Novel substituted 4-aminomethylpiperidines as potent and selective human β3-agonists. Part 1: aryloxypropanolaminomethylpiperidines

The synthesis and SAR of a series of human β3 adrenoreceptor agonists based on a template derived from a common pharmacophore coupled with 4-aminomethylpiperidine is described. Potent and selective agents were identified such as 26 that was in vitro active in CHO cells expressing human β3-AR (EC50=49 nM, IA=1.1), and in vivo active in a transgenic mouse model.