Synthesis and Biological Activities of 2‐Amino‐thiazole‐5‐carboxylic Acid Phenylamide Derivatives
- 20 May 2011
- journal article
- research article
- Published by Wiley in Archiv der Pharmazie
- Vol. 344 (7) , 451-458
Abstract
In an attempt to develop potent and selective anti‐tumor drugs, a series of novel 2‐amino‐thiazole‐5‐carboxylic acid phenylamide derivatives were designed based on the structure of dasatinib. All compounds were synthesized by a systematic combinatorial chemical approach. Biological evaluation revealed that N‐(2‐chloro‐6‐methylphenyl)‐2‐(2‐(4‐methylpiperazin‐1‐yl)acetamido)thiazole‐5‐carboxamide (6d) exhibited high antiproliferative potency on human K563 leukemia cells comparable to dasatinib. Against mammary and colon carcinoma cells 6d was either inactive (MDA‐MB 231) or distinctly less active (MCF‐7 and HT‐29: IC50 = 20.2 and 21.6 µM, respectively). Dasatinib showed at each cell line IC50 < 1 µM. The results of this structure activity relationship study clearly documented that the pyrimidin‐4‐ylamino core of dasatinib is responsible for the anti‐tumor activity against non‐leukemia cell lines.Keywords
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