Info

[137]

"Partial effect reported (SA/TF max <80%; RT max decrease <4°C).

"Partial effect reported (SA/TF max <80%; RT max decrease <4°C).

Melvin et al. [136] have shown that the positioning of the southern aliphatic hydroxyl group is critical for optimal binding. The constrained analogue of (193), (-)-CP 55,244 (195) showed very high CB1 binding affinity and complete enantioselectivity. Conformational studies with diastereoiso-mers of (195) have suggested that the ability to form an intramolecular hydrogen bond between the phenolic hydroxyl group and the southern aliphatic hydroxyl group may be important for receptor binding [138]. However, molecular docking of these compounds in a homology model based on the bovine rhodopsin X-ray crystal structure has suggested that these two hydroxyl groups could form intermolecular hydrogen bonds with different residues in the receptor-binding site [139].

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