Enhancement of pharmacokinetic properties and in vivo efficacy of benzylidene ketal M2 muscarinic receptor antagonists via benzamide modification

We previously reported the initial discovery of a novel class of stabilized benzylidene ketal M2 receptor antagonists. This paper discusses new analogues consisting of benzamide modifications which not only improved M2 receptor affinity and selectivity, but also enhanced the pharmacokinetic properties of the series. These changes led to the discovery of a highly potent and selective M2 antagonist, which demonstrated in vivo efficacy and had good bioavailability in multiple species.