Sugar Modified Nucleosides and Nucleotides – The Synthesis of Anti-Viral Drugs

The development of antiviral drugs has been spurred by a major global health issue; the emergence of new viruses over the last 35 years. The number of people affected by these diseases is staggering, leading to the development of breakthrough antiviral drugs. According to the World Health Organisation, the HIV virus is estimated to have caused 36 million deaths and there are an estimated 35 million people currently living with AIDS. Hepatitus C Virus (HCV), first identified in 1989, is estimated to have infected almost 3% of the World’s population, that’s 150-200 million people.

The response of the pharmaceutical industry to these threats has been rapid. Breakthrough antiviral drugs, such as Tenofovir and Sofosbuvir, are transforming the prognosis for newly infected patients. These antiviral drugs would not exist if it wasn’t for the skill and ingenuity of medicinal and organic chemists in inventing methods for the synthesis of nucleoside analogues.

This webinar will feature two presentations: The first will be a review of some of the most important synthetic strategies that allow chemists to make key structural changes to the sugar-portion of nucleosides. The second presentation will showcase a recent medicinal chemistry program carried out by Peakdale Molecular in partnership with Idenix Pharmaceuticals. This program is focused on the development of experimental nucleoside analogues containing locked nucleic acids for the treatment of HCV and will highlight the problems nucleoside chemists face when working to develop new antiviral drugs.

Key Learning Objectives:

• Discussion and key references for the synthesis of sugar modified nucleosides, focusing on the 4’- and 2’-positions
• Discussion of the syntheses of the sugar portions of the antiviral drugs, Sofosbuvir and Tenofovir
• Presentation of a successful synthetic campaign to access conformationally locked nucleosides and nucleotides and a discussion of their activity against HCV NS5B polymerase

Speakers

Dr. Nigel Allanson, Group Leader, Peakdale Molecular

Dr Nigel Allanson obtained his PhD from Imperial College London in 1986 and has since worked in the UK and US Pharmaceutical industry. He has been a group leader at Peakdale Molecular Ltd for four years.

Message Presenter

Dr. Mark Betson, Group Leader, Peakdale Molecular

Dr Mark Betson obtained a 1st Class honours degree from the University of Manchester and then completed a PhD in Organic Chemistry at the University of Cambridge, studying under the supervision of Prof Ian Fleming. Following this he returned to Manchester to work as a Postdoctoral Research Associate with Prof Jonathan Clayden, working on the discovery of new atropisomeric compounds. Mark has been with Peakdale Molecular since 2004 and is currently a Group Leader with a special interest in nucleoside chemistry. As an active member of the SCI Young Chemist’s Panel, Mark has sat on the organising committee of several national research symposia and is also currently helping to organise the RSC’s up-coming conference, “Nucleosides and Nucleotides: Synthetic and Biological Chemistry”.

Message Presenter

Dr. Steve Moore, Lead Chemist, Peakdale Molecular

Dr Stephen Moore joined Peakdale Molecular in January 2008, where he is currently a Lead Chemist. During this time he has contributed successfully to a diverse range of client projects, specialising in emerging collaborations within the nucleoside/nucleotide field. Since 2011, Stephen has led a Peakdale team through a highly successful collaboration with a global leader in antiviral therapies, delivering novel anti-HCV compounds and scale up technology into the client’s programme. Stephen completed his MChem at the University of York in 2004, where he subsequently remained to com­plete a PhD in 2007, under the supervision of Professor Peter O’Brien.

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