Periodic Reporting for period 1 - AiRPaDD (Advancing Reaction Platforms for Drug Discovery)
Période du rapport: 2023-02-01 au 2025-01-31
The AiRPaDD consortium comprises two academic (UPV/EHU and USFD) and two industrial (Sanofi and AZ) research groups, all of them working in the field of organic chemistry, which is the branch of chemistry that studies the synthesis and transformation of organic molecules. It is important because it helps us understand and create the molecules that make up everything in living organisms and also in our daily lives, from the food we eat to the materials and medicines we use. In the case of AiRPaDD, we work in organic chemistry from different approaches, both experimental and theoretical, with the goal of modifying molecules. Our work spans both basic science, aimed at discovering new reactions, as well as its more applied aspect, which focuses on potential applications in the development of new drugs. We also study these reactions and molecules from a theoretical perspective.
In the AiRPaDD project, four doctoral candidates are benefiting from a unique training programme to become highly skilled professional researchers in organc synthesis and drug discovery. More specifically, their research projects focus on developing new methods for creating and modifying existing chemical compounds that can be used in medicines. Organic and medicinal chemistry play a crucial role in this process by helping us design and synthesize molecules with specific properties that can improve the effectiveness of drugs. In general, the modification of the structure of certain molecules can help create species with new properties, improving or modifying their activity or reducing their toxicity and side effects.
Through innovative approaches, we aim to enhance the safety and performance of medicines, making them more effective at treating diseases while minimizing side effects. The close collaboration between academia and pharmaceutical companies helps bridge the gap between academic research and industry needs, working together to create new and better treatments for patients. Our work represents the intersection of scientific discovery and real-world applications, where research in the lab can lead to tangible benefits in medicine.
In the AiRPaDD project, four doctoral candidates are benefiting from a unique training programme to become highly skilled professional researchers in organc synthesis and drug discovery. More specifically, their research projects focus on developing new methods for creating and modifying existing chemical compounds that can be used in medicines. Organic and medicinal chemistry play a crucial role in this process by helping us design and synthesize molecules with specific properties that can improve the effectiveness of drugs. In general, the modification of the structure of certain molecules can help create species with new properties, improving or modifying their activity or reducing their toxicity and side effects.
Through innovative approaches, we aim to enhance the safety and performance of medicines, making them more effective at treating diseases while minimizing side effects. The close collaboration between academia and pharmaceutical companies helps bridge the gap between academic research and industry needs, working together to create new and better treatments for patients. Our work represents the intersection of scientific discovery and real-world applications, where research in the lab can lead to tangible benefits in medicine.
In the general context of organic synthesis and medicinal chemistry, we are working on four different research projects:
For example, we are particularly interested in the preparation and modification of heterocycles, a type of molecule consisting of rigid, cyclic structures that contain atoms other than carbon and hydrogen, especially nitrogen. Most of the commercial drugs used every day belong to this type of compound—heterocycles. For this reason, some of our efforts are directed towards their preparation, in some cases starting from the addition of two acyclic structures. In this project, the main reaction is the fusion of two of these molecules to form a new heterocyclic molecule, called pyrazole. We have already found experimental conditions to perform this reaction efficiently.
On the other hand, a second individual project aims at modifying these pyrazole structures by creating new bonds and attaching new functional groups to them. In particular, we have developed a new trifluoromethylation reaction for the design and development of reaction conditions to add a trifluoromethyl group to the pyrazoles. These new entities can be of great interest in the design of new pharmaceutical compounds.
In parallel, another project focuses on modifying certain amino acids, which are key organic molecules found in every protein and many drugs. This is a very hot topic in modern organic chemistry. We have successfully added new functional groups using a new and modern method, which can be seen as an interesting modification of previously known procedures.
Finally, the synthesis and preparation of highly functionalized alkenes is the objective of our last project. Alkenes are special organic motifs that are generally more reactive than alkanes, allowing for richer reactivity and access to more complex molecules. In this case, we have been able to attach reactive functional groups and atoms to the alkenes, such as boron atoms and nitrogen-containing motifs. In this way, very versatile and reactive species can be created. The reactions developed for this purpose are also of great novelty and interest.
In general, by modifying all these structures, we can create new versions of existing drugs with different properties, such as enhanced effectiveness, reduced side effects, or even new ways to treat diseases.
In parallel to the doctoral candidates' research activities, AiRPaDD training programme is equipping researchers with a strong interdisciplinary skill set, combining advanced scientific knowledge with transferable skills that will be essential for their future careers.
For example, we are particularly interested in the preparation and modification of heterocycles, a type of molecule consisting of rigid, cyclic structures that contain atoms other than carbon and hydrogen, especially nitrogen. Most of the commercial drugs used every day belong to this type of compound—heterocycles. For this reason, some of our efforts are directed towards their preparation, in some cases starting from the addition of two acyclic structures. In this project, the main reaction is the fusion of two of these molecules to form a new heterocyclic molecule, called pyrazole. We have already found experimental conditions to perform this reaction efficiently.
On the other hand, a second individual project aims at modifying these pyrazole structures by creating new bonds and attaching new functional groups to them. In particular, we have developed a new trifluoromethylation reaction for the design and development of reaction conditions to add a trifluoromethyl group to the pyrazoles. These new entities can be of great interest in the design of new pharmaceutical compounds.
In parallel, another project focuses on modifying certain amino acids, which are key organic molecules found in every protein and many drugs. This is a very hot topic in modern organic chemistry. We have successfully added new functional groups using a new and modern method, which can be seen as an interesting modification of previously known procedures.
Finally, the synthesis and preparation of highly functionalized alkenes is the objective of our last project. Alkenes are special organic motifs that are generally more reactive than alkanes, allowing for richer reactivity and access to more complex molecules. In this case, we have been able to attach reactive functional groups and atoms to the alkenes, such as boron atoms and nitrogen-containing motifs. In this way, very versatile and reactive species can be created. The reactions developed for this purpose are also of great novelty and interest.
In general, by modifying all these structures, we can create new versions of existing drugs with different properties, such as enhanced effectiveness, reduced side effects, or even new ways to treat diseases.
In parallel to the doctoral candidates' research activities, AiRPaDD training programme is equipping researchers with a strong interdisciplinary skill set, combining advanced scientific knowledge with transferable skills that will be essential for their future careers.
The main research achievements of AiRPaDD during the last months are related to the development of novel synthetic concepts that allow the preparation of small molecules of high scientific, pharmaceutical and societal value, like highly functionalized alkenes, pyrazole scaffolds and unsaturated amino acids. The common feature that all synthesized compounds share is the presence of a high level of substitution patterns, including functional groups that can serve as versatile platforms towards more complex molecules.
Thus, complexity, modularity and rapid assembly of useful functional groups are the key elements of our synthetic approaches.
These methodologies go beyond the state of the art in drug discovery. We are also applying cutting-edge technologies and experimental chemistry to prepare a number of substrates.
We are also using modern computational technologies to advance in the understanding of radical reactivity, and in the complex mechanisms of the reactions we are developing experimentally.
Thus, complexity, modularity and rapid assembly of useful functional groups are the key elements of our synthetic approaches.
These methodologies go beyond the state of the art in drug discovery. We are also applying cutting-edge technologies and experimental chemistry to prepare a number of substrates.
We are also using modern computational technologies to advance in the understanding of radical reactivity, and in the complex mechanisms of the reactions we are developing experimentally.