199328-10-4Relevant articles and documents
Synthesis and characterization of amino acid substituted sunitinib analogues for the treatment of AML
Nemes, Zoltán,Takács-Novák, Krisztina,V?lgyi, Gergely,Valko, Klara,Béni, Szabolcs,Horváth, Zoltán,Szokol, Bálint,Breza, Nóra,Dobos, Judit,Szántai-Kis, Csaba,Illyés, Eszter,Boros, Sándor,Kok, Robbert Jan,?rfi, László
, p. 2391 - 2398 (2018)
Acute myeloid leukemia (AML) is the most common type of leukemia in adults. Sunitinib, a multikinase inhibitor, was the first Fms-like tyrosine kinase 3 (FLT3) inhibitor clinically used against AML. Off-target effects are a major concern for multikinase inhibitors. As targeted delivery may reduce such undesired side effects, our goal was to develop novel amino acid substituted derivatives of sunitinib which are potent candidates to be used conjugated with antibodies and peptides. In the current paper we present the synthesis, physicochemical and in vitro characterization of sixty two Fms-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutant kinase inhibitors, bearing amino acid moieties, fit to be conjugated with peptide-based delivery systems via their carboxyl group. We determined the solubility, pKa, CHI and LogP values of the compounds along with their inhibition potential against FLT3-ITD mutant kinase and on MV4-11 cell line. The ester derivatives of the compounds inhibit the growth of the MV4-11 leukemia cell line at submicromolar concentration.
INDOLINONE DERIVATIVES AND PROCESS FOR THEIR MANUFACTURE
-
Page/Page column 15; 5, (2009/07/17)
The present invention relates to specific indolinone derivatives, namely the compounds of formula, in which R1 represents an hydrogen atom or a group, and R2 and R3 each represent an hydrogen atom or R2 and R3 taken together represent a group, with the proviso that when R1 represents an hydrogen atom R2 and R3 taken together represent a group, and to a process for their manufacture.
3-(PIPERAZINYLBENZYLIDENYL)-2-INDOLINONE COMPOUNDS AND DERIVATIVES AS PROTEIN TYROSINE KINASE INHIBITORS
-
, (2008/06/13)
-