Design and synthesis of boron-containing PDE4 inhibitors using soft-drug strategy for potential dermatologic anti-inflammatory application

PDE4 inhibitors are a validated approach as anti-inflammatory agents but are limited by systemic side effects including emesis. We report a soft-drug strategy incorporating a carboxylic ester group into boron-containing PDE4 inhibitors leading to the discovery of a series of benzoxaborole compounds with good potency (for example IC50 = 47 nM of compound 2) and low emetic activity. These compounds are intended for dermatological use further limiting possible systemic side effects.

Graphical abstractA carboxylic ester group is incorporated into boron-containing PDE4 inhibitors leading to the discovery of benzoxaborole carboxylic ester compounds with good potency against PDE4 and low emetic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide