ArAR antagonist

HY) as possible features. Two additional constraints were set (i) because of the molecular flexibility and functional complexity of the training set, only pharmacophores containing five features should be considered and (ii) the program was forced to include a positive ionizable feature in the composition of hypotheses, on the basis of the literature reporting a basic atom (usually a nitrogen) as a critical structural determinant for arAR antagonistic activity. 

Fig. 12.1 Compound 5 (with the highest a,-AR affinity among the training set compounds) superposed on the pharmaco-phoric model for arAR antagonists.

Modeling the arAR Subtype Selectivities of Different Classes of Antagonists 171... 

Fig. 12.3 Comparison between the first six-feature pharmaco-phoric model for a1(j-AR antagonists and the improved five-feature pharmacophoric model for the same arAR subtype antagonists.

We have observed, in endothelial cells of mouse carotid artery, BODIPY FL-prazosin binding that is inhibited by the a2-antagonist rauwolscine. The presence of o -ARs on vascular endothelium is not new (43 45), but its visualization is. In addition, a report has suggested the presence of a1D-ARs on the endothelium (46), so as methodology improves, we can anticipate visualization of arARs on endothelium. 

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