ibuprofen in the xylene-induced ear swelling assay in mice.