N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1), a Novel α1-Adrenoceptor Ligand with an Enhanced in Vitro and in Vivo Profile Relative to Phenylpropanolamine and Midodrine

N-[3-(1H-Imidazol-4-ylmethyl)phenyl]ethanesulfonamide (ABT-866, 1) is a novel α1 agent having the unique profile of α1A (rabbit urethra, EC50 = 0.60 μM) agonism with α1B (rat spleen, pA2 = 5.4) and α1D (rat aorta, pA2 = 6.2) antagonism. An in vivo dog model showed 1 to be more selective for the urethra over the vasculature than A-61603 (2), ST-1059 (3, the active metabolite of midodrine), and phenylpropanolamine (4).