BIOMAT Database Logo BIOMAT Database Logo

Discovery of 6-phenylimidazo[2,1-b]thiazole derivatives as a new type of FLT3 inhibitors. 2015

Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Sichuan 610041, China.

In this investigation, a series of 6-phenylimidazo[2,1-b]thiazole derivatives were synthesized. Structure-activity relationship (SAR) analysis of these compounds based on cellular assays led to the discovery of a number of compounds that showed potent activity against FLT3-dependent human acute myeloid leukemia (AML) cell line MV4-11, but very weak or no activity against FLT3-independent human cervical cancer cell line Hela. FLT3 kinase inhibition assays were then performed on the three most active compounds. Among these compounds, 6-(4-(3-(5-(tert-butyl)isoxazol- 3-yl)ureido)phenyl)-N-(3-(dimethylamino)propyl)imidazo[2,1-b]thiazole-3-carboxamide (19) exhibited the highest potency in both cellular (MV4-11, IC50: 0.002 μM) and enzymatic (FLT3, IC50: 0.022 μM) assays. Further in-depth in vitro anti-AML activity and mechanism of action studies were carried out on compound 19.

UI MeSH Term Description Entries
D010671 Phenylurea Compounds Compounds that include the amino-N-phenylamide structure. Phenylcarbamides,Phenylurea Derivatives,Compounds, Phenylurea,Derivatives, Phenylurea
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D006367 HeLa Cells The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for, among other things, VIRUS CULTIVATION and PRECLINICAL DRUG EVALUATION assays. Cell, HeLa,Cells, HeLa,HeLa Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013844 Thiazoles Heterocyclic compounds where the ring system is composed of three CARBON atoms, a SULFUR and NITROGEN atoms. Thiazole
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D047428 Protein Kinase Inhibitors Agents that inhibit PROTEIN KINASES. Protein Kinase Inhibitor,Inhibitor, Protein Kinase,Inhibitors, Protein Kinase,Kinase Inhibitor, Protein,Kinase Inhibitors, Protein

Related Publications

Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Synthesis and antimicrobial activity of new 6-phenylimidazo[2,1-b]thiazole derivatives.
January 2000, Bollettino chimico farmaceutico,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Imidazo[2,1-b]thiazole derivatives as new inhibitors of 15-lipoxygenase.
November 2014, European journal of medicinal chemistry,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Chloro(ethylenediamine)(6-phenylimidazo-[2,1-b]thiazole-N7)platinum(II) nitrate.
February 1996, Acta crystallographica. Section C, Crystal structure communications,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Identification of benzo[d]pyrrolo[2,1-b]thiazole derivatives as CENP-E inhibitors.
November 2019, Biochemical and biophysical research communications,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Imidazo[2,1-b]thiazole guanylhydrazones as RSK2 inhibitors.
September 2011, European journal of medicinal chemistry,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Design, Synthesis and Biological Evaluation of New Imidazo[2,1-b]Thiazole Derivatives as Selective COX-2 Inhibitors.
January 2018, Iranian journal of pharmaceutical research : IJPR,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Anti-inflammatory effect of 3-fluorophenyl pyrimidinylimidazo[2,1-b]thiazole derivatives as p38α inhibitors.
October 2023, Bioorganic chemistry,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Design, synthesis and biological evaluation of imidazo[2,1-b]thiazole and benzo[d]imidazo[2,1-b]thiazole derivatives as Mycobacterium tuberculosis pantothenate synthetase inhibitors.
March 2016, Bioorganic & medicinal chemistry,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
A new synthesis of 6-phenyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole.
April 1968, The Journal of organic chemistry,
Xing-Dong Lin, and Hui-Wen Yang, and Shuang Ma, and Wei-Wei Li, and Chun-Hui Zhang, and Wen-Jing Wang, and Rong Xiang, and Lin-Li Li, and Sheng-Yong Yang
Discovery of New Imidazo[2,1-b]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising In Vitro and In Vivo Anti-melanoma Activity.
May 2021, Journal of medicinal chemistry,
Copied contents to your clipboard!