Boyle Craig D, Vice Susan F, Campion Jennifer, Chackalamannil Samuel, Lankin Claire M, McCombie Stuart W, Billard William, Binch Herbert, Crosby Gordon, Williams Mary-Cohen, Coffin Vicki L, Cox Kathleen A, Grotz Diane E, Duffy Ruth A, Ruperto Vilma, Lachowicz Jean E
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Bioorg Med Chem Lett. 2002 Dec 2;12(23):3479-82. doi: 10.1016/s0960-894x(02)00742-4.
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.
