Curse or Cure? A Perspective on the Developability of Aldehydes as Active Pharmaceutical Ingredients

There is a dichotomy between the increasing utility of aldehydes as tool molecules that bind to "undruggable" protein sites and the designation of the aldehyde functional group as a structural alert by the medicinal chemistry community. Herein we compile information about pharmacologically active aldehydes that are being used in humans. We summarize the learnings from these data, discuss advantages and challenges associated with aldehydes, and derive strategies for the successful development of aldehydes within drug discovery programs.