Thiazolyl N-Benzyl-Substituted Acetamide Derivatives: Synthesis, Src Kinase Inhibitory and Anticancer Activities

Authors

Asal Fallah-Tafti, Tehran University of Medical SciencesFollow
Alireza Foroumadi, Tehran University of Medical SciencesFollow
Rakesh Tiwari, Chapman UniversityFollow
Amir Nasrolahi Shirazi, Chapman UniversityFollow
David G. Hangauer, Kinex Pharmaceuticals
Yahao Bu, Kinex Pharmaceuticals
Tahmineh Akbarzadeh, Tehran University of Medical SciencesFollow
Keykavous Parang, Chapman UniversityFollow
Abbas Shafiee, Tehran University of Medical SciencesFollow

Document Type

Article

Publication Date

2011

Abstract

KX2-391 (KX-01/Kinex Pharmaceuticals), N-benzyl-2-(5-(4-(2-morpholinoethoxy)phenyl)pyridin-2-yl)acetamide, is a highly selective Src substrate binding site inhibitor. To understand better the role of pyridine ring and N-benzylsubstitution in KX2-391 and establish the structure-activity relationship, a number of N-benzyl substituted (2-morpholinoethoxy)phenyl)thiazol-4-yl)acetamide derivatives containing thiazole instead of pyridine were synthesized and evaluated for Src kinase inhibitory activities. The unsubstituted N-benzyl derivative (8a) showed the inhibition of c-Src kinase with GI50 values of 1.34 μM and 2.30 M in NIH3T3/c-Src527F and SYF/c-Src527F cells, respectively. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), breast carcinoma (BT-20), and leukemia (CCRF-CEM) cells. 4-Fluorobenzylthiazolyl derivative 8b exhibited 64-71% inhibition in the cell proliferation of BT-20 and CCR5 cells at concentration of 50 μM.

Comments

NOTICE: this is the author’s version of a work that was accepted for publication in European Journal of Medicinal Chemistry. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in European Journal of Medicinal Chemistry, volume 46. issue 10, in 2011. DOI: 10.1016/j.ejmech.2011.07.050

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Recommended Citation

Fallah-Tafti, Asal, et al. "Thiazolyl N-benzyl-substituted acetamide derivatives: synthesis, Src kinase inhibitory and anticancer activities." European journal of medicinal chemistry 46.10 (2011): 4853-4858. doi: 10.1016/j.ejmech.2011.07.050

Copyright

Elsevier

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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.