Replacement of aromatic or heteroaromatic groups in nonsteroidal antiinflammatory agents with the ferrocene group

Ferrocene analogues of the antiinflammatory agents tolmetin (1), fenbufen (2), flurbiprofen (3), and fenclofenac (4) were synthesized and tested for biological activity. The derivatives exhibited little or no antiarthritic or platelet antiaggregatory activity, indicating that the ferrocene moiety is a poor bioisostere for aromatic or heteroaromatic groups in nonsteroidal antiinflammatory agents.