Opioid analogues structure activity relationship

An examination of the structure-activity relationship (SAR) of a series of enkephalin analogues and morphine derivatives in competing with the binding of radioisotope labeled DADLE and FK 33-824 or opiates revealed that DADLE binds to an opioid receptor selective to Leu-enkephalin and its analogues. In contrast, FK 33-824, morphine, or naloxone binds to opioid receptors with selectivity in favor of morphine and derivatives simi-... 

The bioactive conformation is consistent with the farmacoforic points that are identified through structure activity relationship studies (SAR). SAR studies include the synthesis of many peptide and/or non peptide analogues displaying selectivity for one or another of the receptors and their pharmacologically defined subtypes [19] such as delta 1- and delta2-opioid receprtor subtypes [20]. 

Due to their high selectivity, DER and DEL were the basis for an extensive structure activity relationship study aimed to understand the essential requisites of p. and 8 activity. More than 200 analogues of DER and DEL C were synthesized, and the role of each amino acid in binding to p and 8 receptors and bioactivity was defined [21-31]. New synthetic products were prepared such as oxymorphindole and related derivatives [32], and (+)-4-[(alfa R)-alfa-((2S,5R)-4-allyl-2.5-dimethyl-l-piperazin-yl)-3-methoxy-benzyl]-N, diethylbenzamide [33]. These products are under investigation for their clinical relevance and provide potential nonpeptide ligands for studies on delta-opioid-receptor. 

---