Besides the above compounds, further early examples of (presumably) covalent
JAK3 inhibitors have been reported in the patent literature. For example, a set of
druglike acrylamide-derived JAK3 inhibitors were claimed as early as 2005 in a
patent from Cytopia Ltd. (Fig. 7) [40]. These inhibitors possessed selectivity for
Fig. 5 Naphthyl(β-aminoethyl)ketones and analogous compounds
Fig. 6 Macrocyclic
Mannich base NC-1153 and
α,β-unsaturated analog
EP009
Fig. 7 Electrophilic JAK3 inhibitors from Cytopia Ltd. (a) General structure. (b) Selected example 31
and analog 32, which was later crystallized in complex with JAK3 by Goedken et al. [41] (see Fig. 8)
Covalent Janus Kinase 3 Inhibitors
233