- BENZOFURAN-BASED N-ACYLHYDRAZONE DERIVATIVES AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME
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A benzofuran-based N-acylhydrazone derivative according to the present invention has an excellent anticancer effect while having low toxicity and excellent solubility, and, thus, a pharmaceutical composition comprising the derivative can be usefully used to prevent or treat a cell proliferative disorder including various cancers. To this end, the present invention provides a compound represented by chemical formula 1, a stereoisomer thereof, or a pharmaceutically acceptable salt thereof.
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Paragraph 0220-0223
(2021/02/02)
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- LRRK2 INHIBITORS
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Provided herein are compounds that inhibit or partially inhibit the activity of leucine rich repeat kinases. Also provided herein are methods of treatment of CNS disorders comprising administration of inhibitors of leucine rich repeat kinases.
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- Synthesis, structure-activity relationship and crystallographic studies of 3-substituted indolin-2-one RET inhibitors
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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.
- 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
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experimental part
p. 1482 - 1496
(2010/04/29)
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- Synthesis and antiproliferative activities of isoindigo and azaisoindigo derivatives
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In the course of structure-activity relationship studies, diversely substituted 1-(β- d-acetylatedglucopyranosyl)isoindigo derivatives were prepared from indolines. New 7′-azaisoindigo analogues were also synthesized by coupling a glycosylated isatine and a 7-azaindolin-2-one derivative. Compounds containing a 7′-azaisoindigo framework have never been described before. To get an insight into the substitution pattern required for the best biological potencies, their antiproliferative activities were evaluated toward a human buccal carcinoma cell line (KB) and two human myeloid leukaemia cell lines (K562, HL60).
- Bouchikhi, Fadoua,Anizon, Fabrice,Moreau, Pascale
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p. 755 - 762
(2008/09/20)
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