Research Initiative May Result in Decreased Drug Costs

Chemists from Rice University, University of Texas Southwestern Medical Center, and Brigham Young University have created a 1-step process for creating nitrogen-laden molecular precursors important for drug manufacturing.

This process will also cut the cost of creating nitrogen-containing functional groups for pharmaceuticals, according to a press release from Rice University. The design of functional materials and bioactive natural products, agrochemicals, should also be simplified due to the process.

The novel method involves creating free amines, which are compounds that have 1 or more nitrogen atoms. A type of amine, aromatic amines, are very prevalent, and are in more than one-third of drug candidates.

“Nitrogen atoms give polarity to the molecules,” said researcher László Kürti, PhD, synthetic chemist at Rice University. “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.”

Many researchers have pursued this goal, but none have been successful until the current team.

“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),” Dr Kürti said. “But the free aromatic amine products readily bind to these metal catalysts and can essentially poison the process.”

A transition metal catalyst (a dirhodium complex) is still used in the novel process, since it can effectively catalyze the introduction of unprotected alkylamino groups into aromatic rings, according to the press release. Previously, the most efficient processes require at least 3 steps to prepare free aromatic amines for use in drugs and bioactive materials.

“When you do things in multiple steps, you lose material with each step,” Dr Kürti said. “With our process, you gain not only speed but also efficiency and high material throughput, because you’re going to have the desired compound in just one step.”

Streamlining the process may be extremely beneficial to pharmaceutical manufacturers who may no longer have to go through long and complicated processes.

“Anybody who is interested in streamlining the synthesis of complex compounds that contain nitrogen now has a 1-step, 1-flask process,” Dr Kürti said. “Agrochemical companies, drug-discovery companies and anybody who makes fine chemicals will find this a very interesting tool.”

The new process also may decrease manufacturing costs that could, in turn, decrease drug costs, which has been a growing worry of many Americans.

“Anything you can do that expedites the introduction of nitrogen in these molecules and reduces the cost of production is going to be beneficial for drug development and for reducing the cost of drugs,” said researcher John Falck, PhD, the Robert A. Welch Distinguished Chair in Chemistry at the University of Texas Southwestern Medical Center. “Up to now, chemists have had to rely on circuitous routes to be able to introduce these nitrogens. And we’ve achieved access directly in a much more efficient process than the alternatives.”