The synthesis of a novel class of piperazine benzamide (reverse amides) targeting the human beta(3)-adrenergic receptor for the treatment of overactive bladder (OAB) is described. The SAR studies directed towards maintaining well established 63 potency and selectivities while improving the overall pharmacokinetic profile in the reverse amide class will be evaluated. The results and consequences associated with functional activity at the norepinephrine transporter (NET) will also be discussed. (C) 2016 Elsevier Ltd. All rights reserved.