A major step towards simpler drug development has been taken at the University of Gothenburg. In a new study, researchers have developed stable boron-fluorine compounds that make it possible to increase the effect or reduce side effects without breaking down the medicine.
Chemical compounds based on the element boron are central tools in modern chemistry and are used, among other things, to build drugs, advanced materials, and molecules for medical diagnostics. Some types of boron compounds are still difficult to produce, especially when the boron atom must be placed very precisely in a complex molecule. This limits the possibilities for further developing existing drugs and bioactive substances.
No time-consuming purification
"In our study, we have developed a new class of stable and easy-to-use boron compounds, known as BF₂-boracycles. These can be produced in a simple, metal-free, and scalable way without time-consuming purification steps. The compounds are also unusually stable but at the same time highly reactive when used in chemical reactions, says Henrik Sundén, professor of organic chemistry at the University of Gothenburg.
The big advantage of BF₂-boracycles is that they make it possible to modify complex molecules at a late stage. This means that you can take a finished drug or a biologically active substance and, in a controlled way, build on new functions to improve its effect or reduce side effects.
Compared to existing methods, the new method involves fewer process steps when designing drugs, less waste, and significantly better resource efficiency, which also makes it more environmentally friendly. The method has been developed in collaboration with the University of Caen, France, and the University of Ljubljana, Slovenia.
No need to break down the drug
The researchers replace a hydrogen atom in the drug molecule with the newly developed boron compound in a chemical process. This opens the door to replacing the boron compound in the next step with a molecule that can give the drug new and better properties. Previously, drug developers have been forced to incorporate the new molecule into the original drug during its construction, as it is not possible to replace the hydrogen atom directly with a functional molecule.
"Our discovery means that you don't have to take the drug apart to improve it. Instead, you can test perhaps a hundred different functional molecules that easily replace the boron compound to see which molecule best improves the drug," says Henrik Sundén.
Useful for cancer diagnostics
The study shows that these boron compounds can replace many different types of chemical groups, including halogens, alcohols, and azides. It can also be used in important coupling reactions that often occur in medicinal chemistry. It is particularly interesting that the method also works for introducing radioactive iodine, which is crucial in the diagnosis and treatment of cancer.
In scintigraphy, radioactive iodine is introduced into the part of the body that is to be examined. A gamma camera that detects the radioactive uptake takes images from different angles. This allows doctors to detect pathological changes in the body at an early stage. In tumour diagnostics, scintigraphy is mainly used when metastasis in the skeleton is suspected, but also to examine the liver, kidneys, thyroid, and lymphatic system.
The development has been carried out in collaboration with AstraZeneca, where drug developers are interested in being able to fine-tune the function of drugs at a late stage to avoid having to start over from the beginning.
Scientific article in Angewandte Chemie: Stable BF2 Boracycles as Versatile Reagents for Selective Ortho C-H Functionalization
