Paper
Design, Synthesis, and Biological Evaluation of Aminoboronic Acids as Growth‐Factor Receptor Inhibitors of EGFR and VEGFR‐1 Tyrosine Kinases
Published Apr 2, 2004 · Toru Asano, Hiroyuki Nakamura, Y. Uehara
ChemBioChem
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Abstract
A series of aminoboronic acids was synthesized based on the structure of lavendustin pharmacophore 1. Their inhibitory activities against the epidermal growth‐factor receptor (EGFR) and vascular endothelial growth‐factor receptor‐1 (VEGFR‐1, Flt‐1) protein tyrosine kinases, and various protein kinases, PKA, PKC, PTK, and eEF2K were evaluated. Selective inhibition activities were observed in a series of aminoboronic acids. 4‐Methoxy‐3‐((2‐ methoxyphenylamino)methyl)phenylboronic acid 10 inhibited EGFR tyrosine kinase, whereas 4‐(2,5‐dihydroxybenzylamino)phenylboronic acid 12 inhibited Flt‐1 protein kinase, although lavendustin pharmacophore 1 inhibited both EGFR and Flt‐1 kinases at a compound concentration of 1.0 μg mL−1. The selective inhibition of EGFR by 10 is considered to be due to the substitution of the dihydroxy groups on the benzyl moiety for a boronic acid group at the para position, whereas the selective inhibition of Flt‐1 by 12 is due to the substitution of the carboxyl group on the aniline moiety in the lavendustin pharmacophore 1 for a boronic acid group.
Aminoboronic acids show selective inhibition of EGFR and VEGFR-1 tyrosine kinases, offering potential as growth-factor receptor inhibitors.
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