Synthesis of Carboranyl Flurbiprofen and Its Biological Evaluation—An Example of Carborane Not as a Phenyl Ring Surrogate

ABSTRACT “Carborane replacing phenyl ring” strategy has been frequently applied in drug modification because of the similar hydrophobicity and size between carborane and a rotational phenyl ring. We replaced the terminal phenyl ring of an NSAID flurbiprofen with carborane and synthesized the carboranyl flurbiprofen successfully. The carboranyl flurbiprofen lost its inhibitory activity toward COX‐1 and COX‐2, suggesting that carborane could not always serve as a phenyl ring surrogate. The biodistribution of carboranyl flurbiprofen was measured using ICP‐MS, revealing a high uptake in the liver, kidney and pancreas. The brain/blood ratio was 0.27 at 5 h post‐injection, suggesting an enhanced blood‐brain barrier permeability.