Lipophilic pocket

From the molecular modeling analyses of isoprenoid-substituted phenols that did not showed binding affinity for the estrogen receptor, it was indicated that the binding sites at C-3 and C-17 of 17P-estradiol are rigid, but the lipophilic pocket near C-4-C-7 is flexible. 

Figure 11. The model developed in our laboratory suggests two distinct lipophilic pockets available for antagonists binding (indicated by 1 and 2). (See text for more details). 

The isopropylidene derivative of 318 generally improved affinity toward Aj receptors. Its affinity with the corresponding 2-phenyl-9-benzyl-8-azaadenines confirmed the more complex arrangement of 8-azaadenines inside Aj receptors, in which three lipophilic pockets are present. The selectivity of the N-6-substituted compound was higher than that of the N-6-unsubstituted compounds (95FA13). 

For these later two examples, the substitution of the inhibitor NH2 with NHPh, which places the aryl group in this lipophilic pocket, affords a 10-fold increase in potency. 

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