Gleevec® (or Glivec®, STI571) is a new drug effective in the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumors (GIST) marketed by Novartis. It possesses a unique mode of action by the inhibition of the BCR-ABL tyrosine kinase, a key-player in the signalling cascade responsible for CML. Gleevec® is also an inhibitor of the receptors for platelet-derived growth factor (PDGF) and stem cell factor (SCF) which explains the drug's property to inhibit proliferation and to induce apoptosis in GIST cells. The drug was developed and approved in record time. The current production synthesis is very effective and robust but has some drawbacks in terms of throughput and potential mutagenicity of several intermediates. A new synthesis tackling these deficiencies was developed and scaled up. It turned out that a simple change in the order of assembling the molecule applying almost the same chemistry as the previous synthesis could avoid most of the aforementioned problems. This lecture summarizes the different phases of this Technical Live Cycle Project starting from brainstorming, basic screening, route selection and finally process development and scale-up of the new synthesis.
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Back to The 37th Middle Atlantic Regional Meeting (May 22-25, 2005)