A novel class of allosteric modulators of the muscarinic M2 acetylcholine receptor:: terphenyl derivatives

The allosteric modulation of receptors has become a widely accepted concept in order to enhance the agonist or antagonist binding to a receptor. Alcuronium, characterized by a high allosteric potency and a positive cooperativity at the muscarinic M-2 receptor, was chosen as a template to design a structural novel terphenyl-type of allosteric modulator. The skeleton was build up from 1-bromo-2-methylnaphthalene and 1,4-dibromo-2,5-dimethylbenzene using bis(triphenylphosphine)nickel(II) dichloride as a catalyst. Several amino substituted terphenyls were synthesised and preliminary pharmacological tests were performed. (C) 2003 Elsevier Ltd. All rights reserved.