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The Impact of Synthesis Innovation in Drug Discovery

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The term "process chemistry" describes the action of "scaling up" reactions  taking small quantities of a chemical compound and synthesizing it on a much greater scale. A process chemist is tasked with developing synthetic routes that are safe, cost-effective and efficient at a commercial scale.

We recently had the pleasure of speaking with Danica Rankic, Associate Principal Scientist, MSD to learn more about their process chemistry activities. She touches on the synthesis strategies impacting drug discovery and provides a snapshot of her upcoming talk, taking place at the 6th Winter Process Chemistry Conference in December.

Laura Lansdowne (LL): Can you tell me a little about your professional background and your drug discovery activities at MSD?

Danica Rankic (DR):
I received my Ph.D. in 2010 from the University of Calgary working with Prof. Brian A. Keay on ligand modification of BINAP for application in asymmetric catalysis. Then, I moved on to Princeton University to complete a post-doctoral fellowship with Prof. David W. C. MacMillan. This work cumulated in the enablement of direct β-arylation of ketones and aldehydes using photoredox catalysis. I subsequently joined Pfizer in 2013 where I worked until 2017 as a Principal Scientist and group lead directing synthesis teams on projects targeting Alzheimer’s, depression, pain and diabetes. In 2017, I joined the Discovery Process Chemistry group at MSD’s Boston site where I work with our discovery chemistry colleagues to identify and develop novel oncology therapeutics. My role in Discovery Process Chemistry is to develop innovative synthetic chemistry solutions to help teams rapidly assess structure-activity relationships (SAR) and leverage those solutions to streamline the delivery of new medicines to the clinic.

LL: What is process chemistry and how does it fit within the drug development pipeline?

Process chemistry is a discipline that impacts the drug development pipeline from supplying active pharmaceutical ingredients (APIs) for early clinical trials, to commercial manufacture of drug substance. Traditionally, the responsibility of the process chemist is to develop a safe, cost-effective, green and sustainable synthesis of drug substance. At MSD, process chemistry plays a broader role which spans both discovery and development – impacting the entire life cycle of a drug, from target validation to commercial route selection.

LL: Are there any synthesis strategies you could highlight that you feel have made a particular impact on drug discovery success?

The use of high throughput experimentation (HTE) has been incredibly enabling in the field of drug discovery. It allows a chemist to perform hundreds or thousands of miniature reactions in a short period of time. The data generated from these experiments can be used to identify unprecedented chemical reactions or to optimize yields and minimize side products for a key bond disconnection. HTE impacts the entire discovery pipeline from parallel medicinal chemistry efforts for establishing SAR to informing on chemistry required for the scale-up of key compounds for safety studies.

LL: You are speaking at the upcoming “6th Winter Process Chemistry Conference”, December 2019, could you tell us about the focus of your talk?

The focus of my talk is on the role of synthetic chemistry as a differentiating science in the discovery and progression of novel IDO1 inhibitors in a safe and sustainable manner. I will specifically address aspects of process safety in synthesis of oxadiazole fragments and the use of biocatalysis strategies for the benzocyclobutyl amine fragments present in our key compounds.

Danica Rankic was speaking with Laura Elizabeth Lansdowne, Science Writer for Technology Networks.