1 / 12

Atrasentan

Atrasentan. Route Selection by Craig Harris. Objective. To prepare 10 g+ of optically pure Atrasentan to gauge the activity of in-house endothelial antagonists in our tumour models before December 2001.

keene
Download Presentation

Atrasentan

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Atrasentan Route Selection by Craig Harris

  2. Objective • To prepare 10 g+ of optically pureAtrasentan to gauge the activity of in-house endothelial antagonists in our tumour models before December 2001. • Consequence: AZ’s competitor goes into development / dumped and potential licensing agreement with Yamanouchi Pharmaceuticals.

  3. Route Selection • Three publications; official process not registered (still in Phase II) • Abbott’s Asymmetric Route; rather long winded • Abbott’s Racemic Route; much more suited to scale up • Paris Asymmetric Route; large induction much more ameniable to large scale • Why not run both in a staggered fashion?

  4. Abbott’s Asymmetric

  5. Abbott’s Racemic

  6. Abbott Racemic Cont.

  7. Paris Asymmetric

  8. Conclusions • Paris asymmetric route easily best on paper; in practise overall yield was poor (10% chemical yield, 99% e.e.) but can be improved • Paris route provided a very quick way to control Abbott’s Racemic Route ran in parallel (14% chemical yield, 99% e.e.) • Target: Start, 04/08/2001; first submission, 06/09/2001

  9. Combien ça aurait couté?????? • An external reputable contract synthesis; official figure not available but we estimate for 10 g at 100% strength • 1,000,000 FF!!!! • et en Euros? = 152,671

  10. M. Pfau (Paris 5) G. Revial (Paris 5) P. Boutron M. Maudet P. Siret J-C. Arnould G. Pasquet G. Bird C. Delvare D. Dorison T. Boyle (U.K.) D. Roberts (U.K.) Acknowledgements

  11. Grob Pyrrole Formation

  12. Diastereofacial selectivity

More Related