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Upstream product

• 49844-90-8 4-Chloro-2-methylthiopyrimidine 
• 2507-80-4 6-(4-methoxyphenyl)imidazo[2,1-b][1,3]thiazole 
• 2632-13-5 2-Bromo-4'-methoxyacetophenone 

Relevant academic research and scientific papers

Discovery of first-in-class imidazothiazole-based potent and selective ErbB4 (HER4) kinase inhibitors

This article reports on novel imidazothiazole derivatives as first-in-class potent and selective ErbB4 (HER4) inhibitors. There are no other reported selective inhibitors of this kinase in the literature, that's why they are considered as first-in-class. In addition, none of the reported non-selective ErbB4 inhibitors possesses imidazothiazole nucleus in its structure. Therefore, there is novelty in this work in both kinase selectivity and chemical structure. Compounds Ik and IIa are the most potent ErbB4 kinase inhibitor (IC50 = 15.24 and 17.70 nM, respectively). Compound Ik showed promising antiproliferative activity. It is selective towards cancer cell lines than normal cells. Its ability to penetrate T-47D cell membrane and inhibit ErbB4 kinase inside the cells has been confirmed. Moreover, both compound Ik and IIa have additional merits such as weak potency against hERG ion channels and against CYP 3A4 and 2D6. Molecular docking and dynamic simulation studies were carried out to explain binding interactions.

Discovery of New Imidazo[2,1- b]thiazole Derivatives as Potent Pan-RAF Inhibitors with Promising in Vitro and in Vivo Anti-melanoma Activity

BRAF is an important component of MAPK cascade. Mutation of BRAF, in particular V600E, leads to hyperactivation of the MAPK pathway and uncontrolled cellular growth. Resistance to selective inhibitors of mutated BRAF is a major obstacle against treatment of many cancer types. In this work, a series of new (imidazo[2,1-b]thiazol-5-yl)pyrimidine derivatives possessing a terminal sulfonamide moiety were synthesized. Pan-RAF inhibitory effect of the new series was investigated, and structure-activity relationship is discussed. Antiproliferative activity of the target compounds was tested against the NCI-60 cell line panel. The most active compounds were further tested to obtain their IC50 values against cancer cells. Compound 27c with terminal open chain sulfonamide and 38a with a cyclic sulfamide moiety showed the highest activity in enzymatic and cellular assay, and both compounds were able to inhibit phosphorylation of MEK and ERK. Compound 38a was selected for testing its in vivo activity against melanoma. Cellular and animal activities are reported.