83846-78-0Relevant articles and documents
Indole derivatives, Abl kinase inhibiting composition and pharmaceutical compositions for prevention and treatment of abnormal cell growth diseases comprising the same
-
Paragraph 0259; 0261; 0262; 0263, (2016/10/10)
PURPOSE: An indole derivative compound, and an Abl kinase inhibitor composition and a pharmaceutical composition for preventing and treating abnormal cell growth diseases containing the same are provided to treat diseases caused by abnormal cell growth, function, or behavior, especially cancer, immune diseases, cardiovascular diseases, viral infectious diseases, inflammatory diseases, endocrine diseases, and neurological diseases. CONSTITUTION: An indole derivative of chemical formula 1 or a pharmaceutically acceptable salt is provided. A pharmaceutical composition for suppressing wild type Abl kinase and mutant type Abl (T315I) kinase contains the compound as an active ingredient and a pharmaceutically acceptable carrier or diluents. A pharmaceutical composition for treating proliferative diseases, immune diseases, cardiovascular diseases, neurological diseases, inflammatory diseases, endocrine diseases, or viral infectious diseases contains the compound as an active ingredient and a pharmaceutically acceptable carrier or diluents.
Discovery of new benzothiazole-based inhibitors of breakpoint cluster region-abelson kinase including the T315i mutant
Hong, Seunghee,Kim, Jinhee,Yun, Sun-Mi,Lee, Hyunseung,Park, Yoonsu,Hong, Soon-Sun,Hong, Sungwoo
, p. 3531 - 3545 (2013/06/27)
The existence of drug resistance caused by mutations in the break-point cluster region-Abelson tyrosine kinase (Bcr-Abl) kinase domain remains a clinical challenge due to limited effective treatment options for chronic myeloid leukemia (CML). Herein we report a novel series of benzothiazole-based inhibitors that are effective against wild-type and T315I mutant Bcr-Abl kinases. The original hit compound, nocodazole, was extensively modified through a structure-based drug design strategy, especially by varying the groups at the C2 and C6 positions of the scaffold. In addition, the introduction of water-solubilizing groups at the terminal ethyl group resulted in enhanced physicochemical properties and potency in cellular inhibition. Several compounds inhibited the kinase activity of both wild-type Bcr-Abl and the T315I mutant with IC50 values in the picomolar range and exhibited good antiproliferative effects on Ba/F3 cell lines transformed with either wild-type or T315I mutant Bcr-Abl.