Yohimbine dimers exhibiting binding selectivities for human α2a- versus α2b-adrenergic receptors

A series of yohimbine dimers was prepared and evaluated at the human α2a- and α2b-adrenergic receptors (ARs) expressed in Chinese hamster ovary (CHO) cells. All dimers display higher binding selectivities for α2a versus α2b subtype than yohimbine, and four compounds (3d, 3e, 3g and 3i) represent the most potent and α2a- versus α2b-AR selective ligands identified so far. Scheme 1.