Fentanyl affinity labels

Essawi, M.Y.H. Fentanyl analogues with a modified propanamido group as potential affinity labels Synthesis and in vivo activity, Pharmazie 1999, 54, 307-308. 

Derivatives of fentanyl and sufentanil with chemo- and photoaffinity functionalities attached to the anilido nitrogen (e.g., NCOCH2Br, NCOCH=N2) have been reported, but affinity labeling experiments performed with theses compounds on brain tissue met with little success. Some of the compounds, notably the diazoacetyl analog of cis 3-methylfentanyl, displayed high binding affinities.(60)... 

Affinity label derivatives of fentanyl and (+)-cis-3-methylfentanyl FIT (198, 461) and SUPERFIT (458), which have an isothiocyanate group on the phenyl ring of the piperidino substituent, have been prepared. Unlike the reversible parent compounds, which are /x agonists, these affinity labels irreversibly bind to 6 receptors. These compounds are discussed further in Section 5.11 on affinity labels. 

Rice and co workers prepared a variety of affinity labels on the basis of the structures of eto-nitazine, fentanyl, and oripavine (Fig. 7.39) (198, 461). The etonitazene derivative BIT (196) selectively inactivates /a receptors, whereas the fentanyl derivative FIT (fentanyl isothiocyanate, 197) and the oripavine derivative FAO (fumaramido oripavine, 200) selectively inactivate 6 receptors. The selective alkylation of S receptors by FIT, which is a derivative of the p-selective ligand fentanyl. 

Examples of important affinity labeling agents are P-CNA, which because of its highly reactive 2-chloroethylamine electrophilic group irreversibility binds to all three opioid receptor types (50). The structurally related compound p-FNA has a less reactive fumaramide electrophilic group and reacts irreversibly with only p receptors (51). Derivatives of the fentanyl series, FIT and... 

---