Design of Potent IGF1-R Inhibitors Related to Bis-azaindoles

From an azaindole lead, identified in high throughput screen, a series of potent bis‐azaindole inhibitors of IGF1‐R have been synthesized using rational drug design and SAR based on a in silico binding mode hypothesis. Although the resulting compounds produced the expected improved potency, the mode...

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Veröffentlicht in:	Chemical biology & drug design 2010-08, Vol.76 (2), p.100-106
Hauptverfasser:	Nemecek, Conception, Metz, William A., Wentzler, Sylvie, Ding, Fa-Xiang, Venot, Corinne, Souaille, Catherine, Dagallier, Anne, Maignan, Sébastien, Guilloteau, Jean-Pierre, Bernard, François, Henry, Alain, Grapinet, Sandrine, Lesuisse, Dominique
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Binding Sites Cell Line, Tumor Crystallography, X-Ray Drug Design drug discovery Drug Screening Assays, Antitumor enzyme structure Humans Indoles - chemical synthesis Indoles - chemistry Indoles - pharmacokinetics Insulin-Like Growth Factor I - antagonists & inhibitors Insulin-Like Growth Factor I - metabolism kinase Mice phosphatase Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacokinetics Structure-Activity Relationship structure-based drug design
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Beschreibung
Zusammenfassung:	From an azaindole lead, identified in high throughput screen, a series of potent bis‐azaindole inhibitors of IGF1‐R have been synthesized using rational drug design and SAR based on a in silico binding mode hypothesis. Although the resulting compounds produced the expected improved potency, the model was not validated by the co‐crystallization experiments with IGF1‐R.
ISSN:	1747-0277 1747-0285
DOI:	10.1111/j.1747-0285.2010.00991.x