A new way to replace carbon with nitrogen atoms could lead to better medicines

Key Points:

• Researchers at the University of Chicago have developed a new, gentler method for replacing carbon atoms with nitrogen atoms in drug molecules, overcoming limitations of older skeletal editing techniques that required harsh chemicals or were molecule-specific.
• Their process involves using blue light, oxygen, and a reagent called tetramethylthiourea to open and rearrange ring-shaped molecules, followed by a chemical step that seals the ring with the nitrogen atom in place, turning a previously problematic reaction state into a useful step.
• The team successfully applied this method to dozens of pharmaceutical compounds, including dronedarone, vinpocetine, yohimbine, and catharanthine, demonstrating its versatility and effectiveness.
• Early tests showed that a nitrogen-substituted version of vinpocetine had improved solubility, better metabolic properties, and reduced impact on a key heart protein, potentially lowering risks of heart rhythm issues.
• While not yet used in commercial drug manufacturing, the researchers believe this technique will become a valuable tool in medicinal chemistry for developing improved drug compounds.