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 GI 50 values of 1.34 μM and 2.30 μM 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 CCRF cells at concentration of 50 μM.
Original language | English (US) |
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Pages (from-to) | 4853-4858 |
Number of pages | 6 |
Journal | European Journal of Medicinal Chemistry |
Volume | 46 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2011 |
Externally published | Yes |
Keywords
- Anticancer
- Cell proliferation
- Inhibitor
- KX-2
- Src kinase
- Thiazole
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Pharmacology