de novo design and synthesis of N-benzylanilines as new candidates for VEGFR tyrosine kinase inhibitors

Masaharu Uno; Hyun Seung Ban; Wataru Nabeyama; Hiroyuki Nakamura

doi:10.1039/b719959g

de novo design and synthesis of N-benzylanilines as new candidates for VEGFR tyrosine kinase inhibitors

Org Biomol Chem. 2008 Mar 21;6(6):979-81. doi: 10.1039/b719959g. Epub 2008 Feb 11.

Authors

Masaharu Uno¹, Hyun Seung Ban, Wataru Nabeyama, Hiroyuki Nakamura

Affiliation

¹ Department of Chemistry, Faculty of Science, Gakushuin University, 1-5-1 Mejiro, Toshima-ku, Tokyo 171-8588, Japan.

PMID: 18327319
DOI: 10.1039/b719959g

Abstract

N-Benzylanilines were designed and synthesized as vascular endothelial growth factor (VEGF)-2 inhibitors using de novo drug design systems based on the X-ray structure of VEGFR-2 kinase domain. Among compounds synthesized, compound showed the most potent inhibitory activity toward VEGFR-2 (KDR) tyrosine kinase and its IC(50) value was 0.57 microM.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aniline Compounds / chemical synthesis*
Aniline Compounds / chemistry
Aniline Compounds / pharmacology
Cell Line
Dose-Response Relationship, Drug
Drug Design*
Drug Evaluation, Preclinical
Endothelium, Vascular / drug effects
Endothelium, Vascular / enzymology
Humans
Models, Biological
Molecular Structure
Phosphorylation / drug effects
Protein Structure, Tertiary / drug effects
Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors*

Substances

Aniline Compounds
Vascular Endothelial Growth Factor Receptor-2
benzylaniline