One activation method that opens up a great many possibilities for different functional groups, at least on paper, is borylation. In this process, a chemical group containing the element boron is bonded to a carbon atom in the scaffold. The boron group can then simply be replaced by a whole range of medically effective groups.

"Although borylation has great potential, the reaction is difficult to control in the lab. That's why our comprehensive search of the worldwide literature only turned up just over 1,700 scientific papers on the subject," Atz says, describing the starting point for his work.

The idea was to take the reactions described in the scientific literature and use them to train an AI model, which the research team could then use to consider new molecules and identify as many sites as possible on them where borylation would be feasible. However, the researchers ultimately fed their model only a fraction of the literature they found. To ensure that the model wasn't misled by false results from careless research, the team limited itself to 38 particularly trustworthy papers. These described a total of 1,380 borylation reactions.

To expand the training dataset, the team supplemented the literature results with evaluations of 1,000 reactions carried out in the automated laboratory operated by Roche's medicinal chemistry research department. This allows many chemical reactions to be carried out at the milligram scale and analysed simultaneously. "Combining laboratory automation with AI has enormous potential to greatly increase efficiency in chemical synthesis and improve sustainability at the same time," says David Nippa, a doctoral student from Roche who accomplished the project together with Atz.

The predictive capabilities of the model generated from this data pool were verified using six known drug molecules. In five out of six cases, experimental testing in the laboratory confirmed the predicted additional sites. The model was just as reliable when it came to identifying sites on the scaffold where activation isn't possible. What's more, it determined the optimum conditions for the activation reactions.

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Artificial intelligence finds ways to develop new drugs - Mirage News