Gerspacher, Marc, Imbach-Weese, Patricia, Mah, Robert, Caravatti, Giorgio, Furet, Pascal, Fritsch, Christine, Schnell, Christian, Blanz, Joachim, Blasco, Francesca, Desrayaud, Sandrine, Guthy, Daniel Alexander, Knapp, Mark, Arz, Dorothee, Wirth, Jasmin, Roehn-Carnemolla, Esther and Luu, Van Huy (2015) Identification and optimisation of 4,5-dihydrobenzo[1,2-d:3,4-d]bisthiazole and 4,5-dihydrothiazolo[4,5-h]quinazoline series of selective phosphatidylinositol-3 kinase alpha inhibitors. Bioorganic and Medicinal Chemistry Letters, 25. pp. 3575-3581. ISSN 0960-894X

Abstract

Abstract: A cyclisation within a 4',5-bisthiazole (S)-proline-amide-urea series of selective PI3Kα inhibitors led to a novel 4,5-dihydrobenzo[1,2-d:3,4-d]bisthiazole tricyclic sub-series. The synthesis and optimisation of this 4,5-dihydrobenzo[1,2-d:3,4-d]bisthiazole sub-series and the expansion to a related tricyclic 4,5-dihydrothiazolo[4,5-h]quinazoline sub-series are described. From this work analogues inclusing 11, 12, 19 and 23 were identified as potent and selective PI3Kα inhibitor in vivo tool compounds.

Item Type:	Article
Keywords:	Oncology, kinase inhibitor, phosphatidylinositol-3-kinase-alpha
Date Deposited:	13 Oct 2015 13:11
Last Modified:	13 Oct 2015 13:11
URI:	https://oak.novartis.com/id/eprint/25254