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ID: ALA1134995

Journal: Bioorg Med Chem Lett

Title: Enhancement of pharmacokinetic properties and in vivo efficacy of benzylidene ketal M(2) muscarinic receptor antagonists via benzamide modification.

Authors: Boyle CD, Vice SF, Campion J, Chackalamannil S, Lankin CM, McCombie SW, Billard W, Binch H, Crosby G, Williams MC, Coffin VL, Cox KA, Grotz DE, Duffy RA, Ruperto V, Lachowicz JE.

Abstract: We previously reported the initial discovery of a novel class of stabilized benzylidene ketal M(2) receptor antagonists. This paper discusses new analogues consisting of benzamide modifications which not only improved M(2) 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 M(2) antagonist, which demonstrated in vivo efficacy and had good bioavailability in multiple species.

CiteXplore: 12419388

DOI: 10.1016/s0960-894x(02)00742-4