Author/Authors :
Craig D. Boyle، نويسنده , , Susan F. Vice، نويسنده , , Jennifer Campion، نويسنده , , Samuel Chackalamannil، نويسنده , , Claire M. Lankin، نويسنده , , Stuart W. McCombie، نويسنده , , William Billard، نويسنده , , Herbert Binch III، نويسنده , , Gordon Crosby، نويسنده , , Mary Cohen-Williams، نويسنده , , Vicki L. Coffin، نويسنده , , Kathleen A. Cox، نويسنده , , Diane E. Grotz، نويسنده , , Ruth A. Duffy، نويسنده , , Vilma Ruperto، نويسنده , , Jean E. Lachowicz، نويسنده ,
Abstract :
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.
