KDR inhibitor with the intramolecular non-bonded interaction: conformation-activity relationships of novel indole-3-carboxamide derivatives

Takahiro Honda; Hironori Nagahara; Hiroyuki Mogi; Masakazu Ban; Hiroyuki Aono

doi:10.1016/j.bmcl.2011.01.063

KDR inhibitor with the intramolecular non-bonded interaction: conformation-activity relationships of novel indole-3-carboxamide derivatives

Bioorg Med Chem Lett. 2011 Mar 15;21(6):1782-5. doi: 10.1016/j.bmcl.2011.01.063. Epub 2011 Jan 22.

Authors

Takahiro Honda¹, Hironori Nagahara, Hiroyuki Mogi, Masakazu Ban, Hiroyuki Aono

Affiliation

¹ Research and Development Center, Santen Pharmaceutical Co. Ltd, Ikoma-shi, Nara, Japan. hondat@ms.naist.jp

PMID: 21324683
DOI: 10.1016/j.bmcl.2011.01.063

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.

MeSH terms

Enzyme Inhibitors / chemistry*
Enzyme Inhibitors / pharmacology
Indoles / chemistry*
Indoles / pharmacology
Models, Molecular
Molecular Structure
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

Enzyme Inhibitors
Indoles
Vascular Endothelial Growth Factor Receptor-2