Synthesis and biological evaluation of novel imidazole-containing macrocycles

A new family of compounds made of a 5-aryl-1H-imidazole motif included in a macrocycle has been designed and synthesized. The synthesis of the imidazole core makes use of our previously developed method for the regioselective preparation of 1,2,5-trisubstituted imidazoles while the construction of the macrocycle is based on a three steps sequence: SNAr, Suzuki coupling, and RCM reaction. Biological evaluation of synthesized imidazole-containing macrocycles revealed that they display actual binding activity toward A3 adenosine (h) receptor, dopamine D1 (h) receptor, chloride channel (GABA-gated), and choline transporter (h) CHT1.