AR binding affinity

The 3,3-diphenylpentane derivatives (35a-d and 36a-d) mentioned above also possess AR-binding affinity [9,32,33]. Concerning the AR-binding activities of the triol derivatives (35a-d), the (5, 5 )-isomers are the eutomers, in contrast to the case of VDR-binding activity, where the (l ,5)-isomers are the eutomers. (5, 5 )-DPP-0123 [(5,5)-35c] shows the most potent activity, with a Ki value of 400 nM. Nevertheless, aU optical isomers of LG190178 (35d) show similar... 

AR-binding affinity, with Ki values of 1000 to 1100 nM, suggesting that the exchanged nitrogen atom(s) interacts with some residue(s) in the ligand-binding... 

Size and shape descriptors confirmed their effectiveness in correlating with the binding affinities. In fact, the most significant QSAR models obtained involved Vdif, in the case of the 5-HT1AR, and Vou, or Vdif f°r the oq-AR ... 

The availability of in vitro binding affinity data on the cloned oq-ARs allowed for the building of subtype specific QSAR models based on noncongeneric series of ligands. 

The most relevant bilinear regression models obtained for the binding affinity of the oq-AR subtypes are the following ... 

Finally, very recently Pallavicini et al., in continuation of a previous study on ortho-monosubstituted compounds, designed and synthesized a series of 2-[(2-phenox-yethyl) aminomethyl]-l,4-benzodioxanes ortho-disubstituted at the phenoxy moiety [99]. The disubstituted analogues were tested for their binding affinities at the three oq-AR subtypes and for the 5-HT1A-R. The affinity values of the new compounds were compared with those of the enantiomers of the 2,6-dimethoxyphenoxy analogue, the well-known oq-AR antagonist WB-4101 (Scheme 8.1), and of the ortho-monosubstituted derivatives. The results suggested some distinctive aspects in the interaction of the phenoxy moiety of monosubstituted and disubstituted compounds with the cqa-AR and the 5-HTiA receptors. A classical (Hansch) QSAR analysis was applied to the whole... 

Some of the effects of glucocorticoids can be attributed to their binding to aldosterone receptors (ARs). Indeed, ARs bind aldosterone and cortisol with similar affinity. A mineralocorticoid effect of cortisol is avoided in some tissues by expression of llE>-hydroxysteroid dehydrogenase type 2, the enzyme responsible for biotransformation to its 11-keto derivative (cortisone), which has minimal affinity for aldosterone receptors. 

Binding affinity data of thiazoles and thiadiazoles at the hA3 AR have been subjected to QSAR analysis (Bhattacharya et al. 2005). This study disclosed the importance of molecular electrostatic potential surface (Wang-Ford charges) in correspondence of atoms C2, C5, C7, X8 and S9 (Fig. 7.6), the last two playing the most important roles. Furthermore, the A3 binding affinity increases with decrease of lipophilicity of the compounds and in the presence of short alkyl chains (Me or Et) at the R position. 

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