Synthesis and biological activities of 2-amino-thiazole-5-carboxylic acid phenylamide derivatives
| Autor: | Kerstin Bensdorf, Wukun Liu, Xueting Cai, Ronald Gust, Hai Qian, Fan Qi, Huibin Zhang, Anja Wellner, Jinpei Zhou, Zhiyu Li, Wenlong Huang, Peng Cao |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Stereochemistry
Carboxylic acid Dasatinib Pharmaceutical Science Antineoplastic Agents Breast Neoplasms chemistry.chemical_compound Inhibitory Concentration 50 Structure-Activity Relationship Colon carcinoma hemic and lymphatic diseases Cell Line Tumor Drug Discovery medicine Structure–activity relationship Potency Combinatorial Chemistry Techniques Humans Thiazole Cell Proliferation chemistry.chemical_classification Leukemia medicine.disease Amides Thiazoles Pyrimidines Biochemistry chemistry Cell culture Colonic Neoplasms Female HT29 Cells medicine.drug |
| Zdroj: | Archiv der Pharmazie. 344(7) |
| ISSN: | 1521-4184 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text