α1-Adrenergic receptors (ARs), as the crucial members of G protein-coupled receptors (GPCRs), draw more attention fiom medicinal chemists because they mediate a number of physiological responses of the sympathetic nervous system.So far α1-ARs have at least three major subtypes, α1A, α1B and α1D, based on differences on their intrinsic affinities for selective competitive antagonists and an irreversible antagonist.However, to date it is strenuous either to establish the distribution of each α1-adrenoceptor subtype in various organs and tissues, or to define the functional response mediated by each one in the different species.Fortunately, in recent years, with the rapid expansion of fluorescent techniques for studying the ligand-receptor interaction, the medicinal chemists apply themselves to finding the novel fluorescent ligands for tagging and visualizing the receptors to obtain the pharmacological information.Therefore, herein we well design and synthesize the small-molecule α1-adrenergic receptors fluorescent probes by using QSAR, pharmacophore, homology modeling and molecular docking, as depicted in Figure 1, which mainly contain two parts: the pharmacophore that can be bound to α1-adrenergic receptors and the fluorophore that can be used to make the receptors visualization.And if the α1-adrenergic receptors can be tagged by the small-molecule α1-adrenergic receptors, it is obvious that these small-molecule fluorescent probes will be useful for studying α1-adrenergic receptors.