Synthesis and Biological Activities of 2-Amino-thiazole-5-carboxylic Acid Phenylamide Derivatives

• Published in: Archiv der Pharmazie (Weinheim) 2011-07, Vol.344 (7), p.451-458
• Main Authors: Liu, Wukun, Zhou, Jinpei, Qi, Fan, Bensdorf, Kerstin, Li, Zhiyu, Zhang, Huibin, Qian, Hai, Huang, Wenlong, Cai, Xueting, Cao, Peng, Wellner, Anja, Gust, Ronald
• Format: Article
• Language: English
• Subjects: Amides - chemical synthesis; Amides - chemistry; Amides - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Proliferation - drug effects; Colonic Neoplasms - drug therapy; Colonic Neoplasms - pathology; Combinatorial Chemistry Techniques; Dasatinib; Female; HT29 Cells; Humans; Inhibitory Concentration 50; Leukemia - drug therapy; Leukemia - pathology; Protein tyrosine kinases; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Structure-Activity Relationship; Synthesis; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201000281

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