Nucleoside and nucleotide discovery
Nucleosides and Nucleotides receive extensive synthetic attention due to their numerous uses in therapeutic and biotechnology applications. Examples include Sofosbuvir1, an important antiviral medication for the treatment of the hepatitis C virus (HCV) which works as a selective inhibitor of HCV NS5B polymerase with a high barrier to viral resistance, and more recently Remdesivir2 for its potential use in the treatment of Covid-19. Concept Life Sciences has unrivaled expertise in the synthesis of nucleosides and nucleosides from route development to synthesis of mg to kg scale.
Capabilities and experience
Scientists at Concept Life Sciences have significant hands-on experience in the synthesis of nucleosides and nucleotides and have published or presented a wide variety of this work. Projects have included collaborations and partnerships relating to milligram scale discovery chemistry through to kilogram scale process development as well as GMP and RSM manufacture in order to support our clients’ drug discovery programmes. Our teams have extensive experience in the synthesis, purification and scale up of:
- Novel sugars and nucleosides
- Novel purine and pyrimidine derived bases
- Novel nucleotide monophosphates and triphosphates
- Novel nucleotide phosphoramidate and phosphate prodrugs
Synthesis, purification and characterization are achieved by:
- UPLC / ion exchange systems using methods specifically designed for nucleosides and nucleotides
- Fully automated normal and reverse phase Isolera chromatography systems
- ELS and mass-directed prep HPLC detectors for the purification of UV-inactive sugars
- Lyophilisation for convenient isolation of purified material
- Multinuclear NMR for stereochemistry determination experiments and structure elucidation
- State-of-the-art scale up facilities for route optimization and process development including 10-50L jacketed vessels, flow chemistry and fully compliant GMP and RSM manufacturing capabilities
Our project teams have a demonstrated track record of producing robust nucleoside and nucleotide candidates suitable for ‘proof-of-concept’ testing and have made key contributions to compounds undergoing clinical development. We have extensive experience in the complexities involved in the nucleotide prodrug strategies common to the marketed antivirals, Sofosbuvir2, Tenofovir disoproxil5 and Remdesivir3. Our long-established history of scaling up complex chemistry delivers increased yields, safety and process improvements and shorter time-frames resulting in more cost effective projects for our clients.
Our personalized approach is provided with complete confidentiality and is underpinned by clear and regular communication from a dedicated project team while ensuring complete protection of Intellectual Property.