In:
ChemMedChem, Wiley, Vol. 9, No. 4 ( 2014-04), p. 752-761
Abstract:
Classical drug design and development rely mostly on affinity‐ or potency‐driven structure–activity relationships (SAR). Thus far, a given compound’s binding kinetics have been largely ignored, the importance of which is now being increasingly recognized. In the present study, we performed an extensive structure–kinetics relationship (SKR) study in addition to a traditional SAR analysis at the adenosine A 2A receptor (A 2A R). The ensemble of 24 A 2A R compounds, all triazolotriazine derivatives resembling the prototypic antagonist ZM241385 (4‐(2‐((7‐amino‐2‐(furan‐2‐yl)‐[1,2,4]triazolo[1,5‐ a ][1,3,5] triazin‐5‐yl)amino)ethyl)phenol), displayed only minor differences in affinity, although they varied substantially in their dissociation rates from the receptor. We believe that such a combination of SKR and SAR analyses, as we have done with the A 2A R, will have general importance for the superfamily of G protein‐coupled receptors, as it can serve as a new strategy to tailor the interaction between ligand and receptor.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.201300474
Language:
English
Publisher:
Wiley
Publication Date:
2014
detail.hit.zdb_id:
2209649-8
SSG:
15,3
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