Multistep solid-phase synthesis of an antibiotic and receptor tyrosine kinase inhibitors using the traceless phenylhydrazide linker.
The hydrazide group is an oxidatively cleavable traceless linker for solid-phase chemistry. This linker technology was used to develop a multistep solid-phase synthesis of an antibiotic that is active against Mycobacterium tuberculosis. Furthermore, we describe an efficient method for the traceless synthesis of 2-aminothiazoles that display dual inhibitory activity against the receptor tyrosine kinases VEGFR-2 and Tie-2. The synthesis method proceeds through 9 steps on the solid phase and should give access to a much larger library of 2-aminothiazoles, from which a new class of anti-angiogenesis drugs may be developed.
Stieber
Frank
F
Max-Planck-Institut für Molekulare Physiologie, Abteilung Chemische Biologie, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
Grether
Uwe
U
Mazitschek
Ralph
R
Soric
Natascha
N
Giannis
Athanassios
A
Waldmann
Herbert
H
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D020794:Receptor Protein-Tyrosine Kinases