Novel and selective spiroindoline-based inhibitors of Sky kinase

…, D Sheehan, JE Edmunds, A Delaney, Y Wang…

Index: Powell, Noel A.; Kohrt, Jeffrey T.; Filipski, Kevin J.; Kaufman, Michael; Sheehan, Derek; Edmunds, Jeremy E.; Delaney, Amy; Wang, Yuli; Bourbonais, Francis; Lee, Doh-Yeel; Schwende, Frank; Sun, Fang; McConnell, Pat; Catana, Cornel; Chen, Huifen; Ohren, Jeff; Perrin, Lisa A. Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 1 p. 190 - 193

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Citation Number: 14

Abstract

We report the discovery of a novel series of spiroindoline-based inhibitors of Sky kinase that bind in the ATP-binding site and exhibit high levels of kinome selectivity through filling the Ala571-subpocket. These inhibitors exhibit moderate oral bioavailability in the rat due to low absorption across the gut wall.

A convenient route to spiropyrrolidinyl-oxindole alkaloids via C-3 substituted ene-pyrrolidine carbamate radical cyclization