Researchers have developed a family of reagents that can add tight, ring-shaped structures that boost a drug's beneficial properties to a wide variety of drug candidates. Critically, the synthesis of the ring structure significantly reduces the multiple steps required in previous methods, a barrier that has sometimes resulted in the discontinuation of drug development in the past. Ring structures are appealing additions to help optimize a drug's properties. For example they can help limit unwanted clearance of the drug from the body. The smallest ring structures, with just three or four carbon atoms, are difficult to synthesize. As well, finding a way to attach the ring to the pharmaceutical agent without "tangling" the molecules has proven to be challenging. Here, Ryan Gianatassio and colleagues were able to strategically add ring structures containing four atoms to a nitrogen site in many complex, drug-like molecules. A little like a mouse trap, the reagent "springs" open when it comes into contact with the pharmaceutical agent, effectively latching onto the ring. Importantly, the researchers' synthesis technique bypasses the multiple steps required in previous recipes for ring-like structures, which may help speed up the development process for numerous pharmaceuticals. The authors note that their new ring structure has already helped in the clinical setting, where in one case it enabled the pursuit of a pre-clinical pharmaceutical candidate that had previously been discarded because of inefficiencies in the synthesis.
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Science