The synthesis of analogues of mecamylamine

Abstract

The anti-hypertensive drug MA (Inversine®) has been investigated for and shown antiaddictive and anti-depressive properties, in both human subjects and animal models. Due to its restrictive synthesis, structure-activity relationship studies (SAR) on MA have been very limited to date. Previous work within the group developed a novel synthetic route to the parent compound which allowed for the selective functionalisation of the 2 and 3 positions. The work herein describes a number of modifications of MA at positions 2,3 and around the amine. Further alterations to the bicyclic framework were investigated, namely functionalisation of positions 5 and 6 and the bridgehead position 7. In addition ring expanded [2.2.2]bicyclic systems were also investigated.