KDR inhibitor with the intramolecular non-bonded interaction: conformation-activity relationships of novel indole-3-carboxamide derivatives |
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Authors: | Honda Takahiro Nagahara Hironori Mogi Hiroyuki Ban Masakazu Aono Hiroyuki |
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Institution: | a Research and Development Center, Santen Pharmaceutical Co. Ltd, 8916-16 Takayama-cho Ikoma-shi, Nara 630-0101, Japan b Graduate School of Materials Sciences, Nara Institute of Science and Technology, 8916-5 Takayama-cho Ikoma-shi, Nara 630-0192, Japan |
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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).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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Keywords: | KDR inhibitor Intramolecular non-bonded interaction Non-bonded S-O interaction Pseudo ring design Indole Intramolecular hydrogen bonding X-ray crystallography |
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