In-vitro investigation of oxazol and urea analogues of morphinan at opioid receptors

A series of 2-amino-oxazole (7 and 8) analogs and 2-one-oxazole analogs (9 and 10) were synthesized from cyclorphan (1) or butorphan (2) and evaluated in-vitro by their binding affinity at μ, δ, and κ opioid receptors and compared with their 2-aminothiozole analogs 5 and 6. Ligands 7–10 showed decreased affinities at κ and μ receptors. Urea analogs (11–14) were also prepared from 2-aminocyclorphan (3) or 2-aminobutorphan (4) and evaluated in-vitro by their binding affinity at μ, δ, and κ opioid receptors. The urea derived opioids retained their affinities at μ receptors while showing increased affinities at δ receptors and decreased affinities at κ receptors. Functional activities of these compounds were measured in the [35S]GTPγS binding assay, illustrating that all of these ligands were κ agonists. At the μ receptor, compounds 11 and 12 were μ agonist/antagonists.

A series of 2-amino-oxazole and 2-one-oxazole analogs and ureas were synthesized and evaluated in-vitro by their binding affinity at opioid receptors. The orientation of 2′-amino group in the oxazole and thiozole series contributes to their binding affinity.Figure optionsDownload as PowerPoint slide