A new family of H3 receptor antagonists based on the natural product Conessine.

Abstract A new family of Histamine H 3 receptor antagonists ( 5a – t ) has been prepared based on the structure of the natural product Conessine, a known H 3 antagonist. Several members of the new series are highly potent and selective binders of rat and human H 3 receptors and display inverse agonism at the human H 3 receptor. Compound 5n exhibited promising rat pharmacokinetic properties and demonstrated functional antagonism of the H 3 receptor in an in-vivo pharmacological model.