title: Design of potent IGF1-R inhibitors related to bis-azaindoles.
abstract: 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.
authors.affiliation: Medicinal Chemistry, Sanofi-Aventis, 13 Quai Jules Guesde, 94300 Vitry-sur-Seine, France.
authors.forename: Conception
authors.initials: C
authors.lastname: Nemecek
authors.forename: William A
authors.initials: WA
authors.lastname: Metz
authors.forename: Sylvie
authors.initials: S
authors.lastname: Wentzler
authors.forename: Fa-Xiang
authors.initials: FX
authors.lastname: Ding
authors.forename: Corinne
authors.initials: C
authors.lastname: Venot
authors.forename: Catherine
authors.initials: C
authors.lastname: Souaille
authors.forename: Anne
authors.initials: A
authors.lastname: Dagallier
authors.forename: Sébastien
authors.initials: S
authors.lastname: Maignan
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Guilloteau
authors.forename: François
authors.initials: F
authors.lastname: Bernard
authors.forename: Alain
authors.initials: A
authors.lastname: Henry
authors.forename: Sandrine
authors.initials: S
authors.lastname: Grapinet
authors.forename: Dominique
authors.initials: D
authors.lastname: Lesuisse
mesh_terms: D000818:Animals; D001665:Binding Sites; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D013329:Structure-Activity Relationship
chemical_list: D007211:Indoles; D047428:Protein Kinase Inhibitors; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I