Imidazopyrazines

Publications describing Btk inhibitors are scarce [39], but a recent upturn in patent activity points to intensifying medicinal chemistry efforts. The field is dominated by two classes irreversible inhibitors and reversible inhibitors which are based on an imidazopyrazine-amide scaffold (Figure 2). 

In addition to preceding inhibitors, a number of patent specifications claim protein kinase inhibitors active against IGF-IR (e.g., 4-(pyrazol-3-ylamino)pyrimidines, imidazopyrazines, 2,4-pyrimidinediamines, pyrazolyl-pyrimidinyl-amino derivatives and indolesulfonamides). We can expect that... 

The imidazopyrazine substructure occurs in luciferins from a wide range of organisms living in the sea and in ostracod crustaceans, e.g. Cypridina. The chemistry of the luminescent effect in these systems involves reaction with oxygen to form a stable cyclic dioxetanone, similar to the hrefly luciferin as indicated in (3.108). 

A modified Lossen rearrangement occurs when 2-aminopyrazine-carbohydroxamic acid (77) is treated with benzenesulfonyl chloride and the imidazopyrazine (78) is formed in good yield.253... 

Lewis bases toward the metal ions. The OlO must be the actual center of the Lewis base and coordinates to the metal ion, because of the zwitter-ionic character (II) of an imidazopyrazinone. An enhancement of the Lewis acid/base interaction in the metal-ion complexes causes changes in the n-electronic character and increases the aromatic imidazopyrazine property, resulting in the blue shift of the lowest energy bands. Therefore, imidazopyrainone derivatives are potentially applicable as indicators for the Lewis acidity of metal ions. The design of 1,2- and l,3-bis(2-phenylimidazopyzinon-7-ylmethyl)benzene derivatives demonstrated that complexation with the metal ion is enhanced by chelate effects. 

Reductive removal of the benzyloxycarbonyl group on the side chain of the oxazolone 54 gives the unstable amino compound 55. On standing, or more rapidly by treatment with acetic anhydride, the oxazolone gave a compound originally formulated as the imidazopyrazine 56, which was... 

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