Organic chemists from Colorado State University (CSU) have created a new powerful tool for drugs hunters or pharmaceutical chemists who discover new medicines. In a new study, published in the recent issue of journal Science, researchers demonstrated a simple and sophisticatedly designed chemical reaction that could open unexplored fields of chemistry with biological relevance for drug discovery.
As reported in the journal, their contribution is a major breakthrough for the new drug discovery. Assistant Professors Andrew McNally and Robert Paton, a synthetic chemist and the one who specialized in computational chemical design respectively, collaborated to develop a new reaction for carbon-carbon bond that defines the making and discovery of small-molecule drugs.
Instead of transition metal, the new reaction uses phosphorus to bind together molecular rings that are known as pyridines. The scarcity of accessible chemical reaction for stitching pyridine rings had been one of the major challenges in drug discovery.
The researchers explained that the newly created reaction is analogous to a common cross-coupling reaction that uses transition metal palladium as a catalyst to make carbon-carbon bonds. Palladium-catalyzed reactions have been adopted for over three decades in pharmaceutical labs as the key reactions for linking benzene rings.
Benzene coupling is a basic reaction in several pharmaceutically active chemicals which was used in synthesis of a large amount of drugs available today including anti-malarials, painkillers, and contraceptives. Late chemist John Stille from CSU was the major innovator of this reaction in the 1970s and 80s.
However, the palladium-catalyzed reaction is not well applicable for coupling pyridine rings. Coupled molecular rings of pyridine are important pharmacophore or a part of chemical that allows interaction with biological system – the fundamental to interaction between the drug and the body.
The new reaction will allow easy construction of chemical compounds called biological targets which was traditionally difficult to create. According to the researchers, it is also potential for discovery of drugs for old as well as new diseases. McNally said that the lab will always be for anyone in pharmaceutical setting and they can pick up the new reaction to discover any drug leads. Joining forces with Paton’s lab was important to findings of the new reaction, he added.
The research team had validated the use of phosphorus and tracked the mechanism by which challenging coupling of pyridine rings was arranged. They believed that it is the first study to a complete understanding on the making of these bonds.