Drastically simplifying the synthesis of future drugs: the successful goal of Charlou Rognan’s dissertation

Every drug has a specific molecular structure—a combination of atoms arranged precisely to interact with a target in the body. Their production is often a laborious process and requires numerous synthesis steps. This complex protocol is different for each drug, much like a LEGO building manual, allowing different structures to be built step by step, brick by brick.

Charlou Rognan devoted his dissertation to the development of new, rapid, and effective methods for synthesizing molecules with bioactive potential. First, the young researcher explains that certain structures are particularly common in many drugs: “New bioactive compounds are discovered every year, and analysis of these compounds reveals commonalities among many of these structures. Between 2013 and 2023, 82% of new drugs approved by the FDA (the U.S. agency responsible for drug regulation) contained one or more cyclic structures with at least one nitrogen (N) atom. These structures, known as nitrogen-containing heterocycles, exhibit a wide range of biological activities and are commonly found in many natural and synthetic molecules with known biological activities. The sulfur (S) atom is also of great interest. Present in 23% of drugs, sulfur makes the molecule more hydrophobic, meaning it can more easily cross the cell membrane. The majority of these sulfur-containing drugs also contain nitrogen, underscoring the importance of N- and S-containing heterocycles in the search for new bioactive compounds.” Based on this observation, Charlou Rognan decided to develop a sort of molecular “framework” containing sulfur- and nitrogen-containing chemical functional groups, ready to react in different ways to create new N,S-heterocycles: “It’s like a LEGO set that serves as a starting point for creating several different drugs. Imagine the ‘body’ of a LEGO animal, where all you’d have to do is clip on specific limbs to create a multitude of different animals. Here, it’s the same thing: this ‘framework’ contains certain key elements of a drug that we transform in different ways to obtain several molecules with bioactive potential.”

In 2024 and 2026, he published his^work¹⁻²and described innovative synthesis methods for this molecular scaffold: “Instead of carrying out several synthetic steps in sequence, I used a ‘domino’ reaction in which all the components of this sulfur-nitrogen framework assemble through a well-oiled cascade of reactions, without human intervention between each step. This allows for multiple transformations to be carried out at once, unlike conventional methods, which often require isolating each reaction intermediate before moving on to the next step.” It’s as if our LEGO set were capable of twisting and locking into novel positions to build objects far more complex than simple flat bricks. The researcher notes that the diversity of the structures tested is key in pharmaceutical research: “With this system, we increase the number of molecules to be tested using a single synthetic pathway, and, consequently, the probability that at least one will exhibit promising biological activity.”

In summary, this domino reaction transforms chemical synthesis into a simpler, more efficient, and more cost-effective process for building a basic building block. This basic building block is then used to synthesize several different sulfur- and nitrogen-containing heterocycles found in many drugs. These “ready-to-use” structures will save researchers time in designing the drugs of the future.