Design, Synthesis and Antiproliferative Activity of 2-Acetamidothiazole-5- carboxamide Derivatives

Title:Design, Synthesis and Antiproliferative Activity of 2-Acetamidothiazole-5- carboxamide Derivatives

Volume: 8 Issue: 4

Author(s): Wukun Liu, Jinpei Zhou, Yu Zheng, Fan Qi, Huibin Zhang, Hai Qian, Jing Wang, Yanhua Cheng and Ronald Gust

Affiliation:

Keywords: Dasatinib, Antiproliferative Activity, SRC Kinase Inhibitor, Synthesis, Structure-Activity Relationship Studies, pyrimidin-4-ylamino, MDA-MB 231, HT-29 cells, ABL kinase, chronic myeloid leukaemia

Abstract: In order to develop a new series of dual inhibitors of SRC and ABL, and to investigate whether the pyrimidin- 4-ylamino moiety is critical for dasatinib’s activity, acetyl substitution was adopted as alternate scaffold at the 2-amino group. Eighteen novel dasatinib derivatives were developed by a parallel synthesis approach and evaluated for their antiproliferative effects. Preliminary tests showed that some of the target compounds IId, IIe and IIf manifested strong antiproliferative activity against MCF-7, MDA-MB 231 and HT-29 cells. Easpecially IId proved to be the most potent compound. Structure-activity relationship studies indicate that the introduction of acetyl substitution as alternate scaffold of pyrimidin-4-ylamino reduced the activity.

Cite this article as:

Liu Wukun, Zhou Jinpei, Zheng Yu, Qi Fan, Zhang Huibin, Qian Hai, Wang Jing, Cheng Yanhua and Gust Ronald, Design, Synthesis and Antiproliferative Activity of 2-Acetamidothiazole-5- carboxamide Derivatives, Medicinal Chemistry 2012; 8 (4) . https://dx.doi.org/10.2174/157340612801216418