Synthesis, structure–activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors

…, V Lucchini, C Gambacorti-Passerini

Index: Mologni, Luca; Rostagno, Roberta; Brussolo, Stefania; Knowles, Phillip P.; Kjaer, Svend; Murray-Rust, Judith; Rosso, Enrico; Zambon, Alfonso; Scapozza, Leonardo; McDonald, Neil Q.; Lucchini, Vittorio; Gambacorti-Passerini, Carlo Bioorganic and Medicinal Chemistry, 2010 , vol. 18, # 4 p. 1482 - 1496

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Citation Number: 44

Abstract

The synthesis, structure–activity relationships (SAR) and structural data of a series of indolin- 2-one inhibitors of RET tyrosine kinase are described. These compounds were designed to explore the available space around the indolinone scaffold within RET active site. Several substitutions at different positions were tested and biochemical data were used to draw a molecular model of steric and electrostatic interactions, which can be applied to design ...