Chemists make key advancements to simplify drug design and production

labResearchers at Rice University, the University of Texas Southwestern Medical Center and Brigham Young University have discovered a one-step solution to make nitrogen-laden molecular precursors for the preparation of drugs and other bioactive molecules. Research announced this month in Science will simplify the process and cut the cost of creating key nitrogen-containing functional groups for pharmaceuticals, said László Kürti, a synthetic chemist at Rice who developed the technique along with his colleague at UTSWMC, John Falck.

The researchers also reported that the technique should also simplify the design of agrochemicals, functional materials and bioactive natural products.

The new method involves making free amines, compounds with one or more nitrogen atoms that are essential to metabolic processes. Aromatic amines, which incorporate stable molecular fragments called aromatic rings, are substructures in more than a third of drug candidates, Kürti said.

“Nitrogen atoms give polarity to the molecules,” Kürti said. “They also help bind to molecules like proteins and enzymes. That’s why you see an abundance of nitrogen atoms in biologically active compounds, especially in active pharmaceutical ingredients that are used in medicines; they need to interact with biological systems.”

“There is huge demand for making these aromatic amines quickly and efficiently, and for decades now, people have been trying to make them with catalysts that contain transition metals (often used to speed up chemical reactions),” he said. “But the free aromatic amine products readily bind to these metal catalysts and can essentially poison the process.”

A long-term goal of Kürti’s lab is to design simplified amination chemistry that circumvents the use of transition metals.

Although the new process still makes use of a transition metal catalyst, a dirhodium complex, that effectively catalyses the direct introduction of unprotected alkylamino groups into aromatic rings.


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