Drug Late-Stage Modification by Photocatalytic Conversion of a Carboxyl Group into a Heterocycle

Keywords

photoredox cyanation - heterocycle installation - late-stage modification - bioisostere replacement

Significance

Nicewicz and co-workers reported a straightforward photocatalytic method for converting drug molecules bearing a carboxyl group into their imidazole bioisosteres. The method was also applied to the synthesis of Flurbiprofen and Fenoprofen oxadiazolone and oxathiadiazolone analogues.

Comment

Replacement of a carboxyl group with its bioisosteres typically requires multistep procedures. Therefore, simple one-step methods, such as that reported by Nicewicz and co-workers, are highly valuable in medicinal chemistry. Their approach provides easy access to three types of bioisosteres directly from the parent drug molecule, greatly simplifying synthesis.