1049685-21-3Relevant articles and documents
Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL)
Borkin, Dmitry,Pollock, Jonathan,Kempinska, Katarzyna,Purohit, Trupta,Li, Xiaoqin,Wen, Bo,Zhao, Ting,Miao, Hongzhi,Shukla, Shirish,He, Miao,Sun, Duxin,Cierpicki, Tomasz,Grembecka, Jolanta
, p. 892 - 913 (2016/02/23)
Development of potent small molecule inhibitors of protein-protein interactions with optimized druglike properties represents a challenging task in lead optimization process. Here, we report synthesis and structure-based optimization of new thienopyrimidine class of compounds, which block the protein-protein interaction between menin and MLL fusion proteins that plays an important role in acute leukemias with MLL translocations. We performed simultaneous optimization of both activity and druglike properties through systematic exploration of substituents introduced to the indole ring of lead compound 1 (MI-136) to identify compounds suitable for in vivo studies in mice. This work resulted in the identification of compound 27 (MI-538), which showed significantly increased activity, selectivity, polarity, and pharmacokinetic profile over 1 and demonstrated a pronounced effect in a mouse model of MLL leukemia. This study, which reports detailed structure-activity and structure-property relationships for the menin-MLL inhibitors, demonstrates challenges in optimizing inhibitors of protein-protein interactions for potential therapeutic applications.
2, 3-SUBSTITUTED INDOLE DERIVATIVES FOR TREATING VIRAL INFECTIONS
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Page/Page column 203, (2009/04/25)
The present invention relates to 2,3-Substituted Indole Derivatives, compositions comprising at least one 2,3-Substituted Indole Derivative, and methods of using the 2,3-Substituted Indole Derivatives for treating or preventing a viral infection or a viru
Syntheses of 4-(indole-3-yl)quinazolines - A new class of epidermal growth factor receptor tyrosine kinase inhibitors
Lueth, Anja,Loewe, Werner
, p. 1478 - 1488 (2008/09/21)
The epidermal growth factor (EGF) family of membrane receptors has been identified as a key element in the complex signaling network that is utilized by various classes of cell-surface receptors. The synthesis and pharmacological results of 4-(indole-3-yl)quinazolines are described. The synthesized compounds are new high potent EGFR-tyrosine kinase inhibitors with excellent cytotoxic properties at different cell lines. Furthermore the 4-(indole-3-yl)quinazolines show some tendencies to inhibit the HER-2 TK, too. Moreover this substance class has remarkable strong fluorescence properties.
