175205-25-1Relevant academic research and scientific papers
Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors
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
experimental part, p. 1482 - 1496 (2010/04/29)
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 more potent and selective RET inhibitors. The crystal structures of RET kinase domain in complex with three inhibitors were solved. All three compounds bound in the ATP pocket and formed two hydrogen bonds with the kinase hinge region. Crystallographic analysis confirmed predictions from molecular modelling and helped refine SAR results. These data provide important information for the development of indolinone inhibitors for the treatment of RET-driven cancers.
Quinoline-3-carbothioamides and related compounds as novel immunomodulating agents
Tojo, Takashi,Spears, Glen W,Tsuji, Kiyoshi,Nishimura, Hiroaki,Ogino, Takashi,Seki, Nobuo,Sugiyama, Aiko,Matsuo, Masaaki
, p. 2427 - 2430 (2007/10/03)
A series of quinoline-3-carbothioamides and their analogues was prepared via four synthetic routes and evaluated for their antinephritic and immunomodulating activities. The optimal compound 9g strongly inhibited the T-cell independent antibody production in mice immunized with TNP-LPS and was highly effective in two nephritis models, namely chronic graft-versus-host disease and autoimmune MRL/l mice.
