Synthesis and properties of symmetrical diurea based on propionic acid derivatives - potential multi-target inhibitors of sEH and COX-2

In our previous work, we described the production of isocyanates in high yields from non-steroidal anti-inflammatory drugs (NSAIDs) from the propionic acid group (naproxen, ketoprofen and flurbiprofen), as well as 1,3-disubstituted ureas based on them. As a continuation of our work, the resulting NSAID-based isocyanates were reacted with hexamethylenediamine (HMDA), yielding a series of symmetrical 1,3-disubstituted diureas in 56-84% yields. The resulting symmetrical 1,3-disubstituted diureas are potential multitargeted inhibitors of soluble epoxide hydrolase (sEH) and cyclooxygenase (COX).