Cyclic amine sulfonamides as linkers in the design and synthesis of novel human beta(3) adrenergic receptor agonists.

Piperidine, pyrrolidine, and azetidine sulfonamides were examined as linkers in designing novel human beta(3) adrenergic receptor (beta(3)-AR) agonists. The azetidine derivative 37, and piperidine derivatives 7, 8, and 13 were found to be potent beta(3)-AR agonists and have good selectivity against beta(1)- and beta(2)-AR.

Novel substituted 4-aminomethylpiperidines as potent and selective human beta3-agonists. Part 2: arylethanolaminomethylpiperidines.

The synthesis and SAR of a series of beta3 adrenoreceptor agonists based on a novel template derived from 4-aminomethylpiperidine coupled with a common pharmacophore, arylethylamine, is described. This combination led to the identification of human beta3 adrenoreceptor agonists with in vivo activity in a transgenic mouse model.

Novel substituted 4-aminomethylpiperidines as potent and selective human beta3-agonists. Part 1: aryloxypropanolaminomethylpiperidines.

The synthesis and SAR of a series of human beta3 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 beta3-AR (EC50=49 nM, IA=1.1), and in vivo active in a transgenic mouse model.