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

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).1 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.

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