title: KDR inhibitor with the intramolecular non-bonded interaction: conformation-activity relationships of novel indole-3-carboxamide derivatives.
abstract: We previously reported that compound 1, having a similar conformation to PTK787 (2) by forming a pseudo ring structure with an intramolecular non-bonded S-O interaction, exhibited a potent inhibitory activity against VEGFR2 tyrosine kinase (KDR). Applying the ideas of pseudo ring formations, we have designed three types of novel indole carboxamide derivatives 5-7 with an intramolecular hydrogen bonding or non-bonded S-O interaction. We describe the design and synthesis of 5-7, and also discuss the relationships of their KDR inhibitory activity and conformations that were stabilized by their intramolecular non-bonded interactions.
authors.affiliation: Research and Development Center, Santen Pharmaceutical Co. Ltd, Ikoma-shi, Nara, Japan. hondat@ms.naist.jp
authors.forename: Takahiro
authors.initials: T
authors.lastname: Honda
authors.forename: Hironori
authors.initials: H
authors.lastname: Nagahara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mogi
authors.forename: Masakazu
authors.initials: M
authors.lastname: Ban
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aono
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D015394:Molecular Structure; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D040301:Vascular Endothelial Growth Factor Receptor-2