NSERC grant could lead to more sustainable drug discovery, development

Organic chemistry is at the centre of a new $440,000 Natural Sciences & Engineering Research Council of Canada (NSERC) Collaborative Research and Development (CRD) Grant led by York chemistry Professor Art Orellana of the Faculty of Science. This collaborative research with F. Hoffmann-La Roche could result in an increase in the number of small molecule drug candidates in the next few years.

That is because Orellana’s team has developed a conceptually new, gentler approach to making pyridines, which are small molecules widely used in drug discovery and development.

Arturo Orellana

“For a number of years now, the mentality in our research group has been that we are going to target hard synthetic challenges that are actually going to provide solutions to real-world problems,” said Orellana.

The synthesis of complex heterocyclic molecules is an integral part of drug development and manufacturing. Pyridine, an aromatic organic compound with one nitrogen atom, is the most widely used heterocycle in FDA-approved drugs and its derivatives are in high demand. The problem is that current methods to create pyridine derivatives are so harsh they are not widely used. The development of new reactions will facilitate large-scale manufacturing of drug molecules, reduce costs and environmental impact, and could lead to a greater availability of new drugs.

“We have devised a conceptually new approach to make pyridine derivatives using exceptionally mild conditions that tolerate a wide range of functional groups,” said Orellana. “These reactions also provide immediate access to small molecules that possess ‘drug-like’ qualities and that are hard to make by other means. Our approach to these molecules can generate new structures to explore as drug leads.”

This is of particular interest to Roche, the largest biotech company in the world for sustainable drug manufacturing. The current CRD Grant leverages Roche’s $241,000 investment in Orellana’s fundamental research in synthetic organic chemistry.

“At Roche Small Molecule Technical Development, we develop the synthetic routes to bring our global pipeline of candidate molecules through clinical studies and to commercial production,” said Dan Fishlock, a principal scientist in process chemistry and catalysis at F. Hoffmann-La Roche in Basel, Switzerland. “Powerful new methodologies, such as those developed in the Orellana group, contribute to the organic chemistry scientific community and give us the tools that we need to bring innovative new drugs to patients around the world.”

Through their collaborative research project, “Cross-Coupling Reactions Leading to Chiral Heterocyclic Scaffolds for Drug Development and Manufacturing,” Orellana and the process chemistry and catalysis group at Roche will work on perfecting these new methods. In addition, once developed, these methods will be broadly applicable to the pharmaceutical sector in Canada and around the world.

“I am quite gratified to have been invited to apply for this internal grant program by the process chemistry group at Roche,” said Orellana. “This tells me that the work we are doing is meaningful. There is no better indicator of this than receiving this kind of support from a major player in the pharmaceutical sector.”

The collaboration and CRD Grant will also have training benefits for current and future graduate students in organic synthesis and problem solving related to drug development and manufacturing at York and with Roche. Already, one of Orellana’s students travelled to Roche global headquarters in Basel to present the group’s work to date.

“Visiting the Roche campus in Basel was an amazing learning experience for both my current work and future as a chemist. Presenting my work as well as listening to the work being done in other collaborative projects really highlighted how meaningful our work can be in the pharmaceutical industry,” said Isabelle Hunter, a first-year graduate student.

“When touring the campus and different divisions of the company, it was interesting to see how the molecules and methodology that we are working on can be taken and used in building larger compounds. Seeing the different aspects of what the company does, including the scale-up process, gave me a taste of what working in a pharmaceutical company would be like.”

In addition, Nour Wasfy, a second-year graduate student in the group, recently presented the group’s work in this area at the Canadian Society Chemistry Conference in Quebec City and earned an oral presentation award.

“We are very grateful for the support of fundamental organic chemistry research at York by Roche and NSERC,” said Orellana. “This will help elevate our research capacity and profile, and will benefit many students as well.”

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