Discovery of a novel tricyclic 4H-thiazolo[5',4':4,5]pyrano[2,3-c]pyridine-2-amino scaffold and its application in a PI3Kα inhibitor with high PI3K isoform selectivity and potent cellular activity

  • Bioorg Med Chem Lett. 2015 Sep 1;25(17):3582-4. doi: 10.1016/j.bmcl.2015.06.077.
Marc Gerspacher  1 ,  Robin A Fairhurst  2 ,  Robert Mah  2 ,  Esther Roehn-Carnemolla  2 ,  Pascal Furet  2 ,  Christine Fritsch  2 ,  Daniel A Guthy  2
Affiliations
  • 1. Novartis Institutes for BioMedical Research, Novartis Pharma AG, WKL-136.4.84, CH-4002 Basel, Switzerland. Electronic address: [email protected].
  • 2. Novartis Institutes for BioMedical Research, Novartis Pharma AG, WKL-136.4.84, CH-4002 Basel, Switzerland.
PMID: 26164189 DOI: 10.1016/j.bmcl.2015.06.077
Abstract

A novel, previously undescribed 4H-thiazolo[5',4':4,5]pyrano[2,3-c]pyridine tricyclic scaffold has been discovered. The application of this novel chemotype leading to a potent and selective prototype PI3Kα Inhibitor with favorable physicochemical and PK-properties is described.

Keywords
4H-Thiazolo[5′,4′:4,5]pyrano[2,3-c]pyridine-2-amino derivative; Oncology; Phosphatidylinositol-3-kinase (PI3K); Selective PI3Kα Inhibitor.