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Review
. 2014 Mar;6(4):385-412.
doi: 10.4155/fmc.13.215.

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

Ruben S Vardanyan  1 , Victor J Hruby
Affiliations
Review

Fentanyl-related compounds and derivatives: current status and future prospects for pharmaceutical applications

Ruben S Vardanyan et al. Future Med Chem. 2014 Mar.

Abstract

Fentanyl and its analogs have been mainstays for the treatment of severe to moderate pain for many years. In this review, we outline the structural and corresponding synthetic strategies that have been used to understand the structure-biological activity relationship in fentanyl-related compounds and derivatives and their biological activity profiles. We discuss how changes in the scaffold structure can change biological and pharmacological activities. Finally, recent efforts to design and synthesize novel multivalent ligands that act as mu and delta opioid receptors and NK-1 receptors are discussed.

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Conflict of interest statement

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1
Figure 1
Fentanyl and major fentanyl analogs.
Figure 2
Figure 2
Approaches to the synthesis of fentanyl.
Figure 3
Figure 3
Modifications of the structure of fentanyl.
Figure 4
Figure 4
Synthesis of perhydroazepine analogs of fentanyl.
Figure 5
Figure 5
Methyl-substituted fentanyls.
Figure 6
Figure 6
Synthesis of 4-aryl-fentanyl analogs.
Figure 7
Figure 7
Synthesis of carfentanyl, alfentanil sufentanil, R30490, and their analogs.
Figure 8
Figure 8
Alternative synthesis of 4-acyl- fentanyls from corresponding acids.
Figure 9
Figure 9
Synthesis of 4-acyloxymethyl- fentanyls.
Figure 10
Figure 10
Examples of ‘ring-closed’ analogs of fentanyl.
Figure 11
Figure 11
One more example of ‘ring-closed’ analogs of fentanyl – indolylpiperidines.
Figure 12
Figure 12
Synthesis of series of pyridoindoles a benzo[a]-quinolizidine derivatives of fentanyl.
Figure 13
Figure 13
Synthesis of isothiocyanate derivatives of fentanyl.
Figure 14
Figure 14
Replacement of 2-arylethylsubstituents at piperidine ring.
Figure 15
Figure 15
Bivalent ligands based on fentanyl.
Figure 16
Figure 16
Functionalized fentanyls for the synthesis of bivalent ligands.
Figure 17
Figure 17
Newly created bivalent ligands based on fentanyl.
Figure 18
Figure 18
Attempts to synthesize fentanyl/adjuvant bivalent compounds.
Figure 19
Figure 19
One other attempt to synthesize fentanyl/δ-agonist bivalent compounds.
Figure 20
Figure 20
Phenylethyl moiety present in all classes of opioids.
See this image and copyright information in PMC

References

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