PROCESS DEVELOPMENT
Developing new methods for nucleoside synthesis
Peakdale Molecular is now firmly established as a leading provider of process development and medicinal chemistry services to the pharmaceutical industry and has grown rapidly over the past decade, mainly due to its ability to offer high-quality services in niche areas, including new chemistries for nucleoside pharmaceutical intermediates.
T
he well-documented upheaval in the pharmaceutical sector in the past ten years has been mirrored in the contract research sector, as small companies that supply the global market compete to keep up with the changing demands of Big Pharma.1 This period of change has coincided with the emergence of China and India as major players in the scientific services industry, adding an extra level of competition Western companies face in the current economic climate. Peakdale Molecular has evaluated the changing marketplace over this period and has had to adapt its offering significantly to keep ahead. It has done this by choosing to repeatedly climb the technology ladder, building expertise in areas of chemistry that are traditionally considered ‘difficult’. Peakdale’s success in becoming a leading supplier of
nucleoside research serves is one example of this strategy and the company’s early activities in this field are described here. More recently, Peakdale has been able to utilise its synthetic organic chemistry skills in industries other than drug discovery, for example in organic electronics.
Nucleosides as drug candidates Nucleosides are important drug candidates: they have been proven to be active against a range of cancers and viral infections such as HIV and herpes. Among the most famous of commercial successes are AZT, acyclovir and emtricitabine, illustrated in Figure 1. More recently, excitement surrounding the prospect of the development of an effective, easily administered and well-tolerated hepatitis-C treatment prompted Gilead’s $11 billion takeover of Pharmasset, a company
focused on developing nucleoside/tide analogues of viral polymerase inhibitors. Clearly, the synthesis of nucleosides and nucleotides, an achievement that won Lord (Alexander R.) Todd the Nobel Prize in chemistry in 1957, is as relevant today as ever. Peakdale’s first serious involvement with nucleosides came in 2002. At this time the company had recently moved from its beginnings in an industrial unit in Glossop, UK to a 3,750 sq m purpose-built facility in Chapel-en-le-Frith. The company employed about 30 chemists and had built a reputation for quality synthetic chemistry through custom synthesis projects and the development of its own catalogue business. Pfizer was one of the companies that utilised Peakdale’s strength in synthetic chemistry, and this was a key period for both businesses – Pfizer was planning to increase its outsourcing of early- stage drug discovery and Peakdale needed to grow to fill its new building which today houses about 85 chemists. Dr Phil Wainwright, who led the Peakdale
Peakdale has expertise in all areas of modern synthetic and medicinal chemistry from small-scale libraries through to a kilo-lab facility, an ADME lab and computational chemistry support. Peakdale can also offer expertise in the specialist areas of high-pressure reactions, microwave reactions, and nucleoside and alkaloid chemistry.
20 sp2 Inter-Active July/August 2012
FTE team that took on the challenge of providing Pfizer with a novel nucleoside library, describes the preparation that went into winning that first FTE project: “We initially had to go through an interview process. The team was very much advertised through their previous work experience, and Pfizer set us a series of targets for which to develop hypothetical routes. This was followed up by a teleconference and discussion over these findings. Nucleoside chemistry requires knowledge in a specific area, and I think they wanted to check out not only how much we knew, but also our enthusiasm and willingness to learn a new subject area. They must have been pleased with what they saw, as this led to Peakdale winning the contract, a three-year, six-chemist FTE on a nucleoside research project. We were fortunate in Pfizer providing us with the funding for one month
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