Exselent collaboration

Wednesday, 9 December 2015

EXSELENT public/private collaboration produces great chemistry, delivering new catalysts and technologies to develop better medicines 

For almost 10 years now, scientists from AstraZeneca and the University of Stockholm have been working closely together in the laboratory, making great chemistry together.

The challenge? To impact the design and synthesis of new medicines by developing more effective chemical catalysts that give access to greener and more efficient processes. Furthermore we want to target and activate chemical bonds previously considered to be relatively inert and hence open up new chemical ways to make future drugs

The result? The collaboration, part of Sweden’s EXSELENT program, has delivered solid successes for all the partners. For AstraZeneca, it has given Medicinal Chemists access to cutting edge research and top researchers, and has helped advance the company’s scientific leadership in catalysis in organic synthesis.  For the University, it has given academics the chance to perform research with industry applications, and to test and understand the real impact and value of their innovations. For the Swedish government, it has enriched the research community and helped Sweden maintain its leadership position in the knowledge economy.

At AstraZeneca, we are particularly excited that the new catalysts from this collaboration appear to outperform earlier ones reported in literature. Active Pharmaceutical Ingredients (API) should not contain any traces of metals, however this is hard to achieve when using homogeneous catalysis. Within the EXSELENT collaboration, we have developed catalysts based on palladium, iron and iridium that have been incorporated into different porous materials, such as siliceous mesocellular foam (MCF) and metal organic frameworks (MOF). These catalysts show very low leaching. In addition, they show very good activity – meaning that only small amounts are needed to perform the catalytic reaction, something that makes our processes more efficient and environmentally friendly. In 2015 we have focused on two new topics, flow-chemistry and activation of C-H bonds. Flow technology will allow us to use the immobilized catalysts in a more efficient process friendly way. C-H activation (mimicking the reaction done by the liver metabolizing enzymes P450´s) will give us the possibility to functionalize drug-like molecules at a late stage (LSF) and make derivatives of our most advanced molecules in a more strategic way, and in addition protect metabolic “soft spots” or even make metabolites for evaluation in our clinical programs.

We are also very pleased that we have been able to recruit young scientists from this program. Another important measure of success for us is the number of peer-reviewed scientific publications that have come out of this collaboration. Since April 2014, we have four high quality publications with AstraZeneca authors and more in the works. (See links below).

As we head into EXSELENT’s 10th year, and to another round of proposals for funding in 2016, it is worth highlighting the hard work and dedication of all the people involved in the programme from academia, industry and government. The Medicinal Chemistry Departments in AstraZeneca’s Respiratory, Inflammation and Auto-immunity, and Cardiovascular and Metabolic Diseases Innovative Medicines units organised a celebration of the EXSELENT collaboration in Mölndal on November 25. Researchers from Stockholm University presented the latest research progress with the focus on novel porous materials with applications in catalysis and late stage functionalisation.

EXSELENT 

The EXSELENT programme started in 2006 with Stockholm University and the Department of Materials and Environmental Chemistry and the Department of Organic chemistry as the coordinators. The programme is jointly funded by VINNOVA (Sweden’s Innovation Agency) and the Swedish Science Council, and is one of the “Berzelii Centers”. AstraZeneca has been the main drug discovery partner since the outset, initially sponsored from the Södertälje research site but has for the last years been taken up by the Medicinal Chemistry community in Gothenburg.  

The founding strength of EXSELENT is the university’s chemistry research and ground-breaking application of materials chemistry in drug discovery. For the drug discovery part which AZ so far has been involved in the focus is and has been on catalysis in organic synthesis. This has been achieved in 3 ways: to find new synthetic routes to new compounds that were not possible previously; to utilize better and more effective routes through the Medicinal Chemistry exploratory phase; to have access to better catalytical methods in scale up and production ( less impurities, better Cost of Goods economy).

Publications resulting from the EXSELENT collaboration:

  1. ChemSusChem 2015, 8, 123 – 130
  2. Angew. Chem. Int. Ed. 2015, 54, 14094 –14098
  3. J. Org. Chem. 2014, 79, 3946−3954
  4. Chem. Eur. J. 2015, 21, 1 – 10 (VIP paper)
  5.  ChemViews Magazine – hot topics, review of article 4