2-Aminothiazole Derivative as a New Class of TrkA Kinase Inhibitor

Abstract

Cancer (also called a malignant neoplasm) is a class of diseases in which a group of cells show uncontrolled cell growth, invasion and occasionally metastasis, and is a major public health problem worldwide. However, drug discovery and the development of cancer therapeutics take many years before a patient can benefit from a new drug. This time period is too long and needs to be shortened so patients can benefit quickly from new technologies and product development ideas. Combinatorial chemistry is a widely used technique for accelerating drug discovery and development, in which tools and technologies from biology and chemistry are used in a parallel manner. It was reported that many 2-aminothiazoles exhibit antitumor activity through the inhibition of kinases, 1-3 Therefore, in the course of searching for anticancer agents, 2-aminothiazole derivatives were recently prepared by varying the 2-amino position and 5-substituted group in a high-speed parallel format according to the literature procedure, as shown in Scheme 1. 4 Among synthesized, compound H154 exhibited significant cell growth inhibition against Hep3B cells with an IC50 value of 0.040 µM by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] (MTT) assay. However, the specific cellular mechanism of action of this compound is unclear. 5