6-Heteroarylimidazo[1,2-a]pyridines derivatives, their preparation and their therapeutic use for NOT receptor-associated disease treatment.

Abstract

The invention is related to the prepn. of title compds. I [R1 = (un)substituted Ph, naphthyl, heteroaryl, heterocyclyl; Het = 5-6 membered monocyclic heteroaryl ring contg. 1-3 heteroatoms selected from N, O and S; X = 1-3 substituents independently selected from H, halo, alkyl, alkoxy, NH2 and derivs., etc.; R = 1-4 substituents in positions 3, 5, 7 or 8 of the imidazo[1,2-a]pyridine system independently selected from H, halo, alkyl, haloalkyl, alkoxy; R2-4 = independently H, (un)substituted alkyl, aryl] and their acid addn. salts for the prepn. of a medicament for the treatment and the prevention of the diseases in which the NOT receptor is implicated. Thus, cyclization of 2-amino-5-iodopyridine with 2-bromo-1-(4-chlorophenyl)ethanone, Pd-coupling of the iodoimidazopyridine with (5-formylfuran-2-yl)boronic acid, and redn. of the aldehyde gave II. [2-[2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-6-yl]pyridin-4-yl]methanol was evaluated for the in vitro activity on a cell line (N2A) endogenously expressing the murine Nurr1 receptor and stably transfected with the NOT binding response element (NBRE) coupled to the luciferase reporter gene and displayed an EC50 = 4.5 nM. [on SciFinder(R)]