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Synthesis and Biological Activities of 2‐Amino‐thiazole‐5‐carboxylic Acid Phenylamide Derivatives
Author(s) -
Liu Wukun,
Zhou Jinpei,
Qi Fan,
Bensdorf Kerstin,
Li Zhiyu,
Zhang Huibin,
Qian Hai,
Huang Wenlong,
Cai Xueting,
Cao Peng,
Wellner Anja,
Gust Ronald
Publication year - 2011
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201000281
Subject(s) - dasatinib , thiazole , chemistry , carboxylic acid , carboxamide , stereochemistry , cell culture , potency , biological activity , structure–activity relationship , chemical synthesis , leukemia , in vitro , pharmacology , combinatorial chemistry , biochemistry , receptor , medicine , biology , tyrosine kinase , genetics
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: IC 50 = 20.2 and 21.6 µM, respectively). Dasatinib showed at each cell line IC 50 < 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.