Preparation of imidazopyridine derivatives as therapeutic JAK inhibitors.

Abstract

New imidazopyridine derivs. having the chem. structure of formula I are disclosed; as well as process for their prepn., pharmaceutical compns. comprising them and their use in therapy as inhibitors of Janus kinases (JAK). For I, m = 0-3; Z is O or (un)substituted NH; X and Y independently are N or (un)substituted CH, wherein at least one of X and Y is N; R1-R4, R8, and R9 are independently H, halo, CN, linear or branched C1-6 alkyl, etc.; R6 and R7 are independently H or (un)substituted linear or branched C1-6 alkyl group. Example compd. II, prepd. from intermediate 3-(4-hydroxypyrimidin-2-yl)imidazo[1,2-a]pyridine-6-carbonitrile and (S)-L-phenylethylamine, had IC50 values <0.1 μM for JAK3 and JAK2 and an IC50 between 0.1 μM and 1 μM for JAK1 in in vitro assays. [on SciFinder(R)]