Synthesis of<i> N</i>-substituted 4-phenyl-2-aminothiazole derivatives and investigation of their inhibition properties against<i> h</i>CA I, II, and AChE enzymes

In this study, thiazole derivatives containing sulphonamide, amide, and phenyl amino groups were synthesized to protect the free amino groups of 5-methyl-4-phenyl-2-aminothiazole and 4-phenyl-2-aminothiazole. Halogenated reactions of N-protected thiazole derivatives have been investigated. LCMS, FT-IR, 1 H NMR, and 13 C NMR spectroscopy techniques were used to elucidate the structures of the synthesized compounds. Inhibition effects of the N-protected thiazole derivatives against human carbonic anhydrase I, II (hCA h CA I, h CA II), and acetylcholinesterase (AChE) were investigated. The best results among the synthesized N-protected thiazole derivatives showed Ki i values in the range of 46.85-587.53 nM against h CA I, 35.01-578.06 nM against h CA II, and in the range of 19.58-226.18 nM against AChE. Furthermore, in silico studies with the target enzyme of the thiazole derivatives (9 and 11), , which showed the best results experimentally, have examined the binding interactions of the related compounds at the enzyme active site.