The 1,4-dihydroquinolone template is a useful core for designing potent 5-HT1B antagonists. Using a pharmacophore cluster analysis paradigm, new 5-HT1B antagonist scaffolds were designed to improve the in vitro and in vivo profile of these prior scaffolds. Out of this pharmacophore analysis a cyclic urea-based scaffold was designed and several analogs were prepared. This presentation will focus on the process that helped design that scaffold, the chemistry used to prepare those analogs, and the SAR that resulted from this series.